Testosterone Plus Finasteride Treatment After Spinal Cord Injury

Study Overview
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Brief Summary
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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
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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.

Official Title
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Higher-Than-Replacement Testosterone Plus Finasteride Treatment After SCI

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

Intervention / Treatment
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* Drug: Testosterone Enanthate
* Drug: Finasteride
* Drug: Placebo injection
* Drug: Placebo pill


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: testosterone enanthate, finasteride<br>Testosterone enanthate via i.m. injection (125 mg/week) and finasteride orally (5 mg/day) | Drug: Testosterone Enanthate<br>* Subjects receive testosterone (125 mg/week) by intramuscular injection<br>* Other names: delatestryl;Drug: Finasteride<br>* Subjects receive finasteride (5 mg/day) orally<br>* Other names: proscar;|
| Placebo Comparator: placebo treatment<br>Placebo via i.m. injection (once weekly) and placebo pill orally (daily) | Drug: Placebo injection<br>* Subjects receive placebo (weekly) by intramuscular injection<br>* Other names: sesame oil;Drug: Placebo pill<br>* Subjects receive placebo pill (daily) orally<br>* Other names: inactive substance;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Testosterone, Testosterone enanthate, Testosterone undecanoate, Testosterone 17 beta-cypionate, Methyltestosterone, Androgens, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiologic Effects of Drugs, Pharmacologic Actions, Antineoplastic Agents, Hormonal, Antineoplastic Agents, Therapeutic Uses, Anabolic Agents, Testosterone Replacement Therapy, Dual Energy X ray Absorptiometry, Lean Tissue Mass, Body Composition, Lipid and Glucose profile, Muscle Strength, 5-alpha Reductase, Muscle Mass, Bone Mineral Density, Adipose Tissue, Body Fat, Density, Bone, Bone Formation, Bone Resorption, Bone Density Conservation Agents, Magnetic Resonance Imaging, Muscle, Skeletal, Bone and Bones, Gait, Walking, Locomotion, Motor Activity