Anabolic and Inflammatory Responses to Short-Term Testosterone Administration in Older Men

Sarcopenia Clinical Trial

Official title:

Anabolic and Inflammatory Responses to Short-Term Testosterone Administration in Older Men

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00957801
• Other study ID #: 09-070
• Status: Completed
• Phase: Phase 4
• Start date: March 2009
• Est. completion date: December 2015

Study information

• Verified date: April 2018
• Source: The University of Texas Medical Branch, Galveston
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 60 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Sarcopenia

Intervention

Drug:
• Testosterone injection
100 mg single IM injection
• Testosterone gel
Testosterone gel 10 mg. administered topically daily for seven days
• Medrol
Medrol 6 day dose pack with an additional 4mg dose on day 7

Locations

Country	Name	City	State
United States	The University of Texas Medical Branch at Galveston	Galveston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The University of Texas Medical Branch, Galveston

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum Total Testosterone Measured Before Treatment on Treatment Day 1 (Baseline Study)	Testosterone was measured daily during the treatment week (treatment days 1 through 8). Serum testosterone was analyzed by UTMB clinical laboratory. Normal ranges are 72-623 ng/dL.; Baseline testosterone was drawn before testosterone administration.	treatment day 1
Primary	Serum Total Testosterone Measured on Treatment Day 2	Testosterone was measured daily during the treatment week (treatment days 1 through 8). Serum testosterone was analyzed by UTMB clinical laboratory. Normal ranges are 72-623 ng/dL.; Baseline testosterone was drawn before testosterone administration.	treatment day 2
Primary	Serum Total Testosterone Measured on Treatment Day 3	TTestosterone was measured daily during the treatment week (treatment days 1 through 8). Serum testosterone was analyzed by UTMB clinical laboratory. Normal ranges are 72-623 ng/dL.; Baseline testosterone was drawn before testosterone administration.	treatment day 3
Primary	Serum Total Testosterone Measured on Treatment Day 4	Testosterone was measured daily during the treatment week (treatment days 1 through 8). Serum testosterone was analyzed by UTMB clinical laboratory. Normal ranges are 72-623 ng/dL.; Baseline testosterone was drawn before testosterone administration.	treatment day 4
Primary	Serum Total Testosterone Measured on Treatment Day 5	TesTestosterone was measured daily during the treatment week (treatment days 1 through 8). Serum testosterone was analyzed by UTMB clinical laboratory. Normal ranges are 72-623 ng/dL.; Baseline testosterone was drawn before testosterone administration.	treatment day 5
Primary	Serum Total Testosterone Measured on Treatment Day 6	Testosterone was measured daily during the treatment week (treatment days 1 through 8). Serum testosterone was analyzed by UTMB clinical laboratory. Normal ranges are 72-623 ng/dL.; Baseline testosterone was drawn before testosterone administration.	treatment day 6
Primary	Serum Total Testosterone Measured on Treatment Day 7	Testosterone was measured daily during the treatment week (treatment days 1 through 8). Serum testosterone was analyzed by UTMB clinical laboratory. Normal ranges are 72-623 ng/dL.; Baseline testosterone was drawn before testosterone administration.	treatment day 7
Primary	Serum Total Testosterone Measured on Treatment Day 8 (Post Study)	Testosterone was measured daily during the treatment week (treatment days 1 through 8). Serum testosterone was analyzed by UTMB clinical laboratory. Normal ranges are 72-623 ng/dL.; Baseline testosterone was drawn before testosterone administration.	treatment day 8
Primary	Serum Estradiol Measured on Treatment Day 1 (Baseline Study)	Estradiol was measured during the treatment week (treatment days 1 and 8). Serum estradiol was analyzed by UTMB clinical laboratory. Normal ranges are 20-47 pg/mL.	treatment day 1
Primary	Serum Estradiol Measured on Treatment Day 8 (Post Study)	Estradiol was measured during the treatment week (treatment days 1 and 8). Serum estradiol was analyzed by UTMB clinical laboratory. Normal ranges are 20-47 pg/mL.	treatment day 8
Primary	Prostate Specific Antigen (PSA) Measured on Treatment Day 1 (Baseline Study)	Prostate Specific Antigen (PSA) was measured before and after treatment week (study treatment days 1 and 8). PSA was analyzed by UTMB clinical laboratory. Normal ranges are less than 4.0 ng/mL.	treatment day 1
Primary	Prostate Specific Antigen (PSA) Measured on Treatment Day 8 (Post Study)	Prostate Specific Antigen (PSA) was measured before and after treatment week (study treatment days 1 and 8). PSA was analyzed by UTMB clinical laboratory. Normal ranges are less than 4.0 ng/mL.	treatment day 8
Primary	Hematocrit Measured on Treatment Day 1 (Baseline Study)	Hematocrit was measured before and after treatment week (study treatment days 1 and 8). Hematocrit was analyzed by UTMB clinical laboratory. Normal ranges are 38.4% - 49.3%.	treatment day 1
Primary	Hematocrit Measured on Treatment Day 8 (Post Study)	Hematocrit was measured before and after treatment week (study treatment days 1 and 8). Hematocrit was analyzed by UTMB clinical laboratory. Normal ranges are 38.4% - 49.3%.	treatment day 8
Primary	Total Cholesterol Measured on Treatment Day 1 (Baseline Study)	Total Cholesterol was measured before and after treatment week (study treatment days 1 and 8). Total cholesterol was analyzed by UTMB clinical laboratory. Normal ranges are 120-200 mg/dL.	treatment day 1
Primary	Total Cholesterol Measured on Treatment Day 8 (Post Study)	Total Cholesterol was measured before and after treatment week (study treatment days 1 and 8). Total cholesterol was analyzed by UTMB clinical laboratory. Normal ranges are 120-200 mg/dL.	treatment day 8
Primary	Triglycerides Measured on Treatment Day 1 (Baseline Study)	Triglycerides were measured before and after treatment week (study treatment days 1 and 8). Total cholesterol was analyzed by UTMB clinical laboratory. Normal ranges are 30-170 mg/dL.	treatment day 1
Primary	Triglycerides Measured on Treatment Day 8 (Post Study)	Triglycerides were measured before and after treatment week (study treatment days 1 and 8). Total cholesterol was analyzed by UTMB clinical laboratory. Normal ranges are 30-170 mg/dL.	treatment day 8
Primary	High-Density Lipoproteins (HDL) Measured on Treatment Day 1 (Baseline Study)	High Density Lipoproteins (HDL) was measured before and after treatment week (study treatment days 1 and 8). HDL was analyzed by UTMB clinical laboratory. Normal ranges are higher than 35 mg/dL.	treatment day 1
Primary	High-Density Lipoproteins (HDL) Measured on Treatment Day 8 (Post Study)	High Density Lipoproteins (HDL) was measured before and after treatment week (study treatment days 1 and 8). HDL was analyzed by UTMB clinical laboratory. Normal ranges are higher than 35 mg/dL.	treatment day 8
Primary	Low-Density Lipoproteins (LDL) Measured on Treatment Day 1 (Baseline Study)	Low Density Lipoproteins (LDL) was measured before and after treatment week (study treatment days 1 and 8). LDL was analyzed by UTMB clinical laboratory. Normal ranges are less than 160 mg/dL.	treatment day 1
Primary	Low-Density Lipoproteins (LDL) Measured on Treatment Day 8 (Post Study)	Low Density Lipoproteins (LDL) was measured before and after treatment week (study treatment days 1 and 8). LDL was analyzed by UTMB clinical laboratory. Normal ranges are less than 160 mg/dL.	treatment day 8
Primary	Very Low-Density Lipoproteins (VLDL) Measured on Treatment Day 1 (Baseline Study)	Very Low Density Lipoproteins (VLDL) was measured before and after treatment week (study treatment days 1 and 8). VLDL was analyzed by UTMB clinical laboratory. Normal ranges are 5-60 mg/dL.	treatment day 1
Primary	Very Low-Density Lipoproteins (VLDL) Measured on Treatment Day 8 (Post Study)	Very Low Density Lipoproteins (VLDL) was measured before and after treatment week (study treatment days 1 and 8). VLDL was analyzed by UTMB clinical laboratory. Normal ranges are 5-60 mg/dL.	treatment day 8
Primary	C-Reactive Protein (CRP) Measured on Treatment Day 1 (Baseline Study)	C-Reactive Protein (CRP) was measured during the treatment week (study treatment days 1 and 8). CRP was analyzed by UTMB clinical laboratory. Normal ranges are 0.0 - 0.8 mg/dL.	treatment day 1
Primary	C-Reactive Protein (CRP) Measured on Treatment Day 8 (Post Study)	C-Reactive Protein (CRP) was measured during the treatment week (study treatment days 1 and 8). CRP was analyzed by UTMB clinical laboratory. Normal ranges are 0.0 - 0.8 mg/dL.	treatment day 8
Primary	Dehydroepiandrosterone Sulfate (DHEA-S) Measured on Treatment Day 1 (Baseline Study)	Dehydroepiandrosterone sulfate (DHEA-S) was measured before and after the treatment week on study treatment days 1 and 8. DHEA-S was analyzed by immunoassay on a Siemens Immulite 2000. Normal ranges are 28-290 ug/dL.	treatment day 1
Primary	Dehydroepiandrosterone Sulfate (DHEA-S) Measured on Treatment Day 8 (Post Study)	Dehydroepiandrosterone sulfate (DHEA-S) was measured before and after the treatment week on study treatment days 1 and 8. DHEA-S was analyzed by immunoassay on a Siemens Immulite 2000. Normal ranges are 28-290 ug/dL.	treatment day 8
Primary	Sex Hormone Binding Globulin (SHBG) Measured on Treatment Day 1 (Baseline Study)	Sex Hormone Binding Globulin (SHBG) was measured before and after the treatment week on study treatment days 1 and 8. SHBG was analyzed by immunoassay on a Siemens Immulite 2000. Normal ranges are 10-57 nmol/L.	treatment day 1
Primary	Sex Hormone Binding Globulin (SHBG) Measured on Treatment Day 8 (Post Study)	Sex Hormone Binding Globulin (SHBG) was measured before and after the treatment week on study treatment days 1 and 8. SHBG was analyzed by immunoassay on a Siemens Immulite 2000. Normal ranges are 10-57 nmol/L.	treatment day 8
Primary	Insulin Measured on Treatment Day 1 (Baseline Study)	Insulin was measured before and after the treatment week on study treatment days 1 and 8. Insulin was analyzed by immunoassay on a Siemens Immulite 2000. Normal range is less than 25 uIu/mL.	treatment day 1
Primary	Insulin Measured on Treatment Day 8 (Post Study)	Insulin was measured before and after the treatment week on study treatment days 1 and 8. Insulin was analyzed by immunoassay on a Siemens Immulite 2000. Normal range is less than 25 uIu/mL.	treatment day 8
Primary	Insulin Like Growth Factor 1 (IGF-1) Measured on Treatment Day 1 (Baseline Study)	Insulin like growth factor 1 (IGF-1) was measured before and after the treatment week on study treatment days 1 and 8. IGF-1 was analyzed by immunoassay on a Siemens Immulite 2000. Normal range is 33-220 ng/mL.	treatment day 1
Primary	Insulin Like Growth Factor 1 (IGF-1) Measured on Treatment Day 8 (Post Study)	Insulin like growth factor 1 (IGF-1) was measured before and after the treatment week on study treatment days 1 and 8. IGF-1 was analyzed by immunoassay on a Siemens Immulite 2000. Normal range is 33-220 ng/mL.	treatment day 8
Primary	Cortisol Measured on Treatment Day 1 (Baseline Study) BEFORE Exercise Protocol	Cortisol was measured before and immediately after the exercise protocol, before and after the treatment week on study treatment days 1 and 8. Serum Cortisol was analyzed by immunoassay on a Siemens Immulite 2000. Normal range is 5-25 ug/dL.	treatment day 1 - before exercise
Primary	Cortisol Measured on Treatment Day 1 (Baseline Study) AFTER Exercise Protocol	Cortisol was measured before and immediately after the exercise protocol, before and after the treatment week on study treatment days 1 and 8. Serum Cortisol was analyzed by immunoassay on a Siemens Immulite 2000. Normal range is 5-25 ug/dL.	treatment day 1 - after exercise
Primary	Cortisol Measured on Treatment Day 8 (Post Study) BEFORE Exercise Protocol	Cortisol was measured before and immediately after the exercise protocol, before and after the treatment week on study treatment days 1 and 8. Serum Cortisol was analyzed by immunoassay on a Siemens Immulite 2000. Normal range is 5-25 ug/dL.	treatment day 8 - before exercise
Primary	Cortisol Measured on Treatment Day 8 (Post Study) AFTER Exercise Protocol	Cortisol was measured before and immediately after the exercise protocol, before and after the treatment week on study treatment days 1 and 8. Serum Cortisol was analyzed by immunoassay on a Siemens Immulite 2000. Normal range is 5-25 ug/dL.	treatment day 8 - after exercise
Primary	Global Fatigue Score as Measured by Brief Fatigue Inventory (BFI) in the Pre-treatment Week	The Brief Fatigue Inventory is a 9 item questionnaire that assesses perceptual fatigue as well as fatigue interferences (e.g. interference with enjoyment of life), with "0" being no fatigue and "10" being as bad as you can imagine. The Global Fatigue score is calculated by averaging the answers of all the questions.; This data is presented as the pre-treatment week average of study days -7 to -1.	Study days -7 to -1 (Pre - treatment)
Primary	Global Fatigue Score as Measured by Brief Fatigue Inventory (BFI) During the Treatment Week	The Brief Fatigue Inventory is a 9 item questionnaire that assesses perceptual fatigue as well as fatigue interferences (e.g. interference with enjoyment of life), with "0" being no fatigue and "10" being as bad as you can imagine. The Global Fatigue score is calculated by averaging the answers of all the questions.; This data is presented as the treatment week average of study days 1-8.	Study days 1-7 (treatment week)