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

NCT00957801 | Completed Phase 4 Results

• 1 other identifier: 09-070
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Sarcopenia

Keywords

Sarcopenia; Aging muscle; Androgen; Cytokines; Muscle metabolism

Outcome Measures

Primary Outcomes (40)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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)

• 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)

Study Arms (4)

Testosterone injection

ACTIVE COMPARATOR

Testosterone enanthate given as a single 100 mg Intramuscular (IM) injection

Drug: Testosterone injection

Testosterone gel

ACTIVE COMPARATOR

Testosterone topical gel (Androgel 1%) 10 mg administered daily for seven days

Drug: Testosterone gel

Testosterone injection and Medrol 6 day dose pack

ACTIVE COMPARATOR

Testosterone enanthate given as a single 100mg Intramuscular (IM) injection. Medrol 6 day dose pack was administered as directed with daily doses decreasing by 4mg per day with an additional 4mg given on day 7. Day one dose: 24mg, day two dose: 20mg, day three dose: 16mg, day four dose: 12mg, day five dose: 8mg, day six dose: 4 mg, day seven dose: 4mg.

Drug: Testosterone injection; Drug: Medrol

Medrol 6 day dose pack

ACTIVE COMPARATOR

Medrol 6 day dose pack was administered as directed with daily doses decreasing by 4mg per day with an additional 4mg given on day 7. Day one dose: 24mg, day two dose: 20mg, day three dose: 16mg, day four dose: 12mg, day five dose: 8mg, day six dose: 4 mg, day seven dose: 4mg.

Drug: Medrol

Interventions

Testosterone injection DRUG

100 mg single IM injection

Also known as: Testosterone enanthate

Testosterone injection; Testosterone injection and Medrol 6 day dose pack

Testosterone gel DRUG

Testosterone gel 10 mg. administered topically daily for seven days

Also known as: Androgel 1%

Testosterone gel

Medrol DRUG

Medrol 6 day dose pack with an additional 4mg dose on day 7

Also known as: methylprednisolone, Medrol dose pack

Medrol 6 day dose pack; Testosterone injection and Medrol 6 day dose pack

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 60-85
• Gender: Male

You may not qualify if:

• 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 .
• 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.

Sponsors & Collaborators

• The University of Texas Medical Branch, Galveston: lead

Study Sites (1)

The University of Texas Medical Branch at Galveston

Galveston, Texas, 77555-0567, United States

Location

MeSH Terms

Conditions

Sarcopenia

Interventions

Testosterone; testosterone enanthate; Methylprednisolone

Condition Hierarchy (Ancestors)

Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes

Results Point of Contact

• Title: Randall J Urban, Professor and Chair, Internal Medicine
• Organization: University of Texas Medical Branch

rurban@utmb.edu

409-772-1176

Study Officials

• Randall J Urban, M.D.

  The University of Texas Medical Branch at Galveston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2009
• First Posted: August 12, 2009
• Study Start: March 1, 2009
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: May 8, 2018
• Results First Posted: April 4, 2018

Record last verified: 2018-04

Locations

US (1)