Testosterone Plus Finasteride Treatment After Spinal Cord Injury

Phase 2

Terminated

Conditions: Spinal Cord Diseases
Spinal Cord Injury
Spinal Cord Injuries
Trauma, Nervous System
Wounds and Injuries
Central Nervous System Diseases
Nervous System Diseases
Gonadal Disorders
Endocrine System Diseases
Hypogonadism

Interventions: Drug: Testosterone Enanthate
Drug: Placebo injection
Drug: Finasteride
Drug: Placebo pill

Registration Number: NCT02248701

Lead Sponsor: VA Office of Research and Development

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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Male

Target Recruitment: 33

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
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)
Any angina that is not controlled on a current medical regimen (Canadian class II, III, or IV)
New York Heart Association (NYHA) class III or IV congestive heart failure
Systolic blood pressure >160 mmHg or diastolic blood pressure >100 mm Hg
Poorly controlled arrhythmia
Severe valvular disease
LDL cholesterol >160 mg/dl with known history of any major cardiovascular event, as defined above, within the last 12 months
Baseline EKG findings (e.g. left bundle branch block) or marked EKG abnormalities that would preclude serial screening for occult ischemic events
Current prostate, breast, or other organ cancer
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
Serum prostate-specific antigen (PSA) >3.0 ng/ml
History of benign prostate enlargement (BPE) >40cc, evaluated via TRUS
Hematocrit >47%
Liver enzymes (AST / ALT) above normal upper limit
Creatinine >1.4 mg/dL
Serum calcium >10.5 mg/dL
Gynecomastia
Mental state that precludes understanding of the protocol
Diagnosed, but untreated moderate or severe sleep apnea
Spinal nutrition screening tool score >15
Severe claustrophobia that precludes MRI testing
Current anticoagulant therapy
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
testosterone enanthate, finasteride	Testosterone Enanthate	Testosterone enanthate via i.m. injection (125 mg/week) and finasteride orally (5 mg/day)
testosterone enanthate, finasteride	Finasteride	Testosterone enanthate via i.m. injection (125 mg/week) and finasteride orally (5 mg/day)
placebo treatment	Placebo injection	Placebo via i.m. injection (once weekly) and placebo pill orally (daily)
placebo treatment	Placebo pill	Placebo via i.m. injection (once weekly) and placebo pill orally (daily)

Primary Outcome Measures

Name	Time	Method
Absolute Change in Walking Speed	Baseline, 6 months, 12 months	Absolute change in 10 m walking speed
Percent Change in Hip Bone Mineral Density	Baseline, 6 months, 12 months	Percent change in total hip bone mineral density of the non-dominant limb assessed via dual-energy X-ray absorptiometry (DXA)
Percent Changes in Muscle Cross-Sectional Area	Baseline, 6 months, 12 months	Percent Change in thigh (knee extensors) muscle cross-sectional area of the non-dominant limb assessed via MRI
Percent Change in Total Body Fat	Baseline, 6 months, 12 months	Percent change in total body fat assessed via dual-energy x-ray absorptiometry (DXA)

Secondary Outcome Measures

Name	Time	Method
Percent Change in Neuromuscular Function	Baseline, 6 months, 12 months	Percent change in thigh (knee extensors) peak isometric torque production of the non-dominant limb assessed via dynamometry
Percent Change in Visceral Fat	Baseline, 6 months, 12 months	Percent change in visceral (android) fat mass assessed via dual-energy x-ray absorptiometry (DXA)

Trial Locations

Locations (2): North Florida/South Georgia Veterans Health System, Gainesville, FL
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Gainesville, Florida, United States
James A. Haley Veterans' Hospital, Tampa, FL
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Tampa, Florida, United States