Clinical Trial: 5-Alpha Reductase and Anabolic Effects of Testosterone

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary:

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- repetition maximum (1-RM) strength, grip strength, functional reach, bone mineral
Sponsor: VA Office of Research and Development

Current Primary Outcome: 1 Repetition Maximum (1-RM) Strength Testing [ Time Frame: baseline, 3 months, 6 months, 9 months, 12 months ]

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.


Original Primary Outcome:

  • 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.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • Blood analysis will be performed as follows:

    Current Secondary Outcome:

    • Grip Strength kg [ Time Frame: baseline, 3 months, 6 months, 9 months, 12 months ]
      Grip strength in the dominant arm will be measured by using a dynamometer. Testing will be performed at baseline, after 3, 6, 9 and 12 months of treatment.
    • Lumbar Spine L2-L4 Bone Mineral Density [ Time Frame: baseline, 12 months ]
      Dual x-ray absorptiometry (DXA): We will assess bone mineral density (BMD) and body composition using a fan-bean densitometer (Lunar Prodigy, General Electric Medical Systems).
    • Geriatric Depression Scale [ Time Frame: baseline, 3 months, 6 months, 9 months, 12 months ]

      Geriatric Depression Scale (GDS): This 15-item, yes/no questionnaire will be administered at baseline, after 3, 6, 9 and 12 months of treatment.

      The minimum score is 0 = no depressive symptoms The maximum score is 15 = a very high level of depressive symptoms

    • 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test [ Time Frame: baseline, 3 months, 6 months, 9 months, 12 months ]

      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.

      The drawing is scored by a blinded neuropsychologist on a scale of 0 to 30 with 30 representing a perfect drawing.

    • Trail-Making Test, Part A [ Time Frame: baseline, 3 months, 6 months, 9 months, 12 months ]
      Trail-Making Test, Part A: is a standardized test of cognitive function which specifically assesses working memory, visual processing, visual spatial skills, selective and divided attention, and psychomotor coordination. the test is scored as seconds required to successful completion of the task with a lower score representing better performance. The mean score on test is 30.75 second with a standard deviation of 16.27.
    • Benton Judgment of Line Orientation Test [ Time Frame: baseline, 3 months, 6 months, 9 months, 12 months ]

      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.

      The minimum score is 0, indicating low visual spatial cognition. The maximum score is 30, indicating high visual spatial cognition

    • Hematocrit [ Time Frame: baseline, 3 months, 6 months, 9 months, 12 months ]
      Hematocrit was assessed as a part of routine blood analysis at the indicated time points.
    • Dietary Protein Intake [ Time Frame: baseline, 3 months, 6 months, 9 months, 12 months ]
      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".
    • Transrectal Ultrasound Sizing of Prostate [ Time Frame: baseline, 6 month, 12 months ]
      Transrectal ultrasound sizing of prostate will be performed using the B&K Diagnostic System 3535, with 7 mega hertz transrectal probe at baseline and after 6 and 12 months of treatment.
    • Life Satisfaction [ Time Frame: baseline, 3 months, 6 months, 9 months, 12 months ]
      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. This is a 20-point scale, with a possible range of scores from 0 to 20. A higher score represents greater life satisfaction.


    Original Secondary Outcome:

    • 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".
    • 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.
    • 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.


    Information By: VA Office of Research and Development

    Dates:
    Date Received: April 16, 2007
    Date Started: January 2007
    Date Completion:
    Last Updated: December 4, 2014
    Last Verified: December 2014