Clinical trial NCT00957801: Anabolic and Inflammatory Responses to Short-Term Testosterone Administration in Older Men
Official title: Anabolic and Inflammatory Responses to Short-Term Testosterone Administration in Older Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sarcopenia
Keywords: Sarcopenia
Aging muscle
Androgen
Cytokines
Muscle metabolism
Lead sponsor: The University of Texas Medical Branch, Galveston
Sponsor class: OTHER
First posted: 2009-08-12
Enrollment: 29
Sex: MALE
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Skeletal muscle loss is a common consequence of aging and in some individuals reaches a level that compromises health and quality of life. Age-associated increases in cytokine and inflammatory signaling may be important contributors to this process.

The investigators will assess the practical question of whether testosterone injection and gel application elicit similar responses. Resistance exercise will be used as a means of stimulating both inflammatory and anabolic responses in skeletal muscle. In order to assess the effects of testosterone on these responses, subjects will perform resistance exercise on two occasions separated by 7 days. The first session will be performed prior to the initiation of testosterone and/or medrol therapy and the second session will be performed after receiving therapy for 7 days.

Detailed description: 4 groups of healthy men aged 60 - 85 years were studied over 15 days, in 2 distinct time periods, pre-treatment and treatment.

Pre treatment week from study day -7 to study day -1. Treatment week from study day 1 to study day 8.

Groups:

1. Testosterone by injection (100mg testosterone enanthate) administered on study day 1.
2. Testosterone by gel application (10g/day Androgel 1%) administered daily beginning on study day 1 through study day 7.
3. Methylpredisone (Medrol) dose pack beginning on study day 1 (24mg) and decreasing by 4mg each day, with an additional 4mg taken on study day 7. Study day 1 (24mg), study day 2 (20mg), study day 3 (16mg), study day 4 (12mg), study day 5 (8mg), study day 6 (4mg), study day 7 (4mg).
4. Testosterone by injection (100mg testosterone enanthate) administered on study day 1 and Methylpredisone (Medrol) dose pack beginning on study day 1 (24mg) and decreasing by 4mg each day, with an additional 4mg taken on study day 7. Study day 1 (24mg), study day 2 (20mg), study day 3 (16mg), study day 4 (12mg), study day 5 (8mg), study day 6 (4mg), study day 7 (4mg).

Subjects were asked to fill out the Brief Fatigue Inventory daily for all 15 days.

Subjects were studied at the clinical research center before treatment (study day 1) and after treatment (study day 8). Resistance exercise was performed on study days 1 and 8. Blood was drawn before and after exercise for measurement of serum cortisol. Subjects were asked to return to the clinical research center each day during the treatment week (study days 1-8) for blood draws for measurement of total testosterone, estradiol and C-reactive protein (CRP). Labs were drawn on study days 1 and 8 for complete blood count, comprehensive metabolic panel and lipid panel.

Part 1:

In this part of the project we will study the acute response to testosterone treatment between two groups of subjects, comparing two methods of administration (injection vs. topical gel) in order to obtain pilot information for a subsequent, randomized, blinded long-term investigation.

Part 2:

In this part of the project we will study the acute response to Medrol (methylprednisolone) taken over 7 days with or without testosterone (given as 100mg IM) in order to obtain pilot information for a subsequent, randomized, blinded long-term investigation.

Eligibility criteria: Inclusion Criteria:

* Age: 60-85
* Gender: Male

Exclusion Criteria:

* Exclusionary medications will be an anticoagulant (Coumadin) because of the risk of bleeding during the biopsy procedure. Additional medications which will be disallowed for participation include: anabolic steroids, nitrates, antihistamines, and glucocorticoids.
* The subjects must be able to successfully complete an exercise stress test using the Bruce protocol . Subjects will be excluded without exercise testing, with a history of angina that occurs with exertion or at rest, or a myocardial infarction within the last 12 months. Subjects that demonstrate ³0.1 milliVolts (mV) horizontal or downsloping ST segment depression, a drop in systolic blood pressure of ³10 mm Hg, and/or frequent or repetitive arrhythmias (defined as ³10 premature ventricular contractions (PVC)/min, or couplets) during the stress test will be excluded.
* Subjects with LDL cholesterol above 200 mg/dL will be excluded .
* Any man with a history of breast cancer or prostate cancer, or any indication of an occult carcinoma from an elevation of prostate specific antigen (PSA) above 4.0 mg/L (53), or severe benign prostatic hypertrophy (BPH) by history (frequent urination, reduced stream) will be excluded.
* Subjects with liver dysfunction evidenced by a history of hepatitis B or hepatitis C, or by a three-fold elevation of liver enzymes (Alk phos, alanine aminotransferase (ALT), aspartate amino-transferase (AST) above normal on screening will be excluded from the study.
* Any subject with a blood pressure on three consecutive measurements taken at one week intervals that has a systolic pressure ³ 140 or a diastolic blood pressure ³ 90 will be excluded.
* Any subject who has a major medical illness such as diabetes, chronic obstructive pulmonary disease, or sleep apnea will be excluded. Moreover, subjects will not have a recent history of smoking tobacco. Morbidly obese older men (BMI \> 35) will also be excluded.
* Subjects will evidence of kidney disease (serum creatinine \> 2.0mg/dl) will be excluded from participation.
* Any subject with thyroid disease as determined by an abnormal thyroid stimulating hormone (TSH) level will be excluded from participation.
* Any subject testing positive for HIV will be excluded .
* Allergy to iodine, a component of Betadine which is used to prepare the subject's skin for invasive procedures, will be cause for exclusion from this study.
* Men with serum total testosterone concentrations greater than 500 ng/dL will be excluded.
* Subjects who engage in high intensity resistance training on a regular basis will be excluded.
* Subjects with a known coagulation disorder or with clinical evidence indicative of a bleeding disorder (easy bruising, "free bleeders") will not be enrolled in this study due to potential problems that could arise from muscle biopsy procedures.

Primary outcomes:
measure: Serum Total Testosterone Measured Before Treatment on Treatment Day 1 (Baseline Study)
timeFrame: treatment day 1
measure: Serum Total Testosterone Measured on Treatment Day 2
timeFrame: treatment day 2
measure: Serum Total Testosterone Measured on Treatment Day 3
timeFrame: treatment day 3
measure: Serum Total Testosterone Measured on Treatment Day 4
timeFrame: treatment day 4
measure: Serum Total Testosterone Measured on Treatment Day 5
timeFrame: treatment day 5
measure: Serum Total Testosterone Measured on Treatment Day 6
timeFrame: treatment day 6
measure: Serum Total Testosterone Measured on Treatment Day 7
timeFrame: treatment day 7
measure: Serum Total Testosterone Measured on Treatment Day 8 (Post Study)
timeFrame: treatment day 8
measure: Serum Estradiol Measured on Treatment Day 1 (Baseline Study)
timeFrame: treatment day 1
measure: Serum Estradiol Measured on Treatment Day 8 (Post Study)
timeFrame: treatment day 8
measure: Prostate Specific Antigen (PSA) Measured on Treatment Day 1 (Baseline Study)
timeFrame: treatment day 1
measure: Prostate Specific Antigen (PSA) Measured on Treatment Day 8 (Post Study)
timeFrame: treatment day 8
measure: Hematocrit Measured on Treatment Day 1 (Baseline Study)
timeFrame: treatment day 1
measure: Hematocrit Measured on Treatment Day 8 (Post Study)
timeFrame: treatment day 8
measure: Total Cholesterol Measured on Treatment Day 1 (Baseline Study)
timeFrame: treatment day 1
measure: Total Cholesterol Measured on Treatment Day 8 (Post Study)
timeFrame: treatment day 8
measure: Triglycerides Measured on Treatment Day 1 (Baseline Study)
timeFrame: treatment day 1
measure: Triglycerides Measured on Treatment Day 8 (Post Study)
timeFrame: treatment day 8
measure: High-Density Lipoproteins (HDL) Measured on Treatment Day 1 (Baseline Study)
timeFrame: treatment day 1
measure: High-Density Lipoproteins (HDL) Measured on Treatment Day 8 (Post Study)
timeFrame: treatment day 8
measure: Low-Density Lipoproteins (LDL) Measured on Treatment Day 1 (Baseline Study)
timeFrame: treatment day 1
measure: Low-Density Lipoproteins (LDL) Measured on Treatment Day 8 (Post Study)
timeFrame: treatment day 8
measure: Very Low-Density Lipoproteins (VLDL) Measured on Treatment Day 1 (Baseline Study)
timeFrame: treatment day 1
measure: Very Low-Density Lipoproteins (VLDL) Measured on Treatment Day 8 (Post Study)
timeFrame: treatment day 8
measure: C-Reactive Protein (CRP) Measured on Treatment Day 1 (Baseline Study)
timeFrame: treatment day 1
measure: C-Reactive Protein (CRP) Measured on Treatment Day 8 (Post Study)
timeFrame: treatment day 8
measure: Dehydroepiandrosterone Sulfate (DHEA-S) Measured on Treatment Day 1 (Baseline Study)
timeFrame: treatment day 1
measure: Dehydroepiandrosterone Sulfate (DHEA-S) Measured on Treatment Day 8 (Post Study)
timeFrame: treatment day 8
measure: Sex Hormone Binding Globulin (SHBG) Measured on Treatment Day 1 (Baseline Study)
timeFrame: treatment day 1
measure: Sex Hormone Binding Globulin (SHBG) Measured on Treatment Day 8 (Post Study)
timeFrame: treatment day 8
measure: Insulin Measured on Treatment Day 1 (Baseline Study)
timeFrame: treatment day 1
measure: Insulin Measured on Treatment Day 8 (Post Study)
timeFrame: treatment day 8
measure: Insulin Like Growth Factor 1 (IGF-1) Measured on Treatment Day 1 (Baseline Study)
timeFrame: treatment day 1
measure: Insulin Like Growth Factor 1 (IGF-1) Measured on Treatment Day 8 (Post Study)
timeFrame: treatment day 8
measure: Cortisol Measured on Treatment Day 1 (Baseline Study) BEFORE Exercise Protocol
timeFrame: treatment day 1 - before exercise
measure: Cortisol Measured on Treatment Day 1 (Baseline Study) AFTER Exercise Protocol
timeFrame: treatment day 1 - after exercise
measure: Cortisol Measured on Treatment Day 8 (Post Study) BEFORE Exercise Protocol
timeFrame: treatment day 8 - before exercise
measure: Cortisol Measured on Treatment Day 8 (Post Study) AFTER Exercise Protocol
timeFrame: treatment day 8 - after exercise
measure: Global Fatigue Score as Measured by Brief Fatigue Inventory (BFI) in the Pre-treatment Week
timeFrame: Study days -7 to -1 (Pre - treatment)
measure: Global Fatigue Score as Measured by Brief Fatigue Inventory (BFI) During the Treatment Week
timeFrame: Study days 1-7 (treatment week)
Secondary outcomes:
Other outcomes:
Locations:
city: Galveston
country: United States
facility: The University of Texas Medical Branch at Galveston
state: Texas
Study officials:
affiliation: The University of Texas Medical Branch at Galveston
name: Randall J Urban, M.D.
role: PRINCIPAL_INVESTIGATOR
References: