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Cycled Testosterone Replacement Study

Primary Purpose

Hypogonadism

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Testosterone

Placebo

About this trial

This is an interventional prevention trial for Hypogonadism focused on measuring Low Normal Testosterone, Male, Aging

Eligibility Criteria

60 Years - 85 Years (Adult, Older Adult)MaleAccepts Healthy Volunteers

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.

Sites / Locations

University of Texas Medical Branch

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Monthly Cycled Testosterone

Continuous Testosterone

Arm Description

Weekly placebo treatment for a duration of 5 months.

A month of weekly testosterone treatment alternated by a month of weekly placebo treatment for a duration of 5 months.

Weekly testosterone treatment for a duration of 5 months

Outcomes

Primary Outcome Measures

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

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

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).

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

Lean body mass is expressed in grams as calculated by Hologic DEXA.

Secondary Outcome Measures

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

Bone mineral density measure by measured by dual energy x-ray absorptiometry (DEXA)measured at baseline and a five months

Changes in Serum Markers of Bone Turnover.

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

9473Changes in Serum Inflammatory Biomarkers and Muscle Inflammatory Cytokines

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

Full Information

NCT ID

NCT00957528

First Posted

August 10, 2009

Last Updated

September 4, 2012

Sponsor

The University of Texas Medical Branch, Galveston

1. Study Identification

Unique Protocol Identification Number

NCT00957528

Brief Title

Cycled Testosterone Replacement Study

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2012

Overall Recruitment Status

Completed

Study Start Date

January 2006 (undefined)

Primary Completion Date

December 2008 (Actual)

Study Completion Date

December 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The University of Texas Medical Branch, Galveston

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypogonadism

Keywords

Low Normal Testosterone, Male, Aging

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Weekly placebo treatment for a duration of 5 months.

Arm Title

Monthly Cycled Testosterone

Arm Type

Experimental

Arm Description

A month of weekly testosterone treatment alternated by a month of weekly placebo treatment for a duration of 5 months.

Arm Title

Continuous Testosterone

Arm Type

Experimental

Arm Description

Weekly testosterone treatment for a duration of 5 months

Intervention Type

Drug

Intervention Name(s)

Testosterone

Other Intervention Name(s)

Testosterone Enanthate

Intervention Description

Weekly im injections of 100 mg testosterone enanthate.

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Sesame Oil

Intervention Description

Weekly IM injections of sesame oil.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

5 Months

Title

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

Description

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).

Time Frame

5 months

Title

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

Description

Lean body mass is expressed in grams as calculated by Hologic DEXA.

Time Frame

5 months

Secondary Outcome Measure Information:

Title

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

Description

Bone mineral density measure by measured by dual energy x-ray absorptiometry (DEXA)measured at baseline and a five months

Time Frame

5 months

Title

Changes in Serum Markers of Bone Turnover.

Description

Time Frame

5 months

Title

9473Changes in Serum Inflammatory Biomarkers and Muscle Inflammatory Cytokines

Description

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

Time Frame

5 months

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

60 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Randall J Urban, M.D.

Organizational Affiliation

University of Texas

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Texas Medical Branch

City

Galveston

State/Province

Texas

ZIP/Postal Code

77555

Country

United States

12. IPD Sharing Statement

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Cycled Testosterone Replacement Study

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