Exercise and Testosterone Therapy in Elderly Men With Physical Frailty

Study Overview
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Brief Summary
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The primary aim of this study is to determine, in hypogonadal older men with physical frailty, whether exercise training combined with testosterone replacement therapy can improve skeletal muscle strength, and lean mass, to a greater degree than exercise training alone.

Detailed Description
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Decreases in physical abilities, including losses of strength, endurance, balance, and coordination are major causes of disability and loss of independence in older men. Such individuals are at high risk for injurious falls, hospitalization, and use of supportive services. Age-associated testosterone deficiency may contribute to deficits in muscle mass and strength that are common in this patient population. The primary aim of this study is to determine, in hypogonadal older men with physical frailty, whether six months of exercise training combined with testosterone replacement therapy can improve skeletal muscle mass and skeletal muscle strength, to a greater degree than six months of exercise training alone. Secondary study aims are to determine in hypogonadal older men with physical frailty, whether six months of exercise training combined with testosterone replacement therapy can improve physical function, bone mineral density, and quality of life, to a greater degree than six months of exercise training alone. Comparison: Men age 65 years and older who meet criteria for physical frailty and have a serum testosterone level below 350 ng/dl are randomly assigned to one of two groups: 1) transdermal testosterone replacement therapy + supervised exercise training for six months vs. 2) inactive placebo gel + supervised exercise training for six months.

Official Title
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Exercise and Testosterone Therapy in Elderly Men With Physical Frailty

Conditions
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Physical Frailty, Hip Fracture, Elective Hip Replacement, Hypogonadism

Intervention / Treatment
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* Drug: Transdermal Testosterone gel (1%)
* Behavioral: Supervised exercise training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male, age 65 years and older Total serum testosterone level < 350 ng/dl Total Modified Physical Performance Test Score <28 Exclusion Criteria: Inability to walk 50 feet independently Current use of estrogen, progestin, or androgen containing compound Diagnosis of dementia of severity sufficient to interfere with informed consent or compliance with the protocol, or a score of 11 or greater on the Short Blessed Test of Orientation, Memory and Concentration Visual or hearing impairments that interfere with following directions Cardiopulmonary disease (recent MI, unstable angina or CHF, etc.), neuromuscular impairments, or unstable medical condition that would contraindicate progressive resistance exercise training History of prostate cancer or hormone dependent neoplasia PSA level > 4 ng/ml Serum liver transaminase levels of greater than 2 standard deviations above normal Use of drugs for osteoporosis for less than 1 year Current participation in a vigorous exercise or weight-training program more than once per week History of sleep apnea requiring use of CPAP Uncontrolled thyroid disease Diagnosis of cancer within the past 5 years other than superficial skin cancer (squamous or basal cell) hematocrit > 50% AUA symptom score > 16. History of alcohol or substance abuse Presence of severe facial acne Active symptoms of depression with GDS score > 5 and symptoms severe enough to cause >5% weight loss in previous 3 months or interfere with research assessments

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Transdermal Testosterone gel (1%)<br>Transdermal testosterone 1% gel (Androgel) provided as 2.5 gm and/or 5 gm gel packets with dose titration and monthly dose adjustments to achieve and maintain serum total testosterone level between 500-900 mg/dL. Gel to be applied daily by participants. Participants are blinded to the contents of the gel packets. Participants in this arm also perform supervised exercise training for 6 months. | Drug: Transdermal Testosterone gel (1%)<br>* Transdermal testosterone replacement therapy with Androgel(TM). Daily application of gel at 5 mg, 7.5 gm, or 10 gm for six months. Target serum total testosterone level between 500-900 ng/dl.<br>* Other names: Androgel;Behavioral: Supervised exercise training<br>* Supervised exercise training performed on site at academic medical center exercise facility. Exercise training consisted of 2 months of flexibility, balance, treadmill walking, and physical therapy-type exercises, followed by 4 months of progressive resistance training.<br>|
| Placebo Comparator: Placebo gel<br>Inactive topical gel identical in appearance to the active medication, provided in packets identical to the packaging for the active medication. Gel to be applied daily by participants. Participants are blinded to the contents of the gel packets. Participants in this arm also perform supervised exercise training for 6 months. | Behavioral: Supervised exercise training<br>* Supervised exercise training performed on site at academic medical center exercise facility. Exercise training consisted of 2 months of flexibility, balance, treadmill walking, and physical therapy-type exercises, followed by 4 months of progressive resistance training.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Total Lean Body Mass | Total Lean Mass measured by Dual X-ray Absorptiometry (DXA) | Baseline and Six Months | 
| Change in Skeletal Muscle Strength by 1-RM | One-repetition maximum strength for leg extension | Baseline and Six Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Isokinetic Leg Extension Torque at 0 Deg/Sec | Leg Extension Torque measured with Cybex dynamometer at 0 deg/sec | Baseline and Six Months | 
| Change in Leg Extension Torque at 60 Deg/Sec | Leg Extension Torque measured with Cybex dynamometry at 60 deg/sec | Baseline and Six Months | 
| Change in Total Body Fat Mass | Total Body Fat Mass as measured by DXA | Baseline and Six Months | 
| Change in Femoral Bone Mineral Density (BMD) | Femoral Bone Mineral Density measured with Dual X-ray Absorptiometry (DXA) | Baseline and Six Months | 
| Change in Total Modified Physical Performance (mPPT) Score | The Modified Physical Performance Test (mPPT) is a direct observational test that assesses multiple dimensions of physical function (basic and complex activities of daily living [ADL]) with different levels of difficulty. The test consists of 9 performance tasks. The total score range is 0-36 (min-max), with higher scores indicating better performance. Sub-scores are assigned for each of 9 item tasks; sub-score range is 0-4 (min-max) with higher scores indicating better performance. The sub-scores are summed to compute the total score. | Baseline and Six Months | 
| Change in Serum Testosterone Level | Total Serum Testosterone Level (ng/mL) | Baseline and Six Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Testosterone Replacement Therapy, Physical Frailty, Hip Fracture