Testosterone Plus Finasteride Treatment After Spinal Cord Injury

Spinal Cord Injuries Clinical Trial

Official title:

Higher-Than-Replacement Testosterone Plus Finasteride Treatment After SCI

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02248701
• Other study ID #: B1449-R
• Secondary ID: 1I01RX001449-01A
• Status: Terminated
• Phase: Phase 2
• Start date: April 27, 2017
• Est. completion date: August 13, 2021

Study information

• Verified date: September 2023
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 33
• Est. completion date: August 13, 2021
• Est. primary completion date: August 13, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Testosterone Enanthate
Subjects receive testosterone (125 mg/week) by intramuscular injection
• Finasteride
Subjects receive finasteride (5 mg/day) orally
• Placebo injection
Subjects receive placebo (weekly) by intramuscular injection
• Placebo pill
Subjects receive placebo pill (daily) orally

Locations

Country	Name	City	State
United States	North Florida/South Georgia Veterans Health System, Gainesville, FL	Gainesville	Florida
United States	James A. Haley Veterans' Hospital, Tampa, FL	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
VA Office of Research and Development	University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Absolute Change in Walking Speed	Absolute change in 10 m walking speed	Baseline, 6 months, 12 months
Secondary	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
Secondary	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