Hypogonadism, Muscular Diseases, Sarcopenia
Conditions
Keywords
Andropause, frailty, hormone replacement therapy, Aging
Brief summary
The purpose of this study is to determine whether testosterone replacement in older men with low testosterone levels will increase muscle strength, improve physical performance and overall sense of well being, and reduce fatigue.
Detailed description
The primary objective of this study is to determine whether testosterone replacement in older men, who have low testosterone levels and mild to moderate physical impairment, will increase their maximal voluntary muscle strength of major upper and lower extremity muscle groups. The second objective is to determine whether testosterone replacement will improve the power of knee extension, physical performance tests, the level of physical activity (measured by 3D accelerometer), self-reported disability, exercise tolerance and mobility. The third objective is to determine whether testosterone supplementation improves fatigue, affect, and overall sense of well being in older men with low testosterone levels. A fourth objective is to define the Minimum Clinically Important Differences in physical measures perceived by the participants (MCID). Participant involvement will require 15-17 clinic visits over 28 weeks. Five to 7 of these visits are for physical testing, including body composition, muscle performance, and physical function. Throughout the study, hormone measurements will be obtained.
Interventions
DRUGTopical testosterone gel 1% (active formulation)
Starting dose 10 g/day; increased to 15 g/day or decreased to 5 g/day in order to attain morning total testosterone level between 500 - 1000 ng/dL. Blinding achieved by combining a total of 3 tubes of active or placebo gel, applied to upper arms and shoulders each day.
DRUGTopical gel (placebo formulation)
Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.
Sponsors
National Institute on Aging (NIA)
Boston Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Community dwelling, ages 65 and older * Self-reported difficulty in climbing 10 steps without resting, or difficulty in walking 2 or 3 blocks outside on level ground * A score of 4 to 9 on the Short Physical Performance Battery (mild to moderate physical impairment) * Total serum testosterone level (TT) \< 350 ng/dL and \> 100 ng/dL * Without dementia (Mini-Mental State Examination \[MMSE\] score \> 24)
Exclusion criteria
* Use of testosterone, anabolic steroids, dehydroepiandrosterone (DHEA), androstenedione or recombinant growth hormone (rGH) in the past year * Alcohol or drug abuse * Use of anti-convulsants or glucocorticoids (equivalent to prednisone \> 20 mg/day) * Prostate cancer, breast cancer or other cancers with life expectancy \< 5 years * Limiting neuromuscular, joint or bone disease, or history of stroke with residual neurological problems * Any neurological condition that would impact cognitive functioning including: * epilepsy * multiple sclerosis * HIV * Parkinson's disease * stroke * other focal lesion * Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I psychiatric disorder in past year or use of psychotropic medications in 6 months * Abnormal prostate examination; PSA \> 4 ng/mL; or BPH symptom score \> 21 * Unstable angina, New York (NY) class III or IV congestive heart failure or myocardial infarction within 3 months of entry * Abnormal laboratory values (at discretion of principal investigator) * Untreated thyroid disease; systolic blood pressure \> 160 or diastolic \> 100 mm Hg * Body mass index \> 40 kg/m2 * Untreated severe obstructive sleep apnea
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Physical Performance Measured by an Exercise Testing Regimen | baseline and 6 months | Primary outcome was a change from baseline in leg-press strength at 6 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Fat Mass | baseline, 3 months, and 6 months | — |
| 50-Meter Walking Speed (With a Load) | baseline and 6 months | Change from baseline 50-Meter Walking Speed (with a load) at 6 months |
| Chest-Press | baseline and 6 months | Change from baseline in chest press strength at 6 months |
| Stair-climbing Test (Without a Load) | baseline and 6 month | Change from baseline in the stair-climbing test (without a load) at 6 months. |
| Total Lean Mass | baseline, 3 months, and 6 months | — |
| 50-Meter Walking Speed (Without a Load) | baseline and 6 months | Change from baseline 50-Meter Walking Speed (without a load) at 6 months |
| Stair-climbing Test (Loaded) | baseline and 6 months | Change from baseline in Stair-climbing Test (loaded) |
| Late Life Functional Disability Index (LLFDI) | baseline and 6 months | Percent change from baseline in the late life functional disability index at 6 months |
| Grip Strength | baseline and 6 months | Change from baseline in grip strength in the dominant hand. |
Countries
United States
Participant flow
Recruitment details
All participants provided written, informed consent. Recruitment took place at VAHCS, NERI, and BUMC. Outcome assessments were performed at BUMC. The study consisted of a 24- week intervention followed by a 12-week observation period. Enrollment took place between September 2005 and December 2009.
Pre-assignment details
The participants were community-dwelling men, aged 65 years and older, with total testosterone between 100 and 350 ng/dL or free testosterone less than 50 pg/mL, and mobility limitation.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Topical testosterone gel 1% (active formulation): Starting dose 10 g/day; increased to 15 g/day or decreased to 5 g/day in order to attain morning total testosterone level between 500 - 1000 ng/dL. Blinding achieved by combining a total of 3 tubes of active or placebo gel, applied to upper arms and shoulders each day. | 106 |
| Placebo Topical gel (placebo formulation): Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day. | 103 |
| Total | 209 |
Baseline characteristics
| Characteristic | Placebo | Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 103 Participants | 106 Participants | 209 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 74 Years STANDARD_DEVIATION 5 | 74 Years STANDARD_DEVIATION 6 | 74 Years STANDARD_DEVIATION 5.4 |
| Region of Enrollment United States | 103 participants | 106 participants | 209 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 103 Participants | 106 Participants | 209 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 106 | 10 / 103 |
| serious Total, serious adverse events | 16 / 106 | 8 / 103 |
Outcome results
Primary
Changes in Physical Performance Measured by an Exercise Testing Regimen
Primary outcome was a change from baseline in leg-press strength at 6 months.
Time frame: baseline and 6 months
Population: Participants with baseline and at least one post baseline measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment | Changes in Physical Performance Measured by an Exercise Testing Regimen | 156.9 Newtons |
| Placebo | Changes in Physical Performance Measured by an Exercise Testing Regimen | 27.1 Newtons |
p-value: 0.00395% CI: [43.9, 215.6]t-test, 2 sided
p-value: 0.00495% CI: [43.5, 215.4]Regression, Linear
Secondary
50-Meter Walking Speed (With a Load)
Change from baseline 50-Meter Walking Speed (with a load) at 6 months
Time frame: baseline and 6 months
Population: Participants with a baseline and one post baseline measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment | 50-Meter Walking Speed (With a Load) | 0.139 meters/second |
| Placebo | 50-Meter Walking Speed (With a Load) | 0.065 meters/second |
p-value: 0.2495% CI: [-0.05, 0.19]t-test, 2 sided
p-value: 0.1495% CI: [-0.03, 0.209]Regression, Linear
Secondary
50-Meter Walking Speed (Without a Load)
Change from baseline 50-Meter Walking Speed (without a load) at 6 months
Time frame: baseline and 6 months
Population: Participants with a baseline and one post baseline measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment | 50-Meter Walking Speed (Without a Load) | 0.074 meters/second |
| Placebo | 50-Meter Walking Speed (Without a Load) | 0.024 meters/second |
p-value: 0.2695% CI: [-0.035, 0.135]t-test, 2 sided
p-value: 0.2795% CI: [-0.037, 0.133]Regression, Linear
Secondary
Chest-Press
Change from baseline in chest press strength at 6 months
Time frame: baseline and 6 months
Population: Participants with baseline and 1 post baseline measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment | Chest-Press | 34.7 Newtons |
| Placebo | Chest-Press | 0.28 Newtons |
p-value: 0.00295% CI: [13.2, 55.8]t-test, 2 sided
p-value: 0.00295% CI: [13.1, 56.2]Regression, Linear
Secondary
Grip Strength
Change from baseline in grip strength in the dominant hand.
Time frame: baseline and 6 months
Population: The participants with baseline and one post baseline measure are included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment | Grip Strength | 1.0 Kilograms |
| Placebo | Grip Strength | 0.7 Kilograms |
p-value: 0.6995% CI: [-1.1, 1.7]t-test, 2 sided
p-value: 0.7195% CI: [-1.1, 1.7]Regression, Linear
Secondary
Late Life Functional Disability Index (LLFDI)
Percent change from baseline in the late life functional disability index at 6 months
Time frame: baseline and 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment | Late Life Functional Disability Index (LLFDI) | 61.2 units on a scale |
| Placebo | Late Life Functional Disability Index (LLFDI) | 61.7 units on a scale |
Secondary
Stair-climbing Test (Loaded)
Change from baseline in Stair-climbing Test (loaded)
Time frame: baseline and 6 months
Population: Participants with one baseline and one post baseline measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment | Stair-climbing Test (Loaded) | 39.2 Watts |
| Placebo | Stair-climbing Test (Loaded) | 9.0 Watts |
p-value: 0.0595% CI: [0.3, 60.1]t-test, 2 sided
p-value: 0.0595% CI: [0.2, 59.3]Regression, Linear
Secondary
Stair-climbing Test (Without a Load)
Change from baseline in the stair-climbing test (without a load) at 6 months.
Time frame: baseline and 6 month
Population: Participants with baseline and one post baseline measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment | Stair-climbing Test (Without a Load) | 19.5 Watts |
| Placebo | Stair-climbing Test (Without a Load) | 10.7 Watts |
p-value: 0.3495% CI: [-9.2, 26.7]t-test, 2 sided
p-value: 0.3795% CI: [-9.9, 26.2]Regression, Linear
Secondary
Total Fat Mass
Time frame: baseline, 3 months, and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Total Fat Mass | Baseline (N=82,81) | 26.2 Kilograms | Standard Deviation 7.5 |
| Treatment | Total Fat Mass | 3 Months (N=73,75) | 24.9 Kilograms | Standard Deviation 7.1 |
| Treatment | Total Fat Mass | 6 Months (N=77,80) | 24.0 Kilograms | Standard Deviation 6.8 |
| Placebo | Total Fat Mass | Baseline (N=82,81) | 28 Kilograms | Standard Deviation 8.4 |
| Placebo | Total Fat Mass | 3 Months (N=73,75) | 28 Kilograms | Standard Deviation 8.1 |
| Placebo | Total Fat Mass | 6 Months (N=77,80) | 27.5 Kilograms | Standard Deviation 7.9 |
p-value: 0.00295% CI: [-2.7, -0.6]t-test, 2 sided
p-value: <0.000195% CI: [-2.8, -1.2]t-test, 2 sided
Secondary
Total Lean Mass
Time frame: baseline, 3 months, and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Total Lean Mass | Baseline | 55.1 Kilograms | Standard Deviation 6.9 |
| Treatment | Total Lean Mass | 3 Months (N=73,75) | 57.2 Kilograms | Standard Deviation 7.1 |
| Treatment | Total Lean Mass | 6 Months (N=77,80) | 56.1 Kilograms | Standard Deviation 6.9 |
| Placebo | Total Lean Mass | Baseline | 56.5 Kilograms | Standard Deviation 6.5 |
| Placebo | Total Lean Mass | 3 Months (N=73,75) | 56.7 Kilograms | Standard Deviation 6.2 |
| Placebo | Total Lean Mass | 6 Months (N=77,80) | 56.2 Kilograms | Standard Deviation 6.3 |
p-value: 0.295% CI: [1.2, 2.5]t-test, 2 sided
p-value: <0.000195% CI: [0.4, 2.2]t-test, 2 sided