Hip Fracture, Frailty, Sarcopenia
Conditions
Brief summary
This study is a randomized controlled double-blinded multi-center clinical trial enrolling female hip fracture patients who are 65 and older. It will compare the effects of six months of supervised exercise training combined with daily topical testosterone gel, to six months of supervised exercise and inactive gel, and to Enhanced Usual Care. The randomization protocol is that for every nine participants randomized, 4 will be assigned to the topical testosterone gel and supervised exercise training group; 4 will be assigned to topical inactive gel and supervised exercise training group; and 1 will be assigned to the enhanced usual care group. All participants will receive nutritional counseling, and calcium and vitamin D supplements.
Detailed description
Hip fractures are common among older women and can have a devastating impact on their ability to remain independent. A clinically important functional decline and failure to recover following a hip fracture has been documented as late as a year after the fracture, even among women who were functioning at high levels before the event. Age-associated androgen deficiency in women contributes to deficits in muscle mass, strength and power that are common in this patient population before the fracture, and are exacerbated afterward. A pilot study of testosterone (T) supplementation in elderly female hip fracture patients has demonstrated the feasibility of T treatment in this population, and showed gains in lean body mass (LBM) and muscle strength with active drug, compared to placebo. The benefits of exercise in restoring muscle strength and physical function after a hip fracture have been documented. However, it remains unclear whether T treatment can augment the effects of exercise on mobility and patient-reported function after hip fracture. The STEP-HI study is a 3-group, multi-center, randomized, placebo-controlled, double-blinded, parallel group clinical trial in older female hip fracture patients. Between 120 and 168 female hip fracture patients, age 65 years and older, will be randomized from multiple clinical sites in the USA, using objective screening criteria for T deficiency (serum total testosterone level \< 60 ng/dL) and physical frailty (Modified Physical Performance Test (PPT) Score of 12-28). The primary study aim is to compare supervised exercise training (EX) with inactive (placebo) gel (EX+P) and EX combined with T therapy (EX+T), to ascertain the incremental impact of adding T to EX in older adult women with a recent hip fracture. The study team will carefully monitor testosterone levels, adverse events, biochemical parameters, and factors related to adherence to the interventions. Information from this study has the potential to alter treatment of hip fracture in older women, a problem that contributes to significant morbidity and mortality, and has a large public health impact. The STEP-HI study is highly aligned with NIA's mission of identifying interventions that target common geriatric conditions and improve treatment options for older adults with multiple morbidities or risk factors.
Interventions
DRUGTestosterone
Topical testosterone gel 1%
DRUGPlacebo gel
Inactive skin gel
BEHAVIORALSupervised exercise training
Multicomponent exercise program focused primarily on progressive resistance exercise training
BEHAVIORALHome exercise program
Flexibility exercises performed at home 3 times per week and reviewed by study staff once a month.
BEHAVIORALHealth Education Modules
30-40 minute presentations conducted by study staff for participants focused on health concerns unrelated to exercise.
Sponsors
University of Maryland, Baltimore
University of Colorado, Denver
The University of Texas Medical Branch, Galveston
Johns Hopkins University
Harvard University
University of Connecticut
University of Utah
University of Pittsburgh Medical Center
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants, investigators, and study staff conducting the interventions will be aware of the exercise group assignment. A Blinded Outcomes Assessor will be masked to study group assignment. Only the study pharmacist, an unblinded study physician, and Data Coordinating Center staff will be unblinded to gel treatment assignment.
Eligibility
Sex/Gender
FEMALE
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female 65 years and older. * Surgical repair of a non-pathologic fracture of the proximal femur (Including: femoral neck or intracapsular, intertrochanteric, and subtrochanteric fractures) with a surgical repair date that is within 24 weeks at randomization. If a revision of such a fracture is performed due to failure of the repair, that surgery revision date may be used to calculate the time frame for the screening and randomization dates. * Community-dwelling or in assisted living prior to the hip fracture event. * Functional impairment at the time of screening, defined as a modified Physical Performance Score (mPPT) of 12-28. * Serum total testosterone level \<60 ng/dL.
Exclusion criteria
* Cognitive impairment or dementia of severity sufficient to interfere with ability to fully participate in the study or provide one's own informed consent, or a score of 11 or greater on the Short Blessed Test of Orientation, Memory and Concentration. * Residence too far from research center (specific distance to be determined by each site) or planned travel greater than 2 weeks within the next 9 months. * Anticipated to be permanently living in a nursing home at the time of randomization. * Use of progestin or androgen containing compound within the previous 6 months. * Treatment with systemic corticosteroids (daily dose \> 5 mg prednisone or equivalent) for at least 90 days within the previous 12 months. * Visual or hearing impairments that interfere with following directions for research procedures. * Active or unstable cardiopulmonary disease (recent myocardial infarction, unstable angina, class III or IV Congestive Heart Failure) within prior 6 months, which would limit full participation in the study. * Respiratory disease requiring chronic continuous oxygen therapy, or oxygen therapy during walking or exercise, which would limit full participation in this study. * History of idiopathic deep venous thrombosis or pulmonary embolus (i.e., not related to period or immobilization or surgery), any pulmonary embolus less than 12 weeks prior to the first screening visit, recurrent or multiple venous thrombi; history of a hypercoagulable state such as Factor V Leiden thrombophilia. * Musculoskeletal or neurological conditions that limit participation in this study, could be made worse by exercise training, or not expected to improve with exercise. * Lower extremity amputation other than toes. * Severe lower extremity pain or ulceration that could limit full participation in this study. * History of: a) Breast, ovarian, endometrial or cervical cancer with diagnosis within the previous 10 years; b) Breast, ovarian, endometrial, or cervical cancer of Stage 2 or higher. * History of HIV or active viral hepatitis. * End Stage Renal Disease on dialysis or Glomerular Filtration Rate (GFR)\<15 ml/min. * Allergy to gel components. * Recent history of alcohol or substance abuse, or current alcohol intake of ≥ 10 drinks/week. * Planned joint surgery during the intervention period. * Participation in another research study that in the site investigator's judgement could interfere or conflict with STEP-HI research assessments or interventions. * Current use of aldactone, flutamide or leflunomide. * Geriatric Depression Scale (GDS) score ≥ 12 at the screening assessment. * Uncontrolled hypertension, defined as a systolic BP \> 160 mmHg or diastolic BP \> 95 mmHg, on at least two occasions. * Elevated liver transaminase or alkaline phosphatase levels ≥ 2.5 times above normal range. * Erythrocytosis defined as hematocrit \> 51% (all sites but University of Utah) or ≥ 52% at University of Colorado - Denver and University of Utah sites. * Severe anemia defined as Hgb \< 7gm/dL. * Uncontrolled diabetes defined as HgbA1C \> 10%. * Untreated or unstable thyroid disease, with serum Thyroid-stimulating Hormone (TSH) level ≥ 10 milli-international units per liter (mIU/L) or TSH level ≤ 0.4 mIU/L. Levels outside of the given range require site physician documentation addressing treatment or absence of thyroid disease and approval by the Central Coordinating Center (CCC). * Site investigator's judgement that the participant would not be able to complete research procedures or interventions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Six Minute Walk Distance | Baseline to 6 months | Walking endurance was measured using a 6-Minute Walk Distance. Participants were asked to walk back and forth on a measured path marked clearly at both ends for turning purposes, while being told when each minute has passed, and receiving verbal encouragement every 60 seconds. Total distance was measured in meters with higher distances equating to higher walking endurance. Each individual participant distance from Baseline was subtracted from Month 6 to represent change over the length of the study. Higher positive values represent more improvement in walking distance. In addition to the primary analysis (unadjusted baseline to 6 month comparison), statistical contracts were evaluated to determine if there was significant between-group differences in the change from baseline to 3 months and additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Appendicular Lean Body Mass | Baseline to 6 months | Lean body mass of the arms and legs, measured by dual x-ray absorptiometry (DXA). Baseline DXA scans were completed prior to the first administration of study drug. All scans were completed prior to exercise or 1-RM measurements if scheduled for the same day. DXA scans were reviewed for quality control, proper positioning, and artifacts centrally. Each individual participant measure from Baseline was subtracted from Month 6 to represent change over the length of the study. Higher positive values represent more gains in appendicular lean body mass. Per the protocol: In addition to the primary analysis (unadjusted baseline to 6 month comparison), additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline. DXA was not performed at 3 months. |
| Change in 1-repetition Maximum (1-RM) Leg Press Strength | Baseline to 6 months | Muscle strength measured as the maximal amount of weight that the participant was able to lift for one repetition (1-RM). The 1-RM is defined as the greatest resistance that could be overcome through a defined range of motion using proper techniques. Subjects were asked to move against progressively heavier resistance loads until a repetition failure was achieved. Each individual participant measure from Baseline was subtracted from Month 6 to represent change over the length of the study. Higher positive values represent the increased ability to lift more weight. Per the protocol: In addition to the primary analysis (unadjusted baseline to 6 month comparison), statistical contracts were evaluated to determine if there was significant between-group differences in the change from baseline to 3 months and additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline. |
| Change in Total Modified Physical Performance Test (mPPT) Score | Baseline to 6 months | A modified version of the Physical Performance Test (mPPT) was used to measure physical function. Participants were asked to complete 9 standardized tasks (book lift, putting on a lab coat, picking up a penny from the floor, standing balance, standing up five times from a 16-inch chair, 50 foot walk including a turn, 360 degree turn, stair climb for 10 steps, and climbing 2 additional flights of steps) for a total score ranging from 0 (significant impairment) to 36 (excellent functioning). Each individual participant score from Baseline was subtracted from Month 6 to represent change over the length of the study. Higher positive values represent more improvement in physical functioning. |
| Change in Short Physical Performance Battery (SPPB) Score | Baseline to 6 months | The Short Physical Performance Battery (SPPB) is a well validated objective physical performance measure used to identify risk for disability. The SPPB consists of: chair rise, progressive Romberg balance, and 4 meter gait speed. Each task was scored (0-4) with a total range of 0-12. Participants who score 0 are unable to complete the tasks and participants with higher scores are considered to have higher functional mobility. Each individual participant score from Baseline was subtracted from Month 6 to represent change over the length of the study. Higher positive values represent more improvement in physical performance. In addition to the primary analysis (unadjusted baseline to 6 month comparison), statistical contracts were evaluated to determine if there was significant between-group differences in the change from baseline to 3 months and additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline. |
| Change in Total Lean Body Mass | Baseline to 6 months | Total lean body mass measured by dual x-ray absorptiometry (DXA). Baseline DXA scans were completed prior to the first administration of study drug. All scans were completed prior to exercise or 1-RM measurements if scheduled for the same day. DXA scans were reviewed for quality control, proper positioning, and artifacts centrally. Each individual participant measure from Baseline was subtracted from Month 6 to represent change over the length of the study. Higher positive values represent more gains in total lean body mass. Per the protocol: In addition to the primary analysis (unadjusted baseline to 6 month comparison), additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline. DXA was not performed at 3 months. |
| Change in Functional Status Questionnaire (FSQ) Total Score | Baseline to 6 months | The Functional Status Questionnaire (FSQ) is a self-reported measure asking about the amount of difficulty a participant experienced when performing daily tasks in the previous 4 weeks. There are a total of 6 subscales, but only the basic ADL and Intermediate ADL were used in the STEP-HI study for a total of 9 items. Scores range from 0 (high amount of difficulty completing tasks) to 36 (no difficulty completing tasks). Per the protocol: In addition to the primary analysis (unadjusted baseline to 6 month comparison), statistical contracts were evaluated to determine if there was significant between-group differences in the change from baseline to 3 months and additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline. |
| Change in Hip Rating Questionnaire Total Score | Baseline to 6 months | The Hip Rating Questionnaire (HRQ) Standardized is a 14-item scale with weighted questions regarding quality of life (pain level and ability to walk) and function (ability to use stairs, put on socks/shoes, use public transportation, bathe, shop, do housework, and get in and out of a chair/bed) related to the hip fracture event. The scale scores range from 16 to 100. Higher scores are associated with less pain, higher function, and better quality of life. Per the protocol: In addition to the primary analysis (unadjusted baseline to 6 month comparison), statistical contracts were evaluated to determine if there was significant between-group differences in the change from baseline to 3 months and additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline. |
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Baseline to 6 months | Patient-Reported Outcomes Measurement Information System (PROMIS®) Global Health instrument is a 10 item self report questionnaire used to measure overall quality of life using 2 summary scores: Physical and Mental Health. Each summary score is standardized to the general population, with the average T-score for the US population being 50 and standard deviation of 10. Each individual participant T-score from Baseline was subtracted from Month 6 T-score to represent change over the length of the study. Higher scores represent larger increases in Physical and Mental Health. Per the protocol: In addition to the primary analysis (unadjusted baseline to 6 month comparison), statistical contracts were evaluated to determine if there was significant between-group differences in the change from baseline to 3 months and additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline. |
| Change in Bone Mineral Density (BMD) of the Non-fractured Proximal Femur | Baseline to 6 months | Bone mineral density (BMD) measured by dual x-ray absorptiometry (DXA) of the non-fractured proximal femur in participants without hardware in the contralateral hip. Baseline DXA scans were completed prior to the first administration of study drug. All scans were completed prior to exercise or 1-RM measurements if scheduled for the same day. DXA scans were reviewed for quality control, proper positioning, and artifacts centrally. Per the protocol: In addition to the primary analysis (unadjusted baseline to 6 month comparison), additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline. DXA was not performed at 3 months. |
| Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | Baseline to 6 months | The OARS Multidimensional Functional Assessment Questionnaire Activities of Daily Living (ADL) is a standardized, valid and reliable, self-report questionnaire used to determine the effect of services on the functional status of older adults by asking respondents about their ability to perform ADLS on 2 subscales: Basic (BADL) and Instrumental (IADL). Both subscales are scored from 0 (significant impairment) to 14 (excellent functioning). The individual participant score from Baseline was subtracted from Month 6 to represent change over the length of the study. Higher positive values represent more improvement in functioning. In addition to the primary analysis (unadjusted baseline to 6 month comparison), statistical contracts were evaluated to determine if there was significant between-group differences in the change from baseline to 3 months and additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline. |
Countries
United States
Participant flow
Recruitment details
Between August 2018 and February 2023, participants identified from hospital records or referred from physicians/rehabilitation staff at 8 academic medical centers, were approached 6-24 weeks following hip repair surgery. If eligible by chart review, participants were pre-screened, consented for full study, screened, and completed baseline assessments, prior to randomization. The first participant was randomized in March 2019 and the final participant randomized in February 2023.
Pre-assignment details
4695 charts were reviewed. 907 were eligible by chart review and 344 agreed to complete the pre-screening questionnaire. Of those, 28 failed, another 42 were deemed ineligible after further review, 7 refused to review the consent, and 60 refused consent. Leaving 207 who consented for screening, of which 12 refused to continue to screening visit and 10 were found ineligible prior to screening. 185 screened, of whom 32 screen failed, 7 refused after screening, and 17 were ineligible to randomize.
Participants by arm
| Arm | Count |
|---|---|
| Exercise + Testosterone (EX + T) Supervised exercise training 2 times per week and topical testosterone 1% gel (12.5 mg per pump depression), both for six months duration.
Testosterone: Topical testosterone gel 1%
Supervised exercise training: Multicomponent exercise program focused primarily on progressive resistance exercise training | 55 |
| Exercise + Placebo (EX + P) Supervised exercise training 2 times per week and placebo gel daily, both for six months duration.
Placebo gel: Inactive skin gel
Supervised exercise training: Multicomponent exercise program focused primarily on progressive resistance exercise training | 54 |
| Enhanced Usual Care (EUC) Home exercise program 3 times per week and monthly health education modules, both for six months duration.
Home exercise program: Flexibility exercises performed at home 3 times per week and reviewed by study staff once a month.
Health Education Modules: 30-40 minute presentations conducted by study staff for participants focused on health concerns unrelated to exercise. | 20 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Exercise + Testosterone (EX + T) | Total | Enhanced Usual Care (EUC) | Exercise + Placebo (EX + P) |
|---|---|---|---|---|
| Age, Continuous | 79.42 years STANDARD_DEVIATION 9.08 | 79.49 years STANDARD_DEVIATION 8.43 | 82.98 years STANDARD_DEVIATION 8.39 | 78.28 years STANDARD_DEVIATION 7.52 |
| Appendicular lean body mass | 15650.59 Grams STANDARD_DEVIATION 3045.8 | 15822.42 Grams STANDARD_DEVIATION 2965.91 | 15070.01 Grams STANDARD_DEVIATION 2279.41 | 16276.07 Grams STANDARD_DEVIATION 3078.32 |
| Body mass index (BMI) | 25.61 Kilograms/meters ^2 (kg/m^2) STANDARD_DEVIATION 5.49 | 25.96 Kilograms/meters ^2 (kg/m^2) STANDARD_DEVIATION 5.06 | 24.43 Kilograms/meters ^2 (kg/m^2) STANDARD_DEVIATION 3.36 | 26.89 Kilograms/meters ^2 (kg/m^2) STANDARD_DEVIATION 5.02 |
| Bone mineral density (BMD) of non-fractured proximal femur | 0.71 Grams/centimeters^2 (g/cm^2) STANDARD_DEVIATION 0.12 | 0.72 Grams/centimeters^2 (g/cm^2) STANDARD_DEVIATION 0.12 | 0.71 Grams/centimeters^2 (g/cm^2) STANDARD_DEVIATION 0.12 | 0.73 Grams/centimeters^2 (g/cm^2) STANDARD_DEVIATION 0.12 |
| Co-morbidity count | 5.20 units on a scale STANDARD_DEVIATION 3.09 | 5.27 units on a scale STANDARD_DEVIATION 2.86 | 5.85 units on a scale STANDARD_DEVIATION 3.17 | 5.13 units on a scale STANDARD_DEVIATION 2.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 5 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 54 Participants | 120 Participants | 18 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 1 Participants | 3 Participants |
| Functional Status Questionnaire (FSQ) | 23.16 units on a scale STANDARD_DEVIATION 4.8 | 22.30 units on a scale STANDARD_DEVIATION 4.97 | 21.30 units on a scale STANDARD_DEVIATION 5.15 | 21.80 units on a scale STANDARD_DEVIATION 5.03 |
| Geriatric Depression Scale (GDS) | 1.84 unites on a scale STANDARD_DEVIATION 1.75 | 2.29 unites on a scale STANDARD_DEVIATION 2.06 | 3.15 unites on a scale STANDARD_DEVIATION 2.62 | 2.43 unites on a scale STANDARD_DEVIATION 2.04 |
| Hand grip strength - left hand | 15.27 Kilograms (kg) STANDARD_DEVIATION 6.04 | 15.65 Kilograms (kg) STANDARD_DEVIATION 5.68 | 15.82 Kilograms (kg) STANDARD_DEVIATION 5.45 | 15.96 Kilograms (kg) STANDARD_DEVIATION 5.49 |
| Hand grip strength - right hand | 16.45 Kilograms (kg) STANDARD_DEVIATION 5.84 | 16.95 Kilograms (kg) STANDARD_DEVIATION 5.84 | 16.95 Kilograms (kg) STANDARD_DEVIATION 5.69 | 17.44 Kilograms (kg) STANDARD_DEVIATION 5.95 |
| Hip Rating Questionnaire (HRQ) | 72.06 units on a scale STANDARD_DEVIATION 12.36 | 70.82 units on a scale STANDARD_DEVIATION 11.42 | 70.89 units on a scale STANDARD_DEVIATION 11.87 | 69.54 units on a scale STANDARD_DEVIATION 10.227 |
| History of Lung Disease lung disease | 4 Participants | 11 Participants | 4 Participants | 3 Participants |
| History of Lung Disease No lung disease | 51 Participants | 118 Participants | 16 Participants | 51 Participants |
| Leg Press 1-Repetition Maximum | 97.12 Pounds STANDARD_DEVIATION 53.86 | 91.06 Pounds STANDARD_DEVIATION 49.09 | 88.61 Pounds STANDARD_DEVIATION 55.16 | 85.41 Pounds STANDARD_DEVIATION 40.97 |
| Modified Physical Performance (mPPT) Score | 20.85 units on a scale STANDARD_DEVIATION 6.73 | 20.14 units on a scale STANDARD_DEVIATION 6.85 | 17.55 units on a scale STANDARD_DEVIATION 6.95 | 20.37 units on a scale STANDARD_DEVIATION 6.84 |
| Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire Basic Activities of Daily Living (BADL) | 12.15 units on a scale STANDARD_DEVIATION 1.67 | 12.07 units on a scale STANDARD_DEVIATION 1.82 | 12.05 units on a scale STANDARD_DEVIATION 1.76 | 12.0 units on a scale STANDARD_DEVIATION 2.01 |
| Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire Instrumental Activities of Daily Living (IADL) | 11.51 units on a scale STANDARD_DEVIATION 2.43 | 11.39 units on a scale STANDARD_DEVIATION 2.37 | 11.35 units on a scale STANDARD_DEVIATION 1.93 | 11.28 units on a scale STANDARD_DEVIATION 2.48 |
| Patient-Reported Outcomes Measurement Information System (PROMIS®) Global Health Mental Health T-score | 51.75 T-score STANDARD_DEVIATION 6.2 | 50.84 T-score STANDARD_DEVIATION 6.67 | 47.75 T-score STANDARD_DEVIATION 7.99 | 51.07 T-score STANDARD_DEVIATION 6.39 |
| Patient-Reported Outcomes Measurement Information System (PROMIS®) Global Health Physical Health T-score | 48.29 T-score STANDARD_DEVIATION 6.35 | 47.00 T-score STANDARD_DEVIATION 6.42 | 45.59 T-score STANDARD_DEVIATION 5.99 | 46.21 T-score STANDARD_DEVIATION 6.51 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 52 Participants | 120 Participants | 19 Participants | 49 Participants |
| Region of Enrollment United States | 55 participants | 129 participants | 20 participants | 54 participants |
| Serum Testosterone Level (Free) | 0.24 nanograms per deciliter (ng/dL) STANDARD_DEVIATION 0.18 | 0.22 nanograms per deciliter (ng/dL) STANDARD_DEVIATION 0.15 | 0.17 nanograms per deciliter (ng/dL) STANDARD_DEVIATION 0.09 | 0.25 nanograms per deciliter (ng/dL) STANDARD_DEVIATION 0.14 |
| Serum Testosterone Level (Total) | 15.67 nanograms per deciliter (ng/dL) STANDARD_DEVIATION 9.19 | 15.92 nanograms per deciliter (ng/dL) STANDARD_DEVIATION 10.37 | 13.02 nanograms per deciliter (ng/dL) STANDARD_DEVIATION 5.85 | 17.24 nanograms per deciliter (ng/dL) STANDARD_DEVIATION 12.5 |
| Sex: Female, Male Female | 55 Participants | 129 Participants | 20 Participants | 54 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Short Physical Performance Battery (SPPB) | 6.95 units on a scale STANDARD_DEVIATION 2.16 | 6.58 units on a scale STANDARD_DEVIATION 2.25 | 5.45 units on a scale STANDARD_DEVIATION 2.14 | 6.63 units on a scale STANDARD_DEVIATION 2.27 |
| Site Hebrew SeniorLife (HSL)/Beth Israel (BI)/Harvard Medical School | 17 Participants | 38 Participants | 5 Participants | 16 Participants |
| Site University of Colorado - Denver (UCD) | 1 Participants | 3 Participants | 2 Participants | 0 Participants |
| Site University of Connecticut (UConn Health) | 11 Participants | 26 Participants | 4 Participants | 11 Participants |
| Site University of Maryland Baltimore/Johns Hopkins University (UM/JH) | 1 Participants | 3 Participants | 2 Participants | 0 Participants |
| Site University of Pittsburgh (Pitt)/University of Pittsburgh Medical Center (UPMC) | 3 Participants | 8 Participants | 1 Participants | 4 Participants |
| Site University of Texas Medical Branch at Galveston (UTMB) | 8 Participants | 16 Participants | 1 Participants | 7 Participants |
| Site University of Utah Health (UofU) | 5 Participants | 9 Participants | 0 Participants | 4 Participants |
| Site Washington University in St. Louis (WashU) | 9 Participants | 26 Participants | 5 Participants | 12 Participants |
| Six Minute Walk Distance | 267.77 meters STANDARD_DEVIATION 86.6 | 240.73 meters STANDARD_DEVIATION 92.82 | 206.37 meters STANDARD_DEVIATION 76.82 | 225.92 meters STANDARD_DEVIATION 98.09 |
| Time from hip surgery to baseline start date | 98.29 days STANDARD_DEVIATION 32.52 | 101.24 days STANDARD_DEVIATION 32.02 | 89.65 days STANDARD_DEVIATION 21.62 | 108.54 days STANDARD_DEVIATION 33.42 |
| Total lean body mass | 36649.42 Grams STANDARD_DEVIATION 5892.42 | 36874.31 Grams STANDARD_DEVIATION 5558.35 | 35144.55 Grams STANDARD_DEVIATION 4276.92 | 37744.01 Grams STANDARD_DEVIATION 5543.42 |
| Type of Fracture Intertrochanteric Fracture | 23 Participants | 59 Participants | 13 Participants | 23 Participants |
| Type of Fracture Intracapsular or Femoral Neck Fracture | 25 Participants | 50 Participants | 3 Participants | 22 Participants |
| Type of Fracture Subtrochanteric Fracture | 7 Participants | 20 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 55 | 0 / 54 | 0 / 20 |
| other Total, other adverse events | 36 / 54 | 24 / 55 | 11 / 20 |
| serious Total, serious adverse events | 7 / 54 | 3 / 55 | 1 / 20 |
Outcome results
Primary
Change in Six Minute Walk Distance
Walking endurance was measured using a 6-Minute Walk Distance. Participants were asked to walk back and forth on a measured path marked clearly at both ends for turning purposes, while being told when each minute has passed, and receiving verbal encouragement every 60 seconds. Total distance was measured in meters with higher distances equating to higher walking endurance. Each individual participant distance from Baseline was subtracted from Month 6 to represent change over the length of the study. Higher positive values represent more improvement in walking distance. In addition to the primary analysis (unadjusted baseline to 6 month comparison), statistical contracts were evaluated to determine if there was significant between-group differences in the change from baseline to 3 months and additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline.
