Clinical trial NCT02248701: Testosterone Plus Finasteride Treatment After Spinal Cord Injury
Official title: Higher-Than-Replacement Testosterone Plus Finasteride Treatment After SCI
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Keywords: 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
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: University of Florida
First posted: 2014-09-25
Enrollment: 33
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility 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
* 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

Primary outcomes:
measure: Percent Change in Hip Bone Mineral Density
timeFrame: Baseline, 6 months, 12 months
measure: Percent Changes in Muscle Cross-Sectional Area
timeFrame: Baseline, 6 months, 12 months
measure: Percent Change in Total Body Fat
timeFrame: Baseline, 6 months, 12 months
measure: Absolute Change in Walking Speed
timeFrame: Baseline, 6 months, 12 months
Secondary outcomes:
measure: Percent Change in Neuromuscular Function
timeFrame: Baseline, 6 months, 12 months
measure: Percent Change in Visceral Fat
timeFrame: Baseline, 6 months, 12 months
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: North Florida/South Georgia Veterans Health System, Gainesville, FL
state: Florida
city: Tampa
country: United States
facility: James A. Haley Veterans' Hospital, Tampa, FL
state: Florida
Study officials:
affiliation: North Florida/South Georgia Veterans Health System, Gainesville, FL
name: Joshua F Yarrow, PhD MS BS
role: PRINCIPAL_INVESTIGATOR
affiliation: North Florida/South Georgia Veterans Health System, Gainesville, FL
name: Dana M Otzel, PhD
role: PRINCIPAL_INVESTIGATOR
References