Testosterone Replacement Therapy in Advanced Chronic Kidney Disease

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.

Study Overview

• Status: Completed
• Conditions: Kidney Diseases; Kidney Failure
• Intervention / Treatment: Drug: Testim, 1% testosterone gel

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 Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • VA Palo Alto Health Care System
    • San Jose, California, United States, 95128
      • Santa Clara Valley Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chronic kidney disease; Patients with chronic kidney disease between the ages of 55 and 75 years.	Drug: Testim, 1% testosterone gel; Subjects apply contents of gel packet (Testim, 1% testosterone gel) to skin daily.
No Intervention: Control; Control participants with baseline data collection only (for baseline comparator).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thigh Cross Sectional Area	DEXA-determined thigh cross-sectional area	Baseline
Lean Body Mass	DEXA-determined lean body mass	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fat Mass	DEXA-determined total body fat mass	Baseline
Quadriceps Strength	Lower body strength (in lbs) using quadriceps leg extension.	Baseline
Kidney Disease-Specific Quality of Life	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.	Baseline
Inflammatory Markers	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.	pre treatment and monthly until end of treatment
Muscle Atrophy Signaling Pathways	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.	Baseline

Collaborators and Investigators

• Sponsor: Palo Alto Veterans Institute for Research
• Investigators: Principal Investigator: Ralph Rabkin, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2007
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: March 25, 2008
• First Submitted That Met QC Criteria: March 27, 2008
• First Posted (Estimated): March 28, 2008

Study Record Updates

• Last Update Posted (Actual): August 26, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Testosterone
• Other Study ID Numbers: RAB0015AGG/SGG; IRB# 10132