TOM: Testosterone in Older Men With Sarcopenia

Study Overview
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Brief Summary
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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
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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.

Official Title
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Testosterone Replacement for Older Men With Sarcopenia

Conditions
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Sarcopenia, Hypogonadism, Muscular Diseases

Intervention / Treatment
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* Drug: Topical testosterone gel 1% (active formulation)
* Drug: Topical gel (placebo formulation)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br> | Drug: Topical testosterone gel 1% (active formulation)<br>* 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.<br>* Other names: Testim®;|
| Placebo Comparator: Placebo<br> | Drug: Topical gel (placebo formulation)<br>* Starting dose 15 g/day (3 tubes), applied to upper arms and shoulders each day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Physical Performance Measured by an Exercise Testing Regimen | Primary outcome was a change from baseline in leg-press strength at 6 months. | baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chest-Press | Change from baseline in chest press strength at 6 months | baseline and 6 months | 
| Stair-climbing Test (Without a Load) | Change from baseline in the stair-climbing test (without a load) at 6 months. | baseline and 6 month | 
| Grip Strength | Change from baseline in grip strength in the dominant hand. | baseline and 6 months | 
| 50-Meter Walking Speed (Without a Load) | Change from baseline 50-Meter Walking Speed (without a load) at 6 months | baseline and 6 months | 
| Stair-climbing Test (Loaded) | Change from baseline in Stair-climbing Test (loaded) | baseline and 6 months | 
| Late Life Functional Disability Index (LLFDI) | Percent change from baseline in the late life functional disability index at 6 months | baseline and 6 months | 
| Total Lean Mass |  | baseline, 3 months, and 6 months | 
| Total Fat Mass |  | baseline, 3 months, and 6 months | 
| 50-Meter Walking Speed (With a Load) | Change from baseline 50-Meter Walking Speed (with a load) at 6 months | baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Andropause, frailty, hormone replacement therapy, Aging