Cycled Testosterone Replacement Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00957528
Recruitment Status : Completed
First Posted : August 12, 2009
Results First Posted : August 21, 2012
Last Update Posted : September 10, 2012
Information provided by (Responsible Party):
The University of Texas Medical Branch, Galveston

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hypogonadism Drug: Testosterone Drug: Placebo Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Effects of Cyclic Testosterone Administration on Muscle Function in Older Individuals
Study Start Date : January 2006
Actual Primary Completion Date : December 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Placebo Comparator: Placebo
Weekly placebo treatment for a duration of 5 months.
Drug: Placebo
Weekly IM injections of sesame oil.
Other Name: Sesame Oil
Experimental: Monthly Cycled Testosterone
A month of weekly testosterone treatment alternated by a month of weekly placebo treatment for a duration of 5 months.
Drug: Testosterone
Weekly im injections of 100 mg testosterone enanthate.
Other Name: Testosterone Enanthate
Drug: Placebo
Weekly IM injections of sesame oil.
Other Name: Sesame Oil
Experimental: Continuous Testosterone
Weekly testosterone treatment for a duration of 5 months
Drug: Testosterone
Weekly im injections of 100 mg testosterone enanthate.
Other Name: Testosterone Enanthate

Primary Outcome Measures :
  1. Changes in Basal Muscle Protein Synthesis and Breakdown as Measured by Stable Isotope Metabolic Studies at Baseline and at Five Months [ Time Frame: 5 Months ]
    The fractional synthetic rate (FSR) of mixed muscle is calculated by directly measuring the incorporation of L-[ring-13C6]-phenylalanine into protein (%/hr),, using the precursor-product model: FSR = [(EP2 − EP1)/(EM•t)]•60•100, where EP1 and EP2 are the enrichments of bound L-[ring-13C6]-phenylalanine in the first and second muscle biopsies, t is the time interval (min) between biopsies, and EM is the mean L-[ring-13C6]-phenylalanine enrichment in the muscle intracellular pool.

  2. 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 [ Time Frame: 5 months ]
    Maximum weight (pounds) lifted using Cybex weight machine in a single effort(1-RM) for upper extremities (biceps and triceps) and lower extremities quadriceps and hamstrings).

  3. Changes in Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry (DEXA) [ Time Frame: 5 months ]
    Lean body mass is expressed in grams as calculated by Hologic DEXA.

Secondary Outcome Measures :
  1. Changes in Bone Mineral Density as Measured by Dual Energy X-ray Absorptiometry (DEXA) [ Time Frame: 5 months ]
    Bone mineral density measure by measured by dual energy x-ray absorptiometry (DEXA)measured at baseline and a five months

  2. Changes in Serum Markers of Bone Turnover. [ Time Frame: 5 months ]

    Measures of bone turnover markers in serum samples at baseline and at five months.The bone turnover markers analyzed include:

    Markers associated with bone breakdown NTX (N-telopeptide) TRAP5b (tartrate-resistant acid phosphatase isoform 5b) Markers associated with bone formation Osteocalcin BAP (bone specific alkaline phosphatase) Regulators of bone formation iPTH (intact parathyroid hormone) increases in response to bone loss Calcitonin inhibits bone formation in response to elevated levels of serum calcium

  3. 9473Changes in Serum Inflammatory Biomarkers and Muscle Inflammatory Cytokines [ Time Frame: 5 months ]
    Serum inflammatory biomarkers (Interleukin B-1, 2,5,6,7,8,10,12 13, Interferon gamma, GM-CSF, and Tumor Necrosis Factor alpha)as measured by immunoassay at baseline and at five months

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Ages Eligible for Study:   60 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00957528

United States, Texas
University of Texas Medical Branch
Galveston, Texas, United States, 77555
Sponsors and Collaborators
The University of Texas Medical Branch, Galveston
Principal Investigator: Randall J Urban, M.D. University of Texas

Responsible Party: The University of Texas Medical Branch, Galveston Identifier: NCT00957528     History of Changes
Other Study ID Numbers: 01-302
GCRC 615
R01AG022023 ( U.S. NIH Grant/Contract )
First Posted: August 12, 2009    Key Record Dates
Results First Posted: August 21, 2012
Last Update Posted: September 10, 2012
Last Verified: September 2012

Keywords provided by The University of Texas Medical Branch, Galveston:
Low Normal Testosterone

Additional relevant MeSH terms:
Gonadal Disorders
Endocrine System Diseases
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents