Sarcopenia
Conditions
Keywords
muscle mass, muscle loss, Deuterated creatine (D3Cr) dilution, older adults, resistance training, physical function
Brief summary
The pilot study is to assess the feasibility of using a new method to measure muscle mass called Deuterated Creatine (D3Cr) method and thereby understand the role of muscle mass on functional outcomes in older adults.
Detailed description
Muscle loss with age is considered to be an important cause of disability in older adults. However, current tools frequently used and recommended to measure muscle mass in trials have limitations: For example, DEXA (Dual-energy X-ray absorptiometry) and BIA (Bioelectrical impedance analysis)- both widely used in clinical trials cannot distinguish muscle tissue from non-muscle elements such as subcutaneous and intramuscular fat, skin, water and connective tissue. Deuterated creatine (D3Cr) dilution is a novel promising method that provides an accurate measure of the functional contractile tissue, without including the non-contractile elements, by measuring total body creatine. Our preliminary cross-sectional results in men aged \>65 years show functional muscle mass (FMM) assessed by D3-Cr to be significantly associated with performance outcomes and long-term outcomes, while DEXA showed no associations. However, these are observational data and cannot determine a causative role of muscle per se on functional outcomes. Hence, the objective of the pilot study is to assess the feasibility of our proposed future study to evaluate the role of muscle mass on functional outcomes. Specifically, the pilot study will randomize moderate to low-functioning older adults to a resistance training program or successful aging health education program to assess recruitment yields, participant adherence, retention, training program design aspects, sample size, and the cost of the main trial. Further, the impact of these changes in FMM on short-term performance outcomes, such as strength, walking speed, SPPB, self-reported measures, and balance will be examined.
Interventions
BEHAVIORALResistance Training
The intensity, volume, tempo, and progression will be based on the Federal Physical Activity guidelines. The resistance training exercises will include mainly multi-joint exercises using selectorized machines. Each session will include upper body exercises (Chest Press, Shoulder Press, Seated Rows, Bicep curls, and Tricep Extensions) and lower body exercises (Leg Press, Leg Extension and Leg Curls, and Calf raise) that will be tailored to the participant needs.
BEHAVIORALSuccessful Aging
The successful aging will attend stretching and health lectures as a group . The topics might include, medication management, disease management (e.g. blood pressure, diabetes, arthritis, dementia, pain management, diet) and other health related matters.
Sponsors
National Institute on Aging (NIA)
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Masking description
To ensure concealment of the allocation, the randomization procedures will be performed by an investigator who are not involved in the assessments. The team assessing study outcomes will be masked to intervention assignment.
Intervention model description
The pilot study will be single-blind, parallel group, randomized controlled trial of 24 moderate to low functioning participants randomized in a 1:1 allocation ratio to a high-intensity Resistance Training group (RT) or a Successful Aging Health Education comparator group (HE) for 14 weeks.
