Testosterone Plus Finasteride Treatment After Spinal Cord Injury
Study Details
Study Description
Brief Summary
The purpose of this study is to determine whether testosterone plus finasteride treatment will improve musculoskeletal health, neuromuscular function, body composition, and metabolic health in hypogonadal men who have experienced ambulatory dysfunction subsequent to incomplete spinal cord injury. The investigators hypothesize that this treatment will improve bone mineral density, enhance muscle size and muscle function, and improve body composition, without causing prostate enlargement.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Men with spinal cord injury (SCI) experience a high prevalence of hypogonadism which influences the neural, muscular, skeletal, and body composition deficits that occur after injury. It remains unknown whether testosterone administration improves bone mineral density, muscle mass and muscle function, and body composition / metabolic health in hypogonadal men who have experienced ambulatory dysfunction subsequent to incomplete spinal cord injury. In addition, it is unknown whether testosterone or the 5-alpha reduced metabolite dihydrotestosterone (an endogenous metabolite of testosterone) mediate effects in these and other tissues.
For this study hypogonadal men with motor incomplete spinal cord injury who present with ambulatory dysfunction will be randomized to receive testosterone plus the 5-alpha reductase inhibitor finasteride or a placebo treatment for 12 months. Testosterone or placebo injection will be administered weekly; finasteride or placebo will be administered daily. Participants will be assessed at study entry and at 1-6 month intervals thereafter. Assessments will include measurements such as a dual energy x-ray absorptiometry (DEXA) scan, MRI scan, and muscle performance tests. Participants will also have several safety tests, including electrocardiogram (EKG) for cardiac electrophysiology, prostate digital rectal exam and prostate ultrasound sizing for prostate health, and blood tests to assess hematocrit, liver enzymes (AST and ALT), prostate specific antigen (PSA), cholesterol, and other health markers.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: testosterone enanthate, finasteride Testosterone enanthate via i.m. injection (125 mg/week) and finasteride orally (5 mg/day) |
Drug: Testosterone Enanthate
Subjects receive testosterone (125 mg/week) by intramuscular injection
Other Names:
Drug: Finasteride
Subjects receive finasteride (5 mg/day) orally
Other Names:
|
| Placebo Comparator: placebo treatment Placebo via i.m. injection (once weekly) and placebo pill orally (daily) |
Drug: Placebo injection
Subjects receive placebo (weekly) by intramuscular injection
Drug: Placebo pill
Subjects receive placebo pill (daily) orally
|
Outcome Measures
Primary Outcome Measures
- Change in Hip Bone Mineral Density [Baseline, 6 months, 12 months]
Change in hip bone mineral density assessed via dual-energy X-ray absorptiometry (DXA)
- Changes in Muscle Cross-Sectional Area [Baseline, 6 months, 12 months]
Change in thigh muscle cross-sectional area assessed via MRI
- Change in Total Body Fat [Baseline, 6 months, 12 months]
Change in total body fat assessed via DXA
- Change in Walking Speed [Baseline, 6 months, 12 months]
Change in 10 m walking speed
Secondary Outcome Measures
- Change in Neuromuscular Function [Baseline, 6 months, 12 months]
Change in thigh muscle force production assessed via dynamometry
- Change in Visceral Fat [Baseline, 6 months, 12 months]
Change in visceral fat mass assessed via DXA
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male > 18 years of age
-
Traumatic, vascular, or orthopedic spinal cord injury between C2-L3 >12 months prior to enrollment
-
Motor incomplete spinal cord (AIS C/D)
-
Ambulatory dysfunction
-
Medically stable condition that is asymptomatic for bladder infection, decubiti, cardiopulmonary disease, or other significant medical conditions
-
Serum total testosterone (<325 ng/dL) or bioavailable testosterone (<70 ng/dL)
Exclusion Criteria:
-
Currently participating in another research protocol that may influence study outcomes
-
Life expectancy <1 year
-
History of or current congenital spinal cord injury or other degenerative spinal disorder
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Diagnosis of multiple sclerosis, amyotrophic lateral sclerosis, or other neurologic impairment/injury
-
History of venous thromboembolism within the last 6 months, specifically deep venous thromboembolism and pulmonary embolism, history of recurrent venous thromboembolism or know hereditary thrombophilia
-
Poorly compensated or uncontrolled cardiovascular disease
-
Any major cardiovascular event within the last 12 months (defined as a history of acute myocardial infarction, any cardiac revascularization procedure including angioplasty, stenting, or coronary artery bypass grafting, hospitalization due to unstable angina, transient ischemic attack, or stroke)
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Any angina that is not controlled on a current medical regimen (Canadian class II, III, or IV)
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New York Heart Association (NYHA) class III or IV congestive heart failure
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Systolic blood pressure >160 mmHg or diastolic blood pressure >100 mm Hg
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Poorly controlled arrhythmia
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Severe valvular disease
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LDL cholesterol >160 mg/dl with known history of any major cardiovascular event, as defined above, within the last 12 months
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Baseline EKG findings (e.g. left bundle branch block) or marked EKG abnormalities that would preclude serial screening for occult ischemic events
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Current prostate, breast, or other organ cancer
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History of prostate, breast, or other organ cancer, with the exceptions of completely resolved basal or squamous cell carcinoma for a duration of >24 months or completely resolved melanoma for a duration of >24 months
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Serum prostate-specific antigen (PSA) >3.0 ng/ml
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History of benign prostate enlargement (BPE) >40cc, evaluated via TRUS
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Hematocrit >47%
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Liver enzymes (AST / ALT) above normal upper limit
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Creatinine >1.4 mg/dL
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Serum calcium >10.5 mg/dL
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Gynecomastia
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Mental state that precludes understanding of the protocol
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Diagnosed, but untreated moderate or severe sleep apnea
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Spinal nutrition screening tool score >15
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Severe claustrophobia that precludes MRI testing
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Current anticoagulant therapy
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Use of any of the following pharmacologic agents in the previous 3 months (testosterone, leuprolide, androgenic hormones, growth hormone, oral androgen precursors, 5-alpha reductase or aromatase inhibitors)
-
Use of anti-resorptive or bone anabolic drug therapy in the previous 6 months
-
Known allergy to sesame oil
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | James A. Haley Veterans' Hospital, Tampa, FL | Tampa | Florida | United States | 33612 |
| 2 | North Florida/South Georgia Veterans Health System, Gainesville, FL | Gainesville | Georgia | United States | 32608 |
Sponsors and Collaborators
- VA Office of Research and Development
- University of Florida
Investigators
- Principal Investigator: Joshua F Yarrow, PhD MS BS, North Florida/South Georgia Veterans Health System, Gainesville, FL
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- B1449-R
- 1I01RX001449-01A1