Testosterone Replacement Therapy in Advanced Chronic Kidney Disease

Study Overview
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Brief Summary
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Muscle wasting is common in advanced chronic kidney disease (CKD) and adversely affects morbidity and mortality. In 2/3 of males with advanced CKD serum testosterone (TT) levels are reduced, and likely contributes to the wasting. As TT in relatively safe physiologic replacement doses, increases muscle mass in otherwise normal TT deficient subjects, we hypothesize that physiologic TT replacement will be effective in preventing and treating the loss of muscle mass and function in CKD patients, will improve quality of life and may reduce some cardiovascular disease (CVD) risk factors.

Official Title
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Testosterone Replacement Therapy in Advanced Chronic Kidney Disease

Conditions
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Kidney Failure, Kidney Diseases

Intervention / Treatment
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* Drug: Testim (1% testosterone gel)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:Inclusion criteria: CKD subjects; males with calculated GFR (MRDR equation) between 15 and 40 ml/min/1.73m2 and stable or slowly progressive renal failure (decline in function of <1ml/min/month) including those patients requiring hemodialysis and serum testosterone levels of <300 ng/ml and capable of safely performing required exercise testing and serum testosterone levels of <300ng/ml and capable of safely performing required exercise testing. Control subjects; good health, normal serum creatinine levels, normal TT levels and able to perform required exercise testing safely. The racial and ethnic composition of the subjects will reflect the composition present in the ESRD population in the counties in Northern California from which our patients are referred. Subjects to be of age 45-80 years. Exclusion Criteria:Exclusion criteria: applicable to both CKD and control subjects. Any unstable chronic medical condition, previous kidney transplant. Uncontrolled diabetes mellitus, active vasculitis, active autoimmune disease, malignancy(<5 yrs), obesity (BMI > 35), alcoholism or other recreational drug use, active heart disease, angina, uncontrolled arrhythmias or myocardial infarct within past 3 months, peripheral vascular disease with claudication, active lung, liver or GI disease, sleep apnea, medically unstable subjects and subjects who received anabolic, catabolic or cytotoxic medications during the prior 3 months. History of prostate CA, PSA >4g/ml, or advanced BPH (AUA symptom score > 21) and abnormal prostate on digital rectal examination. Bone or joint abnormalities that would preclude exercise testing.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Testim (1% testosterone gel)|Subjects apply contents of gel packet to skin daily.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lean body mass |  | pre and post treatment | 
| Fat mass |  | pre and post treatment | 
| Thigh cross sectional area |  | pre and post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quadriceps strength |  | pre and post treatment | 
| Physical Function |  | pre and post treatment | 
| Quality of Life |  | pre and post treatment | 
| Inflammatory markers |  | pre treatment and monthly until end of treatment | 
| Muscle atrophy signaling pathways |  | pre and post treatment |