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* men and women aged 70 or greater * at high risk for mobility disability based on lower extremity functional limitations measured by Short Physical Performance battery (SPPB) with a score ≤ 8 out of 12 * could safely participate in the resistance training intervention as determined by medical history and physical examination. * willing to give informed consent to be randomized to either the resistance training group or successful aging heath education comparison group and willing to follow the study protocol
Exclusion criteria
* Severe cardiac disease, including NYHA Class III or IV congestive heart failure, clinically significant aortic stenosis, history of cardiac arrest, use of a cardiac defibrillator, or uncontrolled angina * Myocardial infarction, major heart surgery, stroke, deep vein thrombosis, or pulmonary embolus in the past 6 months * Lung disease requiring either oral or injected steroids, or the use of supplemental oxygen * Short, portable mental status questionnaire with 3 or more errors * Severe arthritis (either osteoarthritis or rheumatoid arthritis) that severely limits mobility * Severe lower back or shoulder pain that can worsen with weight lifting exercises. * Cancer requiring treatment in the past 1 year (Melanomas excluded) * Any present or recent history of severe psychiatric illness including depression that might preclude providing informed consent, safe participation, or compliance (self-report and investigator judgement * Development of chest pain or severe shortness of breath on the 400 m self-paced walk test * Parkinson's disease or other serious neurological disorders; renal disease requiring dialysis; other illness of such severity that life expectancy is considered to be less than 12 months * Current diagnosis of schizophrenia, other psychotic disorders, or bipolar disorder * Current consumption of more than 14 alcoholic drinks per week * Uncontrolled hypertension (systolic blood pressure \> 200 mm Hg and/or diastolic blood pressure \>110 mm Hg) * Currently on testosterone, Dehydroepiandrosterone (DHEA), or anabolic steroids. * Undergoing physical therapy involving the lower extremities * Currently enrolled in another randomized trial involving a pharmaceutical or lifestyle intervention. Observational studies are permitted * Participation in progressive resistance exercise regimen ( ≥1 day/week) within the previous 6 months prior to screening. * Weight change (intentional or not) over the last 6 months of \> 5% of body or plan to lose or gain weight during the study * Any other cardiovascular, pulmonary, orthopedic, neurologic, or other conditions that in the opinion of the local clinician would preclude participation and successful completion of the protocol Temporary
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Muscle Mass | Baseline and week 16 | Change in Muscle mass measured using D3Cr |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Appendicular Lean Mass (ALM) | Baseline and week 16 | Change in ALM by dual-energy x-ray absorptiometry (DEXA) |
| Lean Body Mass (LBM) | Baseline, and Week 16 | Change in LBM assessed using DXA |
| Correlation Between Changes in Muscle Mass | Baseline and Week 15 | Correlation between longitudinal changes in D3 Cr muscle mass (MM) and DXA appendicular lean mass (ALM) |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the community using flyers, posters, and mass mailings. The eligibility criteria included men and women aged 70 years or older, who were at high risk for mobility disability based on lower extremity functional limitations measured by the Short Physical Performance Battery (SPPB) with a score of 9 or lower out of 12, and not participating in a structured exercise program, and not using strength exercises in the past 6 months.
Pre-assignment details
A total of 54 participants were assessed for eligibilty and 33 were excluded ( 23 not meeting inclusion criteria (18 SPPB out of range) and 10 withdrew pre-randomization). Twenty-one participants met eligibility criteria and were subsequently randomized into 2 groups
Participants by arm
| Arm | Count |
|---|---|
| Resistance Training Group (RT) The resistance training intervention will include a full body, resistance training performed three days per week.
The intensity, volume, tempo, and progression will be based on the Federal Physical Activity guidelines
Resistance Training: The intensity, volume, tempo, and progression will be based on the Federal Physical Activity guidelines. The resistance training exercises will include mainly multi-joint exercises using selectorized machines. Each session will include upper body exercises (Chest Press, Shoulder Press, Seated Rows, Bicep curls, and Tricep Extensions) and lower body exercises (Leg Press, Leg Extension and Leg Curls, and Calf raise) that will be tailored to the participant needs. | 10 |
| Successful Aging The comparator group will meet for stretching and health education classes every 2-5 weeks up to 7 total visits.
Successful Aging: The successful aging will attend stretching and health lectures as a group . The topics might include, medication management, disease management (e.g. blood pressure, diabetes, arthritis, dementia, pain management, diet) and other health related matters. | 11 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Resistance Training Group (RT) | Successful Aging | Total |
|---|---|---|---|
| Age, Continuous | 80.4 years STANDARD_DEVIATION 5.8 | 83.6 years STANDARD_DEVIATION 5.4 | 82 years STANDARD_DEVIATION 5.6 |
| Body Mass Index (BMI) | 30 kg/m^2. STANDARD_DEVIATION 3.3 | 30 kg/m^2. STANDARD_DEVIATION 3.3 | 30 kg/m^2. STANDARD_DEVIATION 3.3 |
| D3Cr Muscle Mass | 17.3 Kg STANDARD_DEVIATION 4.2 | 18 Kg STANDARD_DEVIATION 4.9 | 17.65 Kg STANDARD_DEVIATION 4.6 |
| DXA Appendicular Lean Mass | 16.4 kg STANDARD_DEVIATION 4.2 | 17.6 kg STANDARD_DEVIATION 4.6 | 17 kg STANDARD_DEVIATION 4.4 |
| DXA Fat Mass | 35.8 Kg STANDARD_DEVIATION 8.3 | 34.4 Kg STANDARD_DEVIATION 5.2 | 35.1 Kg STANDARD_DEVIATION 6.75 |
| DXA Lean Body Mass | 44.2 Kg STANDARD_DEVIATION 11.3 | 42.2 Kg STANDARD_DEVIATION 8.9 | 43.2 Kg STANDARD_DEVIATION 10.1 |
| Number of Partcipants who had a Stroke | 1 Participants | 0 Participants | 1 Participants |
| Number of Partcipants who had Cancer. | 1 Participants | 0 Participants | 1 Participants |
| Number of Partcipants who had Myocardial Infarction or Major Heart Surgery | 0 Participants | 0 Participants | 0 Participants |
| Number of Participants taking Medications for Diabetes | 0 Participants | 3 Participants | 3 Participants |
| Number of Participants taking Medications for High Blood Pressure | 5 Participants | 8 Participants | 13 Participants |
| Number of Participants taking Medications for High Cholesterol | 5 Participants | 3 Participants | 8 Participants |
| Number of Participants with College Education or Higher | 9 Participants | 10 Participants | 19 Participants |
| Number of participants with Lung Disease | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 9 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
| Short Physical Performance Battery Score | 6.7 units on a scale STANDARD_DEVIATION 0.8 | 6.9 units on a scale STANDARD_DEVIATION 1.6 | 6.8 units on a scale STANDARD_DEVIATION 1.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 11 |
| other Total, other adverse events | 0 / 10 | 0 / 11 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Muscle Mass
Change in Muscle mass measured using D3Cr
Time frame: Baseline and week 16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resistance Training Group (RT) | Muscle Mass | 3.47 Kg | Standard Deviation 2.01 |
| Successful Aging | Muscle Mass | 1.19 Kg | Standard Deviation 1.7 |
Comparison: Continuous variables were expressed as mean (SD) and categorical variables were as frequencies and percentages. A 2-sided independent-sample t test was used to compare group differences in change scores. Change scores were calculated as Week 16 measurements minus baseline measurements. Statistical analyses were done by a blinded statistician without knowledge of group membership.p-value: 0.0395% CI: [0.22, 4.36]ANCOVA
Secondary
Appendicular Lean Mass (ALM)
Change in ALM by dual-energy x-ray absorptiometry (DEXA)
Time frame: Baseline and week 16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resistance Training Group (RT) | Appendicular Lean Mass (ALM) | 0.81 Kg | Standard Deviation 0.68 |
| Successful Aging | Appendicular Lean Mass (ALM) | -0.23 Kg | Standard Deviation 0.7 |
p-value: 0.00995% CI: [0.31, 1.77]ANCOVA
Secondary
Correlation Between Changes in Muscle Mass
Correlation between longitudinal changes in D3 Cr muscle mass (MM) and DXA appendicular lean mass (ALM)
Time frame: Baseline and Week 15
Population: We want to analyze the correlation between DXA ALM and D3Cr muscle mass. Hence, the two groups are combined to calculate the correlation of DXA ALM compared to D3Cr muscle mass in all the participants rather than individual groups.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Resistance Training Group (RT) | Correlation Between Changes in Muscle Mass | 0.19 Pearson Correlation Coefficient |
p-value: 0.4995% CI: [-0.35, 0.64]Pearson's Correlation coefficient
Secondary
Lean Body Mass (LBM)
Change in LBM assessed using DXA
Time frame: Baseline, and Week 16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resistance Training Group (RT) | Lean Body Mass (LBM) | 1.10 Kg | Standard Deviation 1.44 |
| Successful Aging | Lean Body Mass (LBM) | -0.19 Kg | Standard Deviation 0.93 |
p-value: 0.0795% CI: [-0.1, 2.67]ANCOVA