Time frame: Baseline to 6 months
Population: Randomized participants (N=122) who completed the primary outcome measure at baseline and one other follow-up time point (3 Months or 6 Months post randomization).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Exercise + Testosterone (EX + T) | Change in Six Minute Walk Distance | Baseline to 3 months with covariates | 24.72 Meters |
| Exercise + Testosterone (EX + T) | Change in Six Minute Walk Distance | Unadjusted baseline to 3 months | 24.10 Meters |
| Exercise + Testosterone (EX + T) | Change in Six Minute Walk Distance | Unadjusted baseline to 6 months | 42.69 Meters |
| Exercise + Testosterone (EX + T) | Change in Six Minute Walk Distance | Baseline to 6 month with covariates | 42.38 Meters |
| Exercise + Placebo (EX + P) | Change in Six Minute Walk Distance | Unadjusted baseline to 6 months | 40.50 Meters |
| Exercise + Placebo (EX + P) | Change in Six Minute Walk Distance | Baseline to 3 months with covariates | 30.23 Meters |
| Exercise + Placebo (EX + P) | Change in Six Minute Walk Distance | Unadjusted baseline to 3 months | 29.18 Meters |
| Exercise + Placebo (EX + P) | Change in Six Minute Walk Distance | Baseline to 6 month with covariates | 41.75 Meters |
| Enhanced Usual Care (EUC) | Change in Six Minute Walk Distance | Baseline to 3 months with covariates | 38.36 Meters |
| Enhanced Usual Care (EUC) | Change in Six Minute Walk Distance | Baseline to 6 month with covariates | 33.95 Meters |
| Enhanced Usual Care (EUC) | Change in Six Minute Walk Distance | Unadjusted baseline to 6 months | 37.65 Meters |
| Enhanced Usual Care (EUC) | Change in Six Minute Walk Distance | Unadjusted baseline to 3 months | 37.60 Meters |
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.55795% CI: [-23.96, 12.94]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.85395% CI: [-21.16, 25.54]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.76795% CI: [-28.57, 38.65]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.86895% CI: [-30.93, 36.62]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.9695% CI: [-24.26, 25.52]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.6395% CI: [-25.97, 42.82]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.65795% CI: [-26.77, 42.36]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.62795% CI: [-25.72, 15.56]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.36495% CI: [-42.86, 15.86]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.57495% CI: [-38, 21.15]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.30295% CI: [-39.64, 12.35]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.54195% CI: [-34.33, 18.06]Mixed Models Analysis
Secondary
Change in 1-repetition Maximum (1-RM) Leg Press Strength
Muscle strength measured as the maximal amount of weight that the participant was able to lift for one repetition (1-RM). The 1-RM is defined as the greatest resistance that could be overcome through a defined range of motion using proper techniques. Subjects were asked to move against progressively heavier resistance loads until a repetition failure was achieved. Each individual participant measure from Baseline was subtracted from Month 6 to represent change over the length of the study. Higher positive values represent the increased ability to lift more weight. Per the protocol: In addition to the primary analysis (unadjusted baseline to 6 month comparison), statistical contracts were evaluated to determine if there was significant between-group differences in the change from baseline to 3 months and additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline.
Time frame: Baseline to 6 months
Population: Randomized participants (N=122) who completed the primary outcome measure at baseline and one other follow-up time point (3 Months or 6 Months post randomization).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Exercise + Testosterone (EX + T) | Change in 1-repetition Maximum (1-RM) Leg Press Strength | Unadjusted baseline to 6 month | 62.62 pounds |
| Exercise + Testosterone (EX + T) | Change in 1-repetition Maximum (1-RM) Leg Press Strength | Baseline to 3 month with covariates | 39.01 pounds |
| Exercise + Testosterone (EX + T) | Change in 1-repetition Maximum (1-RM) Leg Press Strength | Baseline to 6 month with covarites | 64.26 pounds |
| Exercise + Testosterone (EX + T) | Change in 1-repetition Maximum (1-RM) Leg Press Strength | Unadjusted baseline to 3 month | 38.71 pounds |
| Exercise + Placebo (EX + P) | Change in 1-repetition Maximum (1-RM) Leg Press Strength | Unadjusted baseline to 3 month | 40.09 pounds |
| Exercise + Placebo (EX + P) | Change in 1-repetition Maximum (1-RM) Leg Press Strength | Baseline to 3 month with covariates | 39.25 pounds |
| Exercise + Placebo (EX + P) | Change in 1-repetition Maximum (1-RM) Leg Press Strength | Unadjusted baseline to 6 month | 61.91 pounds |
| Exercise + Placebo (EX + P) | Change in 1-repetition Maximum (1-RM) Leg Press Strength | Baseline to 6 month with covarites | 59.45 pounds |
| Enhanced Usual Care (EUC) | Change in 1-repetition Maximum (1-RM) Leg Press Strength | Baseline to 3 month with covariates | 24.52 pounds |
| Enhanced Usual Care (EUC) | Change in 1-repetition Maximum (1-RM) Leg Press Strength | Unadjusted baseline to 6 month | 38.18 pounds |
| Enhanced Usual Care (EUC) | Change in 1-repetition Maximum (1-RM) Leg Press Strength | Unadjusted baseline to 3 month | 23.23 pounds |
| Enhanced Usual Care (EUC) | Change in 1-repetition Maximum (1-RM) Leg Press Strength | Baseline to 6 month with covarites | 39.36 pounds |
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.94695% CI: [-19.61, 21.01]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.09495% CI: [-4.25, 53.13]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.10795% CI: [-5.19, 52.67]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.62795% CI: [-14.68, 24.3]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.07295% CI: [-2.2, 52.01]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.14995% CI: [-7.29, 47.49]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.84995% CI: [-15.71, 12.95]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.13495% CI: [-4.83, 35.78]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.10795% CI: [-3.68, 37.39]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.97395% CI: [-13.64, 13.17]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.13595% CI: [-4.56, 33.54]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.13495% CI: [-4.55, 34]Mixed Models Analysis
Secondary
Change in Appendicular Lean Body Mass
Lean body mass of the arms and legs, measured by dual x-ray absorptiometry (DXA). Baseline DXA scans were completed prior to the first administration of study drug. All scans were completed prior to exercise or 1-RM measurements if scheduled for the same day. DXA scans were reviewed for quality control, proper positioning, and artifacts centrally. Each individual participant measure from Baseline was subtracted from Month 6 to represent change over the length of the study. Higher positive values represent more gains in appendicular lean body mass. Per the protocol: In addition to the primary analysis (unadjusted baseline to 6 month comparison), additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline. DXA was not performed at 3 months.
Time frame: Baseline to 6 months
Population: Randomized participants (N=122) who completed the primary outcome measure at baseline and one other follow-up time point (3 Months or 6 Months post randomization).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Exercise + Testosterone (EX + T) | Change in Appendicular Lean Body Mass | Baseline to 6 month with covariates | 453.30 grams |
| Exercise + Testosterone (EX + T) | Change in Appendicular Lean Body Mass | Unadjusted baseline to 6 month | 446.35 grams |
| Exercise + Placebo (EX + P) | Change in Appendicular Lean Body Mass | Unadjusted baseline to 6 month | 429.19 grams |
| Exercise + Placebo (EX + P) | Change in Appendicular Lean Body Mass | Baseline to 6 month with covariates | 419.57 grams |
| Enhanced Usual Care (EUC) | Change in Appendicular Lean Body Mass | Unadjusted baseline to 6 month | -116.29 grams |
| Enhanced Usual Care (EUC) | Change in Appendicular Lean Body Mass | Baseline to 6 month with covariates | -212.45 grams |
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.93495% CI: [-391.74, 426.05]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.06895% CI: [-42.02, 1167.31]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.07995% CI: [-64.81, 1155.79]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure in the model with covariates.p-value: 0.86795% CI: [-365.4, 432.86]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure in the model with covariates.p-value: 0.0295% CI: [105.68, 1225.81]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure in the model with covariates.p-value: 0.02995% CI: [66.38, 1197.66]Mixed Models Analysis
Secondary
Change in Bone Mineral Density (BMD) of the Non-fractured Proximal Femur
Bone mineral density (BMD) measured by dual x-ray absorptiometry (DXA) of the non-fractured proximal femur in participants without hardware in the contralateral hip. Baseline DXA scans were completed prior to the first administration of study drug. All scans were completed prior to exercise or 1-RM measurements if scheduled for the same day. DXA scans were reviewed for quality control, proper positioning, and artifacts centrally. Per the protocol: In addition to the primary analysis (unadjusted baseline to 6 month comparison), additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline. DXA was not performed at 3 months.
