Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| VA Merit Award | Other Grant/Funding Number | VHA AR6884R |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Endo USA Inc., a Keenova Therapeutics Company | INDUSTRY |
| Merck Sharp & Dohme LLC | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 | Experimental | testosterone enanthate |
|
| Arm 2 | Experimental | finasteride |
|
| Arm 3 | Experimental | testosterone enanthate + finasteride |
|
| Arm 4 | Placebo Comparator | placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Testosterone Enanthate | Drug | 125 mg, i.m. injection, once/week, for 52 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| 1 Repetition Maximum (1-RM) Strength Testing | 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. | baseline, 3 months, 6 months, 9 months, 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Grip Strength kg | 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. | baseline, 3 months, 6 months, 9 months, 12 months |
| Lumbar Spine L2-L4 Bone Mineral Density |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Stephen Borst, PhD | North Florida/South Georgia Veterans Health System | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| North Florida/South Georgia Veterans Health System | Gainesville | Florida | 32608 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24012740 | Result | 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. | |
| 24326421 | Result | 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. |
Not provided
Not provided
Subjects were excluded if they failed brief cognitive testing (MiniCog), if serum testosterone > 300 ng/dL or less and bio-testosterone > 70 ng/dL, congestive heart failure, sleep apnea, hematocrit (HCT) > 49%, prostate specific antigen (PSA) > 2.6 ng/ml, were taking coumadin or had orthopedic limitations.
Subjects were recruited between 7/2/2007 and 10/13/2010. Subjects responded to letters mailed to male patients aged 60 years or more who were seen at VA clinics.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1 | testosterone enanthate Testosterone Enanthate : 125 mg, i.m. injection, once/week, for 52 weeks 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. |
| FG001 | Arm 2 | finasteride 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. Finasteride : 5 mg, oral, once/day, for 52 weeks |
| FG002 | Arm 3 | testosterone enanthate + finasteride Testosterone Enanthate : 125 mg, i.m. injection, once/week, for 52 weeks Finasteride : 5 mg, oral, once/day, for 52 weeks 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. |
| FG003 | Arm 4 | placebo 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Men aged over 60 with serum testosterone 300 ng/dL or biotestosterone 70 ng/dL or less were recruited
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Testosterone Vehicle | 125 mg testosterone enanthate/week i.m. daily placebo pill |
| BG001 | Vehicle Finasteride | weekly vehicle injection 5 mg finasteride/day p.o. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 1 Repetition Maximum (1-RM) Strength Testing | 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. | per protocol | Posted | Mean | Standard Error | kg | baseline, 3 months, 6 months, 9 months, 12 months |
|
1 year
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1 | testosterone enanthate Testosterone Enanthate : 125 mg, i.m. injection, once/week, for 52 weeks |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Paget's disease | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| elevated prostate specific antigen | General disorders | Systematic Assessment | elevate PSA was defined as 2.6 or greater for study purposes |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Stephen Borst, Ph.D | Geriatric Research Education and Clinical Center | 352-374-6114 | 5033 | stephen.borst@va.gov |
Not provided
| ID | Term |
|---|---|
| D005058 | Eunuchism |
| D009133 | Muscular Atrophy |
| D055948 | Sarcopenia |
| D011470 | Prostatic Hyperplasia |
| ID | Term |
|---|---|
| D007006 | Hypogonadism |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D020879 | Neuromuscular Manifestations |
Not provided
Not provided
| ID | Term |
|---|---|
| C004648 | testosterone enanthate |
| D018120 | Finasteride |
| ID | Term |
|---|---|
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Finasteride | Drug | 5 mg, oral, once/day, for 52 weeks |
|
|
| Placebo | Other | Placebo |
|
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). |
| baseline, 12 months |
| Geriatric Depression Scale | 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 | baseline, 3 months, 6 months, 9 months, 12 months |
| 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | 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. | baseline, 3 months, 6 months, 9 months, 12 months |
| Trail-Making Test, Part A | 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. | baseline, 3 months, 6 months, 9 months, 12 months |
| Benton Judgment of Line Orientation Test | 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 | baseline, 3 months, 6 months, 9 months, 12 months |
| Hematocrit | Hematocrit was assessed as a part of routine blood analysis at the indicated time points. | baseline, 3 months, 6 months, 9 months, 12 months |
| Dietary Protein Intake | 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". | baseline, 3 months, 6 months, 9 months, 12 months |
| Transrectal Ultrasound Sizing of Prostate | 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. | baseline, 6 month, 12 months |
| Life Satisfaction | 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. | baseline, 3 months, 6 months, 9 months, 12 months |
| BG002 | Testosterone Finasteride | 125 mg testosterone enanthate/week i.m. 5 mg finasteride/day p.o. |
| BG003 | Vehicle Placebo | weekly vehicle injection daily placebo pill |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG002 | Arm 3 | testosterone enanthate + finasteride Testosterone Enanthate : 125 mg, i.m. injection, once/week, for 52 weeks Finasteride : 5 mg, oral, once/day, for 52 weeks Measurement of leg press strength, 1-RM |
| OG003 | Arm 4 | placebo Measurement of leg press strength, 1-RM |
|
|
|
| Secondary | Grip Strength kg | 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. | Posted | Mean | Standard Error | kg | baseline, 3 months, 6 months, 9 months, 12 months |
|
|
|
|
| Secondary | Lumbar Spine L2-L4 Bone Mineral Density | 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). | Posted | Mean | Standard Error | gm/cc | baseline, 12 months |
|
|
|
|
| Secondary | Geriatric Depression Scale | 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 | Posted | Mean | Standard Error | units on a scale | baseline, 3 months, 6 months, 9 months, 12 months |
|
|
|
|
| Secondary | 30 Minute Recall Portion of Rey Osterrieth Complex Figure (ROCF) Test | 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. | Posted | Mean | Standard Error | units on a scale | baseline, 3 months, 6 months, 9 months, 12 months |
|
|
|
|
| Secondary | Trail-Making Test, Part A | 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. | Posted | Mean | Standard Error | sec | baseline, 3 months, 6 months, 9 months, 12 months |
|
|
|
|
| Secondary | Benton Judgment of Line Orientation Test | 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 | Posted | Mean | Standard Error | units on a scale | baseline, 3 months, 6 months, 9 months, 12 months |
|
|
|
|
| Secondary | Hematocrit | Hematocrit was assessed as a part of routine blood analysis at the indicated time points. | Posted | Mean | Standard Error | % volume | baseline, 3 months, 6 months, 9 months, 12 months |
|
|
|
|
| Secondary | Dietary Protein Intake | 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". | Posted | Mean | Standard Error | gm/body weight (kg) | baseline, 3 months, 6 months, 9 months, 12 months |
|
|
|
|
| Secondary | Transrectal Ultrasound Sizing of Prostate | 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. | Posted | Mean | Standard Error | cc | baseline, 6 month, 12 months |
|
|
|
|
| Secondary | Life Satisfaction | 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. | Posted | Mean | Standard Error | points | baseline, 3 months, 6 months, 9 months, 12 months |
|
|
|
|
| 3 |
| 14 |
| 2 |
| 14 |
| EG001 | Arm 2 | finasteride Finasteride : 5 mg, oral, once/day, for 52 weeks | 2 | 13 | 1 | 13 |
| EG002 | Arm 3 | testosterone enanthate + finasteride Testosterone Enanthate : 125 mg, i.m. injection, once/week, for 52 weeks Finasteride : 5 mg, oral, once/day, for 52 weeks | 0 | 17 | 2 | 17 |
| EG003 | Arm 4 | placebo | 1 | 16 | 0 | 16 |
| knee pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| stroke | Vascular disorders | Systematic Assessment |
|
| sleep apnea | General disorders | Systematic Assessment |
|
| death | General disorders | Systematic Assessment | 83-year old subject did not show up for visits. We learned from the newspaper that he had dies, but did not learn the cause of death. |
|
| surgery for pre-existing heart condition | Cardiac disorders | Systematic Assessment | Subject had a pre-existing heart condition that did not preclude participation and thought that he might have surgery after the study. it was then decided to schedule the surgery sooner, so participation in the study stopped. |
|
|
| urinary symptoms | General disorders | Systematic Assessment | urinary symptoms defined as an increased score on urinary symptom questionaire |
|
| elevated hematocrit | Blood and lymphatic system disorders | Systematic Assessment | elevated hematocrit was defined as 54 or greater |
|
Not provided
| D009461 |
| Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D001284 | Atrophy |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
| D011469 | Prostatic Diseases |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D011083 |
| Polycyclic Compounds |
| D001378 | Azasteroids |
| D013260 | Steroids, Heterocyclic |
| change grip strength 3 month kg |
|
| change grip strength 6 month kg |
|
| change grip strength 9 month kg |
|
| change grip strength 12 month kg |
|
| change L2-L4 spine BMD 12 month gm/cc |
|
| depression 3 months |
|
| depression 6 months |
|
| depression 9 months |
|
| depression 12 months |
|
| Rey 3 month |
|
| Rey 6 month |
|
| Rey 9 month |
|
| Rey 12 month |
|
| Trails A 3 months |
|
| Trails A 6 months |
|
| Trails A 9 months |
|
| Trails A 12 months |
|
| Benton 3 months |
|
| Benton 6 months |
|
| Benton 9 months |
|
| Benton 12 months |
|
| change hematocrit 3 months % |
|
| change hematocrit 6 months % |
|
| change hematocrit 9 months % |
|
| change hematocrit 12 months % |
|
| protein intake 3 months |
|
| protein intake 6 months |
|
| protein intake 9 months |
|
| protein intake 12 months n = 1,1,2,5 |
|
| change prostate volume 6 months cc |
|
| change prostate volume 12 months cc |
|
| Life Satisfaction A 3 months |
|
| Life Satisfaction A 6 months |
|
| Life Satisfaction A 9 months |
|
| Life Satisfaction A 12 months |
|