Clinical trial NCT00475501: 5-Alpha Reductase and Anabolic Effects of Testosterone
Official title: 5-Alpha Reductase and Anabolic Effects of Testosterone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Male Hypogonadism
Muscle Atrophy
Sarcopenia
Benign Prostate Hypertrophy
Keywords: anabolic effects
finasteride
male hypogonadism
sarcopenia
testosterone
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Endo Pharmaceuticals
name: Merck Sharp & Dohme LLC
First posted: 2007-05-21
Enrollment: 60
Sex: MALE
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 1 Repetition Maximum (1-RM) Strength Testing
timeFrame: baseline, 3 months, 6 months, 9 months, 12 months
Secondary outcomes:
measure: Grip Strength kg
timeFrame: baseline, 3 months, 6 months, 9 months, 12 months
measure: Lumbar Spine L2-L4 Bone Mineral Density
timeFrame: baseline, 12 months
measure: Geriatric Depression Scale
timeFrame: baseline, 3 months, 6 months, 9 months, 12 months
measure: 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test
timeFrame: baseline, 3 months, 6 months, 9 months, 12 months
measure: Trail-Making Test, Part A
timeFrame: baseline, 3 months, 6 months, 9 months, 12 months
measure: Benton Judgment of Line Orientation Test
timeFrame: baseline, 3 months, 6 months, 9 months, 12 months
measure: Hematocrit
timeFrame: baseline, 3 months, 6 months, 9 months, 12 months
measure: Dietary Protein Intake
timeFrame: baseline, 3 months, 6 months, 9 months, 12 months
measure: Transrectal Ultrasound Sizing of Prostate
timeFrame: baseline, 6 month, 12 months
measure: Life Satisfaction
timeFrame: baseline, 3 months, 6 months, 9 months, 12 months
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: North Florida/South Georgia Veterans Health System
state: Florida
Study officials:
affiliation: North Florida/South Georgia Veterans Health System
name: Stephen Borst, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yarrow JF, Beck DT, Conover CF, Beggs LA, Goldberger BA, Borst SE. Invalidation of a commercially available human 5alpha-dihydrotestosterone immunoassay. Steroids. 2013 Dec 11;78(12-13):1220-5. doi: 10.1016/j.steroids.2013.08.013. Epub 2013 Sep 6.
citation: Borst SE, Yarrow JF, Conover CF, Nseyo U, Meuleman JR, Lipinska JA, Braith RW, Beck DT, Martin JS, Morrow M, Roessner S, Beggs LA, McCoy SC, Cannady DF 2nd, Shuster JJ. Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men: a randomized, controlled trial. Am J Physiol Endocrinol Metab. 2014 Feb 15;306(4):E433-42. doi: 10.1152/ajpendo.00592.2013. Epub 2013 Dec 10.