Official Title: “5-Alpha Reductase and Anabolic Effects of Testosterone”

The purpose of this study is to determine whether a higher-than-replacement dose of testosterone and finasteride can be combined to safely increase muscle strength in older men who have a low blood concentration of testosterone.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Factorial Assignment, Efficacy Study

Study Primary Completion Date: June 2010

Approximately 40% of older male veterans have a low serum testosterone concentration. The latter is associated with diminished muscle strength and bone mineral density, depressed mood, low pain tolerance, frailty, and increased mortality. Replacement doses of testosterone have been administered to hypogonadal men for the purpose of reversing deficits in muscle and bone. Although testosterone is clearly important for maintaining muscle and bone in men, there are problems associated with T replacement. First, testosterone causes a number of undesired effects, including fluid retention, gynecomastia, worsening of sleep apnea, polycythemia, prostate enlargement and acceleration of early-stage prostate cancer . The anabolic effects obtained to date from testosterone replacement have been relatively modest, especially in older men . Our hypothesis is that combined treatment with a higher-than-replacement dose of testosterone and a 5- reductase inhibitor will produce substantial anabolic effects, while preventing testosterone-induced prostate enlargement and possibly other adverse effects.

We plan to investigate the efficacy and safety of combined treatment with testosterone and finasteride in older hypogonadal male veterans by conducting a 12-month randomized, placebo-controlled trial. We will administer a higher-than-replacement dose of testosterone plus the 5- reductase inhibitor finasteride to a group of hypogonadal, but otherwise healthy older men. We will determine whether this treatment is a safe and effective means to increase muscle mass and strength. Men aged 60 to 80, with circulating total testosterone 300 ng/dL or bioavailable testosterone 70 ng/dL, will be treated with 125 mg testosterone enanthate/week 5 mg finasteride/day for 1 year. We will assess the effects on body composition, 1-RM strength, grip strength, functional reach, bone mineral density, mood, cognition, hematopoiesis and prostate volume. We have chosen a moderately high dose of testosterone that may cause some adverse effects. We predict that finasteride will not block the anabolic effects of testosterone, but will block any prostate enlargement or symptoms and possibly other adverse effects as well.

Intervention(s) in this Clinical Trial

• Drug: Testosterone Enanthate
  • 125 mg, i.m. injection, once/week, for 52 weeks
• Behavioral: Collection of 3-day food logs with counseling of subjects
  • subject weighs food portions and completes food log, once/3 months, for 18 months (including 6-month follow-up. Counseling will be healthy ways to increase protein intake, if needed.
• Drug: Finasteride
  • 5 mg, oral, once/day, for 52 weeks
• Behavioral: Collection of 3-day food logs with counseling of subjects
  • subject weighs food portions and completes food log, once/3 months, for 18 months (including 6-month follow-up. Counseling will be healthy ways to increase protein intake, if needed.
• Drug: Testosterone Enanthate
  • 125 mg, i.m. injection, once/week, for 52 weeks
• Drug: Finasteride
  • 5 mg, oral, once/day, for 52 weeks
• Behavioral: Collection of 3-day food logs with counseling of subjects
  • subject weighs food portions and completes food log, once/3 months, for 18 months (including 6-month follow-up. Counseling will be healthy ways to increase protein intake, if needed.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • testosterone enanthate
• Experimental: 2
  • finasteride
• Experimental: 3
  • testosterone enanthate + finasteride
• Placebo Comparator: 4
  • placebo

Primary Measures

• 1-RM strength testing for 5 exercises will be performed using dynamic resistance exercise machines. Testing will be performed before treatment (baseline), at 3, 6, 9 and 12 months after treatment and at 3 months after completion of treatment.
  • Time Frame: baseline, 3 months, 6 months, 9 months, 12 months, 6 month followup
    Safety Issue?: No

Secondary Measures

• Grip strength in the dominant arm will be measured by using a Jamar dynamometer. Testing will be performed at baseline, after 3, 6, 9 and 12 months of treatment and at follow-up.
  • Time Frame: baseline, 3 months, 6 months, 9 months, 12 months, 6 month followup
    Safety Issue?: No
• Functional reach is measured as the furthest a subject can reach forward without taking a step. Testing will be performed at baseline, after 3, 6, 9 and 12 months of treatment and at follow-up.
  • Time Frame: baseline, 3 months, 6 months, 9 months, 12 months, 6 month followup
    Safety Issue?: No
• Dual x-ray absorptiometry (DXA): We will assess bone mineral density (BMD) and body composition using a fan-bean densitometer (Lunar Prodigy, GE Medical Systems).
  • Time Frame: baseline, 12 months
    Safety Issue?: No
• Geriatric Depression Scale (GDS): This 30-item, yes/no questionnaire will be administered at baseline, after 3, 6, 9 and 12 months of treatment and at follow-up.
  • Time Frame: baseline, 3 months, 6 months, 9 months, 12 months, 6 month followup
    Safety Issue?: No
• Rey Osterrieth Complex Figure (ROCF) test is a widely used standardized neuropsychological test for assessing visuospatial constructional functions, visuographic memory, and some aspects of planning.
  • Time Frame: baseline, 3 months, 6 months, 9 months, 12 months, 6 month followup
    Safety Issue?: No
• Trail-Making Test, Parts A&B (Trails A&B): is a standardized test of cognitive function which specifically assesses working memory, visual processing, visual spatial skills, selective and divided attention, and psychomotor coordination.
  • Time Frame: baseline, 3 months, 6 months, 9 months, 12 months, 6 month followup
    Safety Issue?: No
• Benton Judgment of Line Orientation Test is a standardized test with 30 items that is specific for visual spatial cognition. Tests will be administered at baseline, after 3, 6, 9 and 12 months of treatment and at follow-up.
  • Time Frame: baseline, 3 months, 6 months, 9 months, 12 months, 6 month followup
    Safety Issue?: Yes
• Blood analysis will be performed as follows: CBC (complete blood count), CMP (complete metabolic profile), Hgb A1C, LH, lipids, total testosterone, bioavailable testosterone and IGF-I.
  • Time Frame: baseline, 3 months, 6 months, 9 months, 12 months, 6 month followup
    Safety Issue?: No
• Dietary protein intake will be assessed using a 3-day food log and subjects will be counseled to increase protein intake if needed using the guide "Healthy Ways to Eat More Protein".
  • Time Frame: baseline, 3 months, 6 months, 9 months, 12 months, 6 month followup
    Safety Issue?: Yes
• Transrectal ultrasound sizing of prostate will be performed using the B&K Diagnostic System 3535, with 7MHz transrectal probe at baseline and after 6 and 12 months of treatment.
  • Time Frame: baseline, 6 month, 12 months
    Safety Issue?: No
• Life Satisfaction: is a written test of psychological well-being that will be performed at baseline, after 3, 6, 9 and 12 months of treatment and at follow-up.
  • Time Frame: baseline, 3 months, 6 months, 9 months, 12 months, 6 month followup
    Safety Issue?: No

Inclusion Criteria:

• Age > 60 years males
• Primary care at the Malcom Randall VA Medical Center in Gainesville, FL.
• Consenting subjects who have a morning (between 6:00 AM and 10:00 AM) serum total testosterone 300 ng/dL or bioavailable testosterone concentration 70 ng/dL and no exclusion criteria will be randomized to receive either testosterone or placebo.

Exclusion Criteria:

• Subjects with cognitive impairment will be identified by the Mini-Cog test and excluded. The Mini-Cog has high sensitivity and specificity for cognitive impairment, and is not affected by level of education.
• We will also exclude subjects with receptive aphasia, or a contraindication to testosterone replacement (i.e., history of or active prostate or breast cancer, severe benign prostatic hyperplasia (AUA SI > 25), congestive heart failure (Class 3 or 4), sleep apnea syndrome, polycythemia (Hct > 55%), or PSA > 2.6 ng/mL) will be excluded.
• Obese subjects (BMI > 35) will also be excluded.
• Subjects currently receiving testosterone supplementation or subjects who have an allergy to testosterone will also be excluded.
• Subjects previously receiving testosterone replacement therapy must be off such medication for at least four weeks.

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 60 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Department of Veterans Affairs

Overall Clinical Trial Officials and Contacts

Stephen Borst, PhD Principal Investigator North Florida/South Georgia Veterans Health System  

Overall Contact: Stephen Borst, PhD  stephen.borst@va.gov

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00475501

Study ID Number: ENDA-014-05F

ClinicalTrials.gov Identifier: NCT00475501

Health Authority: United States: Federal Government