Testosterone Replacement Therapy in Advanced Chronic Kidney Disease

Not Applicable

Completed

• Conditions: Kidney Failure; Kidney Diseases
• Interventions: Drug: Testim, 1% testosterone gel

• Registration Number: NCT00645658
• Lead Sponsor: Palo Alto Veterans Institute for Research

Brief Summary

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.

Detailed Description

All subjects will undergo baseline testing that will consist of functional capacity tests, blood tests and muscle biopsies (described in detail below). Subjects will then receive testosterone gel which will be applied daily to the skin of the abdomen or thighs every morning at the same time for 16 weeks. Two days after the hormone treatment is started, the blood testosterone (TT) level will be measured 6 hours after administration. Our goal will be the attainment of serum total TT levels in the mid- to upper normal young adult range. If the serum TT is not at goal, the dose of gel will be increased or decreased repeat testing will be performed within one week. All subjects will be tested for serum TT levels every 4 weeks to assure that the serum total TT remains at goal level. Measurements will be repeated at 8 and 16 weeks.

Study Timeline

• Study Start: 2007-08
• Study First Submitted: 2008-03-25
• Study First Submitted QC: 2008-03-27
• Study First Posted: 2008-03-28
• Primary Completion: 2010-08
• Study Completion: 2010-08
• Results First Submitted: 2022-11-22
• Status Verified: 2024-07
• Results First Submitted QC: 2024-07-31
• Last Update Submitted: 2024-07-31
• Results First Posted: 2024-08-26
• Last Update Posted: 2024-08-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 17

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chronic kidney disease	Testim, 1% testosterone gel	Patients with chronic kidney disease between the ages of 55 and 75 years.

Primary Outcome Measures

Name	Time	Method
Thigh Cross Sectional Area	Baseline	DEXA-determined thigh cross-sectional area
Lean Body Mass	Baseline	DEXA-determined lean body mass

Secondary Outcome Measures

Name	Time	Method
Fat Mass	Baseline	DEXA-determined total body fat mass
Kidney Disease-Specific Quality of Life	Baseline	Questionnaire - SF-36, which stands for the Short Form 36 Health Survey. It is a widely used standardized 36 item quality of life assessment. This particular measure focused on symptoms, and is scaled from zero to 100, with a higher score indicating better health functioning.
Inflammatory Markers	pre treatment and monthly until end of treatment	C-Reactive Protein (CRP). CRP is measured in mg/l and is a marker of inflammation. CRP generally ranges from \<1.0 to 5 mg/L. A normal value is less than 2.0 mg/L.
Quadriceps Strength	Baseline	Lower body strength (in lbs) using quadriceps leg extension.
Muscle Atrophy Signaling Pathways	Baseline	These include muscle growth regulatory factors, IGF-1 and myostatin, their receptors and components of the ubiquitin-proteasome and calpain proteolytic pathways and inflammatory cytokines.

Trial Locations

Locations (2)

VA Palo Alto Health Care System; 🇺🇸 Palo Alto, California, United States

Santa Clara Valley Medical Center; 🇺🇸 San Jose, California, United States