Time frame: Baseline to 6 months
Population: Randomized participants (N=122) who completed the primary outcome measure at baseline and one other follow-up time point (3 Months or 6 Months post randomization).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Exercise + Testosterone (EX + T) | Change in Bone Mineral Density (BMD) of the Non-fractured Proximal Femur | Unadjusted baseline to 6 month | -0.008 g/cm^2 |
| Exercise + Testosterone (EX + T) | Change in Bone Mineral Density (BMD) of the Non-fractured Proximal Femur | Baseline to 6 month with covariates | -0.002 g/cm^2 |
| Exercise + Placebo (EX + P) | Change in Bone Mineral Density (BMD) of the Non-fractured Proximal Femur | Unadjusted baseline to 6 month | -0.001 g/cm^2 |
| Exercise + Placebo (EX + P) | Change in Bone Mineral Density (BMD) of the Non-fractured Proximal Femur | Baseline to 6 month with covariates | 0.001 g/cm^2 |
| Enhanced Usual Care (EUC) | Change in Bone Mineral Density (BMD) of the Non-fractured Proximal Femur | Unadjusted baseline to 6 month | -0.021 g/cm^2 |
| Enhanced Usual Care (EUC) | Change in Bone Mineral Density (BMD) of the Non-fractured Proximal Femur | Baseline to 6 month with covariates | 0.000 g/cm^2 |
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an Autoregressive AR(1) covariance structure.p-value: 0.82195% CI: [-0.073, 0.058]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an Autoregressive AR(1) covariance structure.p-value: 0.78995% CI: [-0.082, 0.108]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an Autoregressive AR(1) covariance structure.p-value: 0.67295% CI: [-0.075, 0.116]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an Autoregressive (1) covariance structure in the model with covariates.p-value: 0.70395% CI: [-0.013, 0.009]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an Autoregressive (1) covariance structure in the model with covariates.p-value: 0.80395% CI: [-0.017, 0.014]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an Autoregressive (1) covariance structure in the model with covariates.p-value: 0.99195% CI: [-0.015, 0.016]Mixed Models Analysis
Secondary
Change in Functional Status Questionnaire (FSQ) Total Score
The Functional Status Questionnaire (FSQ) is a self-reported measure asking about the amount of difficulty a participant experienced when performing daily tasks in the previous 4 weeks. There are a total of 6 subscales, but only the basic ADL and Intermediate ADL were used in the STEP-HI study for a total of 9 items. Scores range from 0 (high amount of difficulty completing tasks) to 36 (no difficulty completing tasks). Per the protocol: In addition to the primary analysis (unadjusted baseline to 6 month comparison), statistical contracts were evaluated to determine if there was significant between-group differences in the change from baseline to 3 months and additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline.
Time frame: Baseline to 6 months
Population: Randomized participants (N=122) who completed the primary outcome measure at baseline and one other follow-up time point (3 Months or 6 Months post randomization).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Exercise + Testosterone (EX + T) | Change in Functional Status Questionnaire (FSQ) Total Score | Baseline to 3 month with covariates | 1.83 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Functional Status Questionnaire (FSQ) Total Score | Unadjusted baseline to 3 month | 1.83 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Functional Status Questionnaire (FSQ) Total Score | Unadjusted baseline to 6 month | 2.04 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Functional Status Questionnaire (FSQ) Total Score | Baseline to 6 month with covariates | 2.02 units on a scale |
| Exercise + Placebo (EX + P) | Change in Functional Status Questionnaire (FSQ) Total Score | Unadjusted baseline to 3 month | 1.35 units on a scale |
| Exercise + Placebo (EX + P) | Change in Functional Status Questionnaire (FSQ) Total Score | Unadjusted baseline to 6 month | 1.55 units on a scale |
| Exercise + Placebo (EX + P) | Change in Functional Status Questionnaire (FSQ) Total Score | Baseline to 6 month with covariates | 1.56 units on a scale |
| Exercise + Placebo (EX + P) | Change in Functional Status Questionnaire (FSQ) Total Score | Baseline to 3 month with covariates | 1.35 units on a scale |
| Enhanced Usual Care (EUC) | Change in Functional Status Questionnaire (FSQ) Total Score | Baseline to 6 month with covariates | 3.06 units on a scale |
| Enhanced Usual Care (EUC) | Change in Functional Status Questionnaire (FSQ) Total Score | Unadjusted baseline to 6 month | 3.00 units on a scale |
| Enhanced Usual Care (EUC) | Change in Functional Status Questionnaire (FSQ) Total Score | Baseline to 3 month with covariates | 1.99 units on a scale |
| Enhanced Usual Care (EUC) | Change in Functional Status Questionnaire (FSQ) Total Score | Unadjusted baseline to 3 month | 1.95 units on a scale |
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Toeplitz covariance structure.p-value: 0.60295% CI: [-1.36, 2.33]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Toeplitz covariance structure.p-value: 0.45495% CI: [-3.48, 1.56]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Toeplitz covariance structure.p-value: 0.26295% CI: [-3.98, 1.09]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.63995% CI: [-1.47, 2.4]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.43895% CI: [-3.66, 1.59]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.26595% CI: [-4.14, 1.14]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Toeplitz covariance structure.p-value: 0.55595% CI: [-1.11, 2.07]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Toeplitz covariance structure.p-value: 0.91795% CI: [-2.39, 2.15]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Toeplitz covariance structure.p-value: 0.60695% CI: [-2.87, 1.68]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.54995% CI: [-1.09, 2.04]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.88795% CI: [-2.38, 2.06]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.57495% CI: [-2.87, 1.59]Mixed Models Analysis
Secondary
Change in Hip Rating Questionnaire Total Score
The Hip Rating Questionnaire (HRQ) Standardized is a 14-item scale with weighted questions regarding quality of life (pain level and ability to walk) and function (ability to use stairs, put on socks/shoes, use public transportation, bathe, shop, do housework, and get in and out of a chair/bed) related to the hip fracture event. The scale scores range from 16 to 100. Higher scores are associated with less pain, higher function, and better quality of life. Per the protocol: In addition to the primary analysis (unadjusted baseline to 6 month comparison), statistical contracts were evaluated to determine if there was significant between-group differences in the change from baseline to 3 months and additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline.
Time frame: Baseline to 6 months
Population: Randomized participants (N=122) who completed the primary outcome measure at baseline and one other follow-up time point (3 Months or 6 Months post randomization).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Exercise + Testosterone (EX + T) | Change in Hip Rating Questionnaire Total Score | Unadjusted baseline to 3 month | 6.52 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Hip Rating Questionnaire Total Score | Unadjusted baseline to 6 month | 8.51 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Hip Rating Questionnaire Total Score | Baseline to 6 month with covariates | 8.48 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Hip Rating Questionnaire Total Score | Baseline to 3 month with covariates | 6.52 units on a scale |
| Exercise + Placebo (EX + P) | Change in Hip Rating Questionnaire Total Score | Unadjusted baseline to 6 month | 7.55 units on a scale |
| Exercise + Placebo (EX + P) | Change in Hip Rating Questionnaire Total Score | Unadjusted baseline to 3 month | 5.98 units on a scale |
| Exercise + Placebo (EX + P) | Change in Hip Rating Questionnaire Total Score | Baseline to 3 month with covariates | 5.98 units on a scale |
| Exercise + Placebo (EX + P) | Change in Hip Rating Questionnaire Total Score | Baseline to 6 month with covariates | 7.61 units on a scale |
| Enhanced Usual Care (EUC) | Change in Hip Rating Questionnaire Total Score | Unadjusted baseline to 6 month | 6.01 units on a scale |
| Enhanced Usual Care (EUC) | Change in Hip Rating Questionnaire Total Score | Baseline to 3 month with covariates | 4.63 units on a scale |
| Enhanced Usual Care (EUC) | Change in Hip Rating Questionnaire Total Score | Unadjusted baseline to 3 month | 4.25 units on a scale |
| Enhanced Usual Care (EUC) | Change in Hip Rating Questionnaire Total Score | Baseline to 6 month with covariates | 6.01 units on a scale |
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Compound Symmetry covariance structure.p-value: 0.64995% CI: [-3.19, 5.11]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Compound Symmetry covariance structure.p-value: 0.38995% CI: [-3.22, 8.23]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Compound Symmetry covariance structure.p-value: 0.59895% CI: [-4.22, 7.31]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Compound Symmetry covariance structure in the model with covariates.p-value: 0.67695% CI: [-3.26, 5.02]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Compound Symmetry covariance structure in the model with covariates.p-value: 0.39495% CI: [-3.24, 8.19]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Compound Symmetry covariance structure in the model with covariates.p-value: 0.58595% CI: [-4.15, 7.35]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Compound Symmetry covariance structure.p-value: 0.79495% CI: [-3.56, 4.65]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Compound Symmetry covariance structure.p-value: 0.44995% CI: [-3.62, 8.16]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Compound Symmetry covariance structure.p-value: 0.56795% CI: [-4.2, 7.64]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Compound Symmetry covariance structure in the model with covariates.p-value: 0.79495% CI: [-3.56, 4.65]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Compound Symmetry covariance structure in the model with covariates.p-value: 0.52695% CI: [-3.97, 7.75]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Compound Symmetry covariance structure in the model with covariates.p-value: 0.65495% CI: [-4.55, 7.23]Mixed Models Analysis
Secondary
Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire
The OARS Multidimensional Functional Assessment Questionnaire Activities of Daily Living (ADL) is a standardized, valid and reliable, self-report questionnaire used to determine the effect of services on the functional status of older adults by asking respondents about their ability to perform ADLS on 2 subscales: Basic (BADL) and Instrumental (IADL). Both subscales are scored from 0 (significant impairment) to 14 (excellent functioning). The individual participant score from Baseline was subtracted from Month 6 to represent change over the length of the study. Higher positive values represent more improvement in functioning. In addition to the primary analysis (unadjusted baseline to 6 month comparison), statistical contracts were evaluated to determine if there was significant between-group differences in the change from baseline to 3 months and additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline.
Time frame: Baseline to 6 months
Population: Randomized participants (N=122) who completed the primary outcome measure at baseline and one other follow-up time point (3 Months or 6 Months post randomization).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Exercise + Testosterone (EX + T) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | IADL Unadjusted baseline to 6 month | 0.39 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | BADL Baseline to 6 month with covariates | 0.59 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | IADL Baseline to 3 month with covariates | 0.70 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | IADL Baseline to 6 month with covariates | 0.40 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | BADL Unadjusted baseline to 6 month | 0.60 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | IADL Unadjusted baseline to 3 month | 0.70 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | BADL Baseline to 3 month with covariates | 0.36 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | BADL Unadjusted baseline to 3 month | 0.36 units on a scale |
| Exercise + Placebo (EX + P) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | IADL Baseline to 3 month with covariates | 0.47 units on a scale |
| Exercise + Placebo (EX + P) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | BADL Baseline to 6 month with covariates | 0.36 units on a scale |
| Exercise + Placebo (EX + P) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | BADL Unadjusted baseline to 3 month | 0.14 units on a scale |
| Exercise + Placebo (EX + P) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | BADL Baseline to 3 month with covariates | 0.14 units on a scale |
| Exercise + Placebo (EX + P) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | IADL Unadjusted baseline to 6 month | 0.51 units on a scale |
| Exercise + Placebo (EX + P) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | IADL Baseline to 6 month with covariates | 0.51 units on a scale |
| Exercise + Placebo (EX + P) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | IADL Unadjusted baseline to 3 month | 0.47 units on a scale |
| Exercise + Placebo (EX + P) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | BADL Unadjusted baseline to 6 month | 0.35 units on a scale |
| Enhanced Usual Care (EUC) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | IADL Unadjusted baseline to 3 month | 0.47 units on a scale |
| Enhanced Usual Care (EUC) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | IADL Unadjusted baseline to 6 month | 0.81 units on a scale |
| Enhanced Usual Care (EUC) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | IADL Baseline to 3 month with covariates | 0.51 units on a scale |
| Enhanced Usual Care (EUC) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | BADL Unadjusted baseline to 3 month | 0.56 units on a scale |
| Enhanced Usual Care (EUC) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | BADL Unadjusted baseline to 6 month | 0.79 units on a scale |
| Enhanced Usual Care (EUC) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | BADL Baseline to 6 month with covariates | 0.83 units on a scale |
| Enhanced Usual Care (EUC) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | IADL Baseline to 6 month with covariates | 0.74 units on a scale |
| Enhanced Usual Care (EUC) | Change in Older Adult Resources and Services (OARS) Activities of Daily Living (ADL) Questionnaire | BADL Baseline to 3 month with covariates | 0.59 units on a scale |
Comparison: Comparison of the Basic Activities of Daily Living (BADL) subscale based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.32695% CI: [-0.25, 0.74]Mixed Models Analysis
Comparison: Comparison of the Basic Activities of Daily Living (BADL) subscale based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.58795% CI: [-0.87, 0.49]Mixed Models Analysis
Comparison: Comparison of the Basic Activities of Daily Living (BADL) subscale based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.21395% CI: [-1.12, 0.25]Mixed Models Analysis
Comparison: Comparison of the Basic Activities of Daily Living (BADL) subscale based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.4195% CI: [-0.32, 0.78]Mixed Models Analysis
Comparison: Comparison of the Basic Activities of Daily Living (BADL) subscale based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.52795% CI: [-0.99, 0.51]Mixed Models Analysis
Comparison: Comparison of the Basic Activities of Daily Living (BADL) subscale based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.21995% CI: [-1.23, 0.28]Mixed Models Analysis
Comparison: Comparison of the Basic Activities of Daily Living (BADL) subscale based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.35595% CI: [-0.25, 0.69]Mixed Models Analysis
Comparison: Comparison of the Basic Activities of Daily Living (BADL) subscale based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.55495% CI: [-0.88, 0.47]Mixed Models Analysis
Comparison: Comparison of the Basic Activities of Daily Living (BADL) subscale based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.21995% CI: [-1.1, 0.26]Mixed Models Analysis
Comparison: Comparison of the Basic Activities of Daily Living (BADL) subscale based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.34595% CI: [-0.24, 0.68]Mixed Models Analysis
Comparison: Comparison of the Basic Activities of Daily Living (BADL) subscale based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.49495% CI: [-0.88, 0.43]Mixed Models Analysis
Comparison: Comparison of the Basic Activities of Daily Living (BADL) subscale based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Toeplitz covariance structure in the model with covariates.p-value: 0.1895% CI: [-1.11, 0.21]Mixed Models Analysis
Comparison: Comparison of the Instrumental Activities of Daily Living (IADL) subscale based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.69395% CI: [-0.75, 0.5]Mixed Models Analysis
Comparison: Comparison of the Instrumental Activities of Daily Living (IADL) subscale based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.32795% CI: [-1.27, 0.43]Mixed Models Analysis
Comparison: Comparison of the Instrumental Activities of Daily Living (IADL) subscale based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.49395% CI: [-1.15, 0.56]Mixed Models Analysis
Comparison: Comparison of the Instrumental Activities of Daily Living (IADL) subscale based on contrasts between two groups at baseline to six months from mixed model ANOVA with an Autoregressive (1) covariance structure in the model with covariates.p-value: 0.69895% CI: [-0.72, 0.49]Mixed Models Analysis
Comparison: Comparison of the Instrumental Activities of Daily Living (IADL) subscale based on contrasts between two groups at baseline to six months from mixed model ANOVA with an Autoregressive (1) covariance structure in the model with covariates.p-value: 0.40495% CI: [-1.17, 0.47]Mixed Models Analysis
Comparison: Comparison of the Instrumental Activities of Daily Living (IADL) subscale based on contrasts between two groups at baseline to six months from mixed model ANOVA with an Autoregressive (1) covariance structure in the model with covariates.p-value: 0.58595% CI: [-1.06, 0.6]Mixed Models Analysis
Comparison: Comparison of the Instrumental Activities of Daily Living (IADL) subscale based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.39995% CI: [-0.31, 0.76]Mixed Models Analysis
Comparison: Comparison of the Instrumental Activities of Daily Living (IADL) subscale based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.55495% CI: [-0.53, 0.98]Mixed Models Analysis
Comparison: Comparison of the Instrumental Activities of Daily Living (IADL) subscale based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.99895% CI: [-0.76, 0.76]Mixed Models Analysis
Comparison: Comparison of the Instrumental Activities of Daily Living (IADL) subscale based on contrasts between two groups at baseline to three months from mixed model ANOVA with an Autoregressive (1) covariance structure in the model with covariates.p-value: 0.37895% CI: [-0.28, 0.73]Mixed Models Analysis
Comparison: Comparison of the Instrumental Activities of Daily Living (IADL) subscale based on contrasts between two groups at baseline to three months from mixed model ANOVA with an Autoregressive (1) covariance structure in the model with covariates.p-value: 0.60895% CI: [-0.53, 0.91]Mixed Models Analysis
Comparison: Comparison of the Instrumental Activities of Daily Living (IADL) subscale based on contrasts between two groups at baseline to three months from mixed model ANOVA with an Autoregressive (1) covariance structure in the model with covariates.p-value: 0.91595% CI: [-0.76, 0.69]Mixed Models Analysis
Secondary
Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health
Patient-Reported Outcomes Measurement Information System (PROMIS®) Global Health instrument is a 10 item self report questionnaire used to measure overall quality of life using 2 summary scores: Physical and Mental Health. Each summary score is standardized to the general population, with the average T-score for the US population being 50 and standard deviation of 10. Each individual participant T-score from Baseline was subtracted from Month 6 T-score to represent change over the length of the study. Higher scores represent larger increases in Physical and Mental Health. Per the protocol: In addition to the primary analysis (unadjusted baseline to 6 month comparison), statistical contracts were evaluated to determine if there was significant between-group differences in the change from baseline to 3 months and additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline.
Time frame: Baseline to 6 months
Population: Randomized participants (N=122) who completed the primary outcome measure at baseline and one other follow-up time point (3 Months or 6 Months post randomization).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Exercise + Testosterone (EX + T) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Mental Health - Baseline to 6 month with covariates | 1.47 T-score |
| Exercise + Testosterone (EX + T) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Physical Health - Unadjusted baseline to 3 month | 2.61 T-score |
| Exercise + Testosterone (EX + T) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Mental Health - Unadjusted baseline to 3 month | 1.59 T-score |
| Exercise + Testosterone (EX + T) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Mental Health - Baseline to 3 month with covariates | 1.59 T-score |
| Exercise + Testosterone (EX + T) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Mental Health - Unadjusted baseline to 6 month | 1.55 T-score |
| Exercise + Testosterone (EX + T) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Physical Health - Unadjusted baseline to 6 month | 1.89 T-score |
| Exercise + Testosterone (EX + T) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Physical Health - Baseline to 6 month with covariates | 1.88 T-score |
| Exercise + Testosterone (EX + T) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Physical Health - Baseline to 3 month with covariates | 2.61 T-score |
| Exercise + Placebo (EX + P) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Physical Health - Unadjusted baseline to 3 month | 1.09 T-score |
| Exercise + Placebo (EX + P) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Mental Health - Unadjusted baseline to 6 month | -0.76 T-score |
| Exercise + Placebo (EX + P) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Physical Health - Baseline to 3 month with covariates | 1.09 T-score |
| Exercise + Placebo (EX + P) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Mental Health - Unadjusted baseline to 3 month | 0.01 T-score |
| Exercise + Placebo (EX + P) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Mental Health - Baseline to 6 month with covariates | -0.69 T-score |
| Exercise + Placebo (EX + P) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Physical Health - Baseline to 6 month with covariates | 1.24 T-score |
| Exercise + Placebo (EX + P) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Mental Health - Baseline to 3 month with covariates | 0.00 T-score |
| Exercise + Placebo (EX + P) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Physical Health - Unadjusted baseline to 6 month | 1.25 T-score |
| Enhanced Usual Care (EUC) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Mental Health - Baseline to 3 month with covariates | 2.28 T-score |
| Enhanced Usual Care (EUC) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Physical Health - Baseline to 6 month with covariates | 4.03 T-score |
| Enhanced Usual Care (EUC) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Physical Health - Unadjusted baseline to 3 month | 1.17 T-score |
| Enhanced Usual Care (EUC) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Physical Health - Baseline to 3 month with covariates | 1.26 T-score |
| Enhanced Usual Care (EUC) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Mental Health - Baseline to 6 month with covariates | 1.93 T-score |
| Enhanced Usual Care (EUC) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Mental Health - Unadjusted baseline to 3 month | 2.19 T-score |
| Enhanced Usual Care (EUC) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Mental Health - Unadjusted baseline to 6 month | 1.58 T-score |
| Enhanced Usual Care (EUC) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health | Physical Health - Unadjusted baseline to 6 month | 4.07 T-score |
Comparison: Comparison of Physical Health Domain based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Heterogeneous Toeplitz covariance structure.p-value: 0.59795% CI: [-1.72, 2.98]Mixed Models Analysis
Comparison: Comparison of Physical Health Domain based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Heterogeneous Toeplitz covariance structure.p-value: 0.18495% CI: [-5.41, 1.04]Mixed Models Analysis
Comparison: Comparison of Physical Health Domain based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Heterogeneous Toeplitz covariance structure.p-value: 0.08995% CI: [-6.07, 0.44]Mixed Models Analysis
Comparison: Comparison of Physical Health Domain based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Heterogeneous Toeplitz covariance structure in the model with covariates.p-value: 0.63595% CI: [-2.01, 3.28]Mixed Models Analysis
Comparison: Comparison of Physical Health Domain based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Heterogeneous Toeplitz covariance structure in the model with covariates.p-value: 0.24295% CI: [-5.76, 1.46]Mixed Models Analysis
Comparison: Comparison of Physical Health Domain based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Heterogeneous Toeplitz covariance structure in the model with covariates.p-value: 0.13295% CI: [-6.42, 0.85]Mixed Models Analysis
Comparison: Comparison of Physical Health Domain based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Heterogeneous Toeplitz covariance structure.p-value: 0.19395% CI: [-0.77, 3.81]Mixed Models Analysis
Comparison: Comparison of Physical Health Domain based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Heterogeneous Toeplitz covariance structure.p-value: 0.3995% CI: [-1.86, 4.75]Mixed Models Analysis
Comparison: Comparison of Physical Health Domain based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Heterogeneous Toeplitz covariance structure.p-value: 0.96595% CI: [-3.39, 3.25]Mixed Models Analysis
Comparison: Comparison of Physical Health Domain based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Heterogeneous Toeplitz covariance structure in the model with covariates.p-value: 0.19595% CI: [-0.79, 3.82]Mixed Models Analysis
Comparison: Comparison of Physical Health Domain based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Heterogeneous Toeplitz covariance structure in the model with covariates.p-value: 0.41895% CI: [-1.93, 4.63]Mixed Models Analysis
Comparison: Comparison of Physical Health Domain based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Heterogeneous Toeplitz covariance structure in the model with covariates.p-value: 0.92195% CI: [-3.46, 3.13]Mixed Models Analysis
Comparison: Comparison of Mental Health Domain based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Heterogeneous AR Autoregressive (1) covariance structure.p-value: 0.07895% CI: [-0.26, 4.88]Mixed Models Analysis
Comparison: Comparison of Mental Health Domain based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Heterogeneous AR Autoregressive (1) covariance structure.p-value: 0.98295% CI: [-3.51, 3.43]Mixed Models Analysis
Comparison: Comparison of Mental Health Domain based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Heterogeneous AR Autoregressive (1) covariance structure.p-value: 0.18795% CI: [-5.85, 1.15]Mixed Models Analysis
Comparison: Comparison of Mental Health Domain based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Heterogeneous AR Autoregressive (1) covariance structure in the model with covariates.p-value: 0.0895% CI: [-0.26, 4.58]Mixed Models Analysis
Comparison: Comparison of Mental Health Domain based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Heterogeneous AR Autoregressive (1) covariance structure in the model with covariates.p-value: 0.78195% CI: [-3.76, 2.83]Mixed Models Analysis
Comparison: Comparison of Mental Health Domain based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Heterogeneous AR Autoregressive (1) covariance structure in the model with covariates.p-value: 0.12195% CI: [-5.94, 0.69]Mixed Models Analysis
Comparison: Comparison of Mental Health Domain based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Heterogeneous AR Autoregressive (1) covariance structure.p-value: 0.14895% CI: [-0.57, 3.73]Mixed Models Analysis
Comparison: Comparison of Mental Health Domain based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Heterogeneous AR Autoregressive (1) covariance structure.p-value: 0.69995% CI: [-3.64, 2.45]Mixed Models Analysis
Comparison: Comparison of Mental Health Domain based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Heterogeneous AR Autoregressive (1) covariance structure.p-value: 0.16395% CI: [-5.24, 0.89]Mixed Models Analysis
Comparison: Comparison of Mental Health Domain based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Heterogeneous AR Autoregressive (1) covariance structure in the model with covariates.p-value: 0.13795% CI: [-0.51, 3.69]Mixed Models Analysis
Comparison: Comparison of Mental Health Domain based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Heterogeneous AR Autoregressive (1) covariance structure in the model with covariates.p-value: 0.64895% CI: [-3.68, 2.29]Mixed Models Analysis
Comparison: Comparison of Mental Health Domain based on contrasts between two groups at baseline to three months from mixed model ANOVA with a Heterogeneous AR Autoregressive (1) covariance structure in the model with covariates.p-value: 0.13595% CI: [-5.29, 0.72]Mixed Models Analysis
Secondary
Change in Short Physical Performance Battery (SPPB) Score
The Short Physical Performance Battery (SPPB) is a well validated objective physical performance measure used to identify risk for disability. The SPPB consists of: chair rise, progressive Romberg balance, and 4 meter gait speed. Each task was scored (0-4) with a total range of 0-12. Participants who score 0 are unable to complete the tasks and participants with higher scores are considered to have higher functional mobility. Each individual participant score from Baseline was subtracted from Month 6 to represent change over the length of the study. Higher positive values represent more improvement in physical performance. In addition to the primary analysis (unadjusted baseline to 6 month comparison), statistical contracts were evaluated to determine if there was significant between-group differences in the change from baseline to 3 months and additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline.
Time frame: Baseline to 6 months
Population: Randomized participants (N=122) who completed the primary outcome measure at baseline and one other follow-up time point (3 Months or 6 Months post randomization).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Exercise + Testosterone (EX + T) | Change in Short Physical Performance Battery (SPPB) Score | Baseline to 6 month with covariates | 1.55 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Short Physical Performance Battery (SPPB) Score | Unadjusted baseline to 3 month | 1.02 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Short Physical Performance Battery (SPPB) Score | Unadjusted baseline to 6 month | 1.53 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Short Physical Performance Battery (SPPB) Score | Baseline to 3 month with covariates | 1.03 units on a scale |
| Exercise + Placebo (EX + P) | Change in Short Physical Performance Battery (SPPB) Score | Baseline to 3 month with covariates | 0.35 units on a scale |
| Exercise + Placebo (EX + P) | Change in Short Physical Performance Battery (SPPB) Score | Unadjusted baseline to 6 month | 0.68 units on a scale |
| Exercise + Placebo (EX + P) | Change in Short Physical Performance Battery (SPPB) Score | Baseline to 6 month with covariates | 0.73 units on a scale |
| Exercise + Placebo (EX + P) | Change in Short Physical Performance Battery (SPPB) Score | Unadjusted baseline to 3 month | 0.32 units on a scale |
| Enhanced Usual Care (EUC) | Change in Short Physical Performance Battery (SPPB) Score | Baseline to 3 month with covariates | 1.11 units on a scale |
| Enhanced Usual Care (EUC) | Change in Short Physical Performance Battery (SPPB) Score | Unadjusted baseline to 3 month | 1.11 units on a scale |
| Enhanced Usual Care (EUC) | Change in Short Physical Performance Battery (SPPB) Score | Baseline to 6 month with covariates | 1.43 units on a scale |
| Enhanced Usual Care (EUC) | Change in Short Physical Performance Battery (SPPB) Score | Unadjusted baseline to 6 month | 1.45 units on a scale |
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.00695% CI: [0.24, 1.46]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.86395% CI: [-0.81, 0.97]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.09195% CI: [-1.67, 0.12]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an Autoregressive (1) covariance structure in the model with covariates.p-value: 0.00995% CI: [0.21, 1.44]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an Autoregressive (1) covariance structure in the model with covariates.p-value: 0.77895% CI: [-0.76, 1.02]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an Autoregressive (1) covariance structure in the model with covariates.p-value: 0.12495% CI: [-1.59, 0.19]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.02795% CI: [0.08, 1.31]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.83395% CI: [-0.97, 0.78]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.0895% CI: [-1.67, 0.1]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an Autoregressive (1) covariance structure in the model with covariates.p-value: 0.01495% CI: [0.14, 1.21]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an Autoregressive (1) covariance structure in the model with covariates.p-value: 0.83495% CI: [-0.84, 0.68]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an Autoregressive (1) covariance structure in the model with covariates.p-value: 0.05495% CI: [-1.52, 0.01]Mixed Models Analysis
Secondary
Change in Total Lean Body Mass
Total lean body mass measured by dual x-ray absorptiometry (DXA). Baseline DXA scans were completed prior to the first administration of study drug. All scans were completed prior to exercise or 1-RM measurements if scheduled for the same day. DXA scans were reviewed for quality control, proper positioning, and artifacts centrally. Each individual participant measure from Baseline was subtracted from Month 6 to represent change over the length of the study. Higher positive values represent more gains in total lean body mass. Per the protocol: In addition to the primary analysis (unadjusted baseline to 6 month comparison), additional analysis of covariance were performed to adjust for baseline values and covariates that differed across groups at baseline. DXA was not performed at 3 months.
Time frame: Baseline to 6 months
Population: Randomized participants (N=122) who completed the primary outcome measure at baseline and one other follow-up time point (3 Months or 6 Months post randomization).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Exercise + Testosterone (EX + T) | Change in Total Lean Body Mass | Unadjusted baseline to 6 month | 922.91 grams |
| Exercise + Testosterone (EX + T) | Change in Total Lean Body Mass | Baseline to 6 month with covariates | 930.80 grams |
| Exercise + Placebo (EX + P) | Change in Total Lean Body Mass | Unadjusted baseline to 6 month | 565.19 grams |
| Exercise + Placebo (EX + P) | Change in Total Lean Body Mass | Baseline to 6 month with covariates | 547.43 grams |
| Enhanced Usual Care (EUC) | Change in Total Lean Body Mass | Unadjusted baseline to 6 month | -14.02 grams |
| Enhanced Usual Care (EUC) | Change in Total Lean Body Mass | Baseline to 6 month with covariates | 94.16 grams |
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.33695% CI: [-375.75, 1091.19]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.0995% CI: [-147.56, 2021.42]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.29795% CI: [-515.36, 1673.78]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Heterogeneous Toeplitz covariance structure in the model with covariates.p-value: 0.24595% CI: [-266.06, 1032.79]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Heterogeneous Toeplitz covariance structure in the model with covariates.p-value: 0.06995% CI: [-67.04, 1740.32]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with a Heterogeneous Toeplitz covariance structure in the model with covariates.p-value: 0.32795% CI: [-459.13, 1365.68]Mixed Models Analysis
Secondary
Change in Total Modified Physical Performance Test (mPPT) Score
A modified version of the Physical Performance Test (mPPT) was used to measure physical function. Participants were asked to complete 9 standardized tasks (book lift, putting on a lab coat, picking up a penny from the floor, standing balance, standing up five times from a 16-inch chair, 50 foot walk including a turn, 360 degree turn, stair climb for 10 steps, and climbing 2 additional flights of steps) for a total score ranging from 0 (significant impairment) to 36 (excellent functioning). Each individual participant score from Baseline was subtracted from Month 6 to represent change over the length of the study. Higher positive values represent more improvement in physical functioning.
Time frame: Baseline to 6 months
Population: Randomized participants (N=122) who completed the primary outcome measure at baseline and one other follow-up time point (3 Months or 6 Months post randomization).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Exercise + Testosterone (EX + T) | Change in Total Modified Physical Performance Test (mPPT) Score | Unadjusted baseline to 3 month | 2.60 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Total Modified Physical Performance Test (mPPT) Score | Baseline to 3 month with covariates | 2.61 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Total Modified Physical Performance Test (mPPT) Score | baseline to 6 month with covariates | 3.33 units on a scale |
| Exercise + Testosterone (EX + T) | Change in Total Modified Physical Performance Test (mPPT) Score | Unadjusted baseline to 6 month | 3.32 units on a scale |
| Exercise + Placebo (EX + P) | Change in Total Modified Physical Performance Test (mPPT) Score | Baseline to 3 month with covariates | 1.15 units on a scale |
| Exercise + Placebo (EX + P) | Change in Total Modified Physical Performance Test (mPPT) Score | baseline to 6 month with covariates | 2.20 units on a scale |
| Exercise + Placebo (EX + P) | Change in Total Modified Physical Performance Test (mPPT) Score | Unadjusted baseline to 6 month | 2.12 units on a scale |
| Exercise + Placebo (EX + P) | Change in Total Modified Physical Performance Test (mPPT) Score | Unadjusted baseline to 3 month | 1.12 units on a scale |
| Enhanced Usual Care (EUC) | Change in Total Modified Physical Performance Test (mPPT) Score | Unadjusted baseline to 6 month | 2.97 units on a scale |
| Enhanced Usual Care (EUC) | Change in Total Modified Physical Performance Test (mPPT) Score | Baseline to 3 month with covariates | 2.31 units on a scale |
| Enhanced Usual Care (EUC) | Change in Total Modified Physical Performance Test (mPPT) Score | baseline to 6 month with covariates | 2.74 units on a scale |
| Enhanced Usual Care (EUC) | Change in Total Modified Physical Performance Test (mPPT) Score | Unadjusted baseline to 3 month | 2.26 units on a scale |
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.12595% CI: [-0.34, 2.76]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.75895% CI: [-1.9, 2.61]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.45595% CI: [-3.12, 1.41]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure in the model with covariates.p-value: 0.22995% CI: [-0.72, 3]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure in the model with covariates.p-value: 0.64795% CI: [-1.97, 3.16]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to six months from mixed model ANOVA with an unstructured covariance structure in the model with covariates.p-value: 0.6895% CI: [-3.12, 2.04]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.05295% CI: [-0.02, 2.97]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.75495% CI: [-1.79, 2.46]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure.p-value: 0.29495% CI: [-3.28, 1]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure in the model with covariates.p-value: 0.03195% CI: [0.13, 2.78]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure in the model with covariates.p-value: 0.75295% CI: [-1.56, 2.16]Mixed Models Analysis
Comparison: Comparison based on contrasts between two groups at baseline to three months from mixed model ANOVA with an unstructured covariance structure in the model with covariates.p-value: 0.22395% CI: [-3.03, 0.71]Mixed Models Analysis