Resistance Exercise for the Prevention of Age-related Sarcopenia

Study Overview
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Brief Summary
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The purpose of this study is to determine the benefits of negative work progressive resistance exercise (PRE) for the conservative management of sarcopenia in older male Veterans at the DC VAMC. Efficacy will be assessed by examining post-exercise changes in metabolic and inflammatory markers, muscle morphology, strength, and functional status.

Detailed Description
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The chief aim of this protocol is to determine the efficacy of negative work progressive resistance exercise (PRE) in the management of sarcopenia in older male Veterans at the DC VAMC. This proposed study is a randomized clinical trial using a single-arm, delayed cross-over design with repeated measures. This method is a patient-first approach to clinical research that permits all participants to receive the intervention while allowing the investigators to conduct both within subjects and between subjects comparisons with a modest study enrollment. During the pre-treatment period we will recruit, screen, and consent 30 older men with sarcopenia. The participants will be randomized into two groups: active treatment and delayed treatment. The initial active treatment and delayed treatment periods will last 12 weeks. After 12 weeks, the participants in the delayed treatment group will crossover (without a washout period) and start 12 weeks of intervention. All participants will detrain and be monitored for follow up during their respective 12-week post treatment period. Outcome measures include post-exercise changes in metabolic and inflammatory markers, muscle morphology, strength, and functional status.

Official Title
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Negative Work Exercise as a Novel Treatment for Sarcopenia in Older Men

Conditions
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Sarcopenia

Intervention / Treatment
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* Behavioral: Negative work exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult, ambulatory males > 60 years old (n=30) will be recruited for this proposed study. Participant inclusion criteria also includes having clinically significant sarcopenia based on the body composition assessment showing an aLM that is < 2 SD below the mean values of a young adult reference group using DEXA scanning. Exclusion Criteria: Exclusion criteria include BMI scores > 30 or a Mini-Mental Status exam score of < 22. The second tier of screening will include the following blood tests, obtained between 8-9 AM, following a 12-hour overnight fast: CBC, routine chemistry profile (e.g., glucose, kidney and liver function tests). Veterans with an elevated fasting blood glucose by WHO criteria (FBG >110 mg/dl), triglyceride levels > 200 mg/dL, and/or known DM, or abnormalities of other routine blood tests (i.e., > 2 SD beyond normal) will be excluded from the study. Uncontrolled cardiovascular disease, non-ambulatory status, evidence of a major disease exacerbation over the last six months, and current participation in a supervised exercise program (minimum of three months, twice per week) would also preclude participation in this study.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Exercise group 1: Negative work exercise | Behavioral: Negative work exercise<br>* Submaximal negative work exercise using an isokinetic dynamometer will be performed twice per week for 12 weeks. Exercise volume will be 3 sets of 10 repetitions for the knee and shoulder extensors.<br>* Other names: Biodex;|
| Other: 2<br>Exercise group 2: Negative work exercise (delayed start for single-arm crossover trial) | Behavioral: Negative work exercise<br>* Submaximal negative work exercise using an isokinetic dynamometer will be performed twice per week for 12 weeks. Exercise volume will be 3 sets of 10 repetitions for the knee and shoulder extensors.<br>* Other names: Biodex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in insulin sensitivity following the exercise intervention as estimated with the QUICKI algorithm (quantitative insulin sensitivity check index) | Blood tests will be obtained after a 12- hour overnight fast at baseline, weeks 6, week 12 and week 24: glucose and insulin values will be determined before and during a standard (75 g) 2 hour oral glucose tolerance test (to determine insulin sensitivity via QUICKI algorithm. | Change from baseline in QUICKI values at week 6, week 12, and week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak isokinetic torque | Isokinetic knee and shoulder extension torques will be obtained bilaterally using the Biodex System 3 | Treatment weeks: 1, 6, and 12; post-treatment weeks: 6 and 12 | 
| Diagnostic ultrasongraphy | Muscle thickness, pennation angle, and area at the flexor digitorum superficialis, lower-trapezius, rectus femoris and tibialis anterior (dominant side only). | Treatment weeks: 1, 6, and 12; post-treatment weeks: 6 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aging, sarcopenia, rehabilitation, exercise