Clinical trial NCT00645658: Testosterone Replacement Therapy in Advanced Chronic Kidney Disease
Official title: Testosterone Replacement Therapy in Advanced Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Kidney Failure
Kidney Diseases
Lead sponsor: Palo Alto Veterans Institute for Research
Sponsor class: OTHER
First posted: 2008-03-28
Enrollment: 17
Sex: MALE
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Thigh Cross Sectional Area
timeFrame: Baseline
measure: Lean Body Mass
timeFrame: Baseline
Secondary outcomes:
measure: Fat Mass
timeFrame: Baseline
measure: Quadriceps Strength
timeFrame: Baseline
measure: Kidney Disease-Specific Quality of Life
timeFrame: Baseline
measure: Inflammatory Markers
timeFrame: pre treatment and monthly until end of treatment
measure: Muscle Atrophy Signaling Pathways
timeFrame: Baseline
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
city: San Jose
country: United States
facility: Santa Clara Valley Medical Center
state: California
Study officials:
affiliation: Stanford University
name: Ralph Rabkin
role: PRINCIPAL_INVESTIGATOR
References: