Testosterone Plus Finasteride Treatment After Spinal Cord Injury

Higher-Than-Replacement Testosterone Plus Finasteride Treatment After SCI

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.

Study Overview

• Status: Terminated
• Conditions: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Endocrine System Diseases; Gonadal Disorders; Trauma, Nervous System; Spinal Cord Diseases; Hypogonadism; Spinal Cord Injuries; Spinal Cord Injury; Genital Diseases, Male
• Intervention / Treatment: Drug: Testosterone Enanthate; Drug: Finasteride; Drug: Placebo injection; Drug: Placebo pill

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 Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • North Florida/South Georgia Veterans Health System, Gainesville, FL
    • Tampa, Florida, United States, 33612
      • James A. Haley Veterans' Hospital, Tampa, FL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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: delatestryl; Drug: Finasteride; Subjects receive finasteride (5 mg/day) orally; Other Names: proscar
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; Other Names: sesame oil; Drug: Placebo pill; Subjects receive placebo pill (daily) orally; Other Names: inactive substance

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: University of Florida
• Investigators: Principal Investigator: Joshua F Yarrow, PhD MS BS, North Florida/South Georgia Veterans Health System, Gainesville, FL; Principal Investigator: Dana M Otzel, PhD, North Florida/South Georgia Veterans Health System, Gainesville, FL

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2017
• Primary Completion (Actual): August 13, 2021
• Study Completion (Actual): August 13, 2021

Study Registration Dates

• First Submitted: September 22, 2014
• First Submitted That Met QC Criteria: September 22, 2014
• First Posted (Estimated): September 25, 2014

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Gait; Magnetic Resonance Imaging; Body Composition; Walking; Muscle Strength; Antineoplastic Agents; Motor Activity; Pharmacologic Actions; Locomotion; Therapeutic Uses; Testosterone; Bone Density Conservation Agents; Muscle Mass; Androgens; Hormones; Bone Formation; Adipose Tissue; Bone and Bones; Antineoplastic Agents, Hormonal; Bone Mineral Density; Body Fat; Testosterone enanthate; Testosterone undecanoate; Testosterone 17 beta-cypionate; Methyltestosterone; Hormone Substitutes, and Hormone Antagonists; Physiologic Effects of Drugs; Anabolic Agents; Testosterone Replacement Therapy; Dual Energy X ray Absorptiometry; Lean Tissue Mass; Density, Bone; Bone Resorption; 5-alpha Reductase; Lipid and Glucose profile; Muscle, Skeletal
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Wounds and Injuries; Nervous System Diseases; Hypogonadism; Spinal Cord Diseases; Spinal Cord Injuries; Endocrine System Diseases; Trauma, Nervous System; Gonadal Disorders; Central Nervous System Diseases; Genital Diseases; Genital Diseases, Male; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Urological Agents; Enzyme Inhibitors; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Steroid Synthesis Inhibitors; Androgens; 5-alpha Reductase Inhibitors; Anabolic Agents; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate; Finasteride
• Other Study ID Numbers: B1449-R; 1I01RX001449-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared according to the requirements described by the Department of Veterans Affairs, Office of Research & Development.
• IPD Sharing Time Frame: Data will be shared according to the requirements described by the Department of Veterans Affairs, Office of Research & Development.
• IPD Sharing Access Criteria: Data will be shared according to the requirements described by the Department of Veterans Affairs, Office of Research & Development.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No