Cycled Testosterone Replacement Study

Condition(s) targeted: Hypogonadism

Intervention: Testosterone (Drug); Placebo (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: The University of Texas Medical Branch, Galveston

Official(s) and/or principal investigator(s):
Randall J Urban, M.D., Principal Investigator, Affiliation: University of Texas

The purpose of this study is to determine whether testosterone (male hormone) therapy is effective if administered in a cyclic fashion (periodic dosing) compared to continuous dosing in men aged 60 to 85 years. Effectiveness will be determined based on improvements in body composition, muscle metabolism, muscle strength, and bone metabolism.

Official title: The Effects of Cyclic Testosterone Administration on Muscle Function in Older Individuals

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome:

Changes in Basal Muscle Protein Synthesis and Breakdown as Measured by Stable Isotope Metabolic Studies at Baseline and at Five Months

Changes in Muscle Strength as Measured by Maximal Voluntary Contraction Tests (Arm Curl) at Baseline, One Month, Two Months, Three Months, Four Months, and at Five Months

Changes in Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry (DEXA)

Secondary outcome:

Changes in Bone Mineral Density as Measured by Dual Energy X-ray Absorptiometry (DEXA)

Changes in Serum Markers of Bone Turnover.

9473Changes in Serum Inflammatory Biomarkers and Muscle Inflammatory Cytokines

Detailed description: Men and women undergo a progressive reduction in lean muscle mass (sarcopenia) with advancing age regardless of their level of physical activity. A 12-yr longitudinal study in healthy sedentary older men showed a correlation between loss of muscle cross-sectional area and muscle strength of the thigh, quadriceps, and flexor muscles. Once weakened, older individuals are prone to falls that prevent independent living and diminish the quality of life. There is a need to develop therapies to counteract losses in skeletal muscle strength with aging. Studies show that exercise and testosterone administration increase skeletal muscle mass and strength in older men. However, the increase in muscle strength by testosterone in older men has not been consistent in all studies. Androgens increase muscle mass by either increasing muscle protein synthesis or inhibiting muscle protein breakdown. This proposal will investigate the hypothesis that cyclic testosterone administration (monthly on/off cycles) will preferentially increase muscle protein synthesis and result in a consistent and greater improvement in muscle strength than continuous testosterone administration.

Minimum age: 60 Years. Maximum age: 85 Years. Gender(s): Male.

Criteria:

Inclusion Criteria:

- Availability of transportation (i. e., subjects must be able to provide their own

transportation to UTMB). Exclusion Criteria:

- Medications such as anticoagulants (Coumadin) and glucocorticoids.

- History of angina that occurs with exertion or at rest.

- History of myocardial infarction within the last 12 months.

- Failure to successfully complete an exercise stress test using the Bruce protocol.

Subjects that demonstrate ≥ 0. 1 mV horizontal or downsloping ST segment depression, a drop in systolic blood pressure of ≥ 10 mm Hg, and/or frequent or repetitive arrhythmias (defined as ≥ 10 PVC/min, or couplets) during the stress test will be excluded.

- LDL cholesterol above 200 mg/dL.

- History of prostatic cancer.

- Elevated prostate specific antigen (PSA) above 4. 0 µg/L, or severe benign prostatic

hypertrophy (BPH) by history (frequent urination, reduced stream).

- Serum total testosterone concentrations of greater than 500 ng/dL.

- Subjects who engage in high intensity, elite training on a regular basis.

- Major medical illness such as diabetes, chronic obstructive pulmonary disease, or

sleep apnea.

- Recent history of smoking tobacco.

- Hematocrit greater than 51%.

- Morbidly obese older men (BMI > 35).

- Hypertension: Blood pressure on three consecutive measurements taken at one week

intervals that has a systolic pressure ≥ 140 or a diastolic blood pressure ≥ 90. Subjects will be included if they are on two or less blood pressure medications and have a blood pressure below these criteria.

- History of hepatitis or a 3-fold elevation of liver function tests (Alk phos, ALT,

AST).

- Bone related disorders such as osteoporosis or parathyroid disease.

- DEXA scans revealing lumbar spine T-scores of less than -2. 5.

- Subjects currently taking anti-bone-resorptive agents such as bisphosphonates,

parathyroid hormone, or calcitonin.

University of Texas Medical Branch, Galveston, Texas 77555, United States

Starting date: January 2006
Last updated: September 4, 2012