5-Alpha Reductase and Anabolic Effects of Testosterone

Phase 2

Completed

Conditions: Male Hypogonadism
Muscle Atrophy
Sarcopenia
Benign Prostate Hypertrophy

Interventions: Other: Placebo
Drug: Finasteride
Drug: Testosterone Enanthate

Registration Number: NCT00475501

Lead Sponsor: VA Office of Research and Development

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 Description: 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 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 60

Inclusion Criteria

Age > 60 years males
Primary care at the Malcolm Randall VA Medical Center in Gainesville, Florida.
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 as assessed by elevated American Urologic Association Symptom Index (AUASI) score > 25), congestive heart failure (Class 3 or 4), sleep apnea syndrome, polycythemia (Hct > 55%), or prostate specific antigen (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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Arm 4	Placebo	placebo
Arm 2	Finasteride	finasteride
Arm 1	Testosterone Enanthate	testosterone enanthate
Arm 3	Finasteride	testosterone enanthate + finasteride
Arm 3	Testosterone Enanthate	testosterone enanthate + finasteride

Primary Outcome Measures

Name	Time	Method
1 Repetition Maximum (1-RM) Strength Testing	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.

Secondary Outcome Measures

Name	Time	Method
Benton Judgment of Line Orientation Test	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
Geriatric Depression Scale	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
Trail-Making Test, Part A	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.
Hematocrit	baseline, 3 months, 6 months, 9 months, 12 months	Hematocrit was assessed as a part of routine blood analysis at the indicated time points.
Grip Strength kg	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	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).
30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test	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.
Life Satisfaction	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.
Dietary Protein Intake	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	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.