Exercise and Testosterone Therapy in Elderly Men With Physical Frailty

Phase 3

Completed

Conditions: Hip Fracture
Physical Frailty
Elective Hip Replacement
Hypogonadism

Interventions: Drug: Transdermal Testosterone gel (1%)
Behavioral: Supervised exercise training

Brief Summary: 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: 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.

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
Transdermal Testosterone gel (1%)	Transdermal Testosterone gel (1%)	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.
Transdermal Testosterone gel (1%)	Supervised exercise training	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.
Placebo gel	Supervised exercise training	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in Isokinetic Leg Extension Torque at 0 Deg/Sec	Baseline and Six Months	Leg Extension Torque measured with Cybex dynamometer at 0 deg/sec
Change in Leg Extension Torque at 60 Deg/Sec	Baseline and Six Months	Leg Extension Torque measured with Cybex dynamometry at 60 deg/sec
Change in Total Body Fat Mass	Baseline and Six Months	Total Body Fat Mass as measured by DXA
Change in Femoral Bone Mineral Density (BMD)	Baseline and Six Months	Femoral Bone Mineral Density measured with Dual X-ray Absorptiometry (DXA)
Change in Total Modified Physical Performance (mPPT) Score	Baseline and Six Months	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.
Change in Serum Testosterone Level	Baseline and Six Months	Total Serum Testosterone Level (ng/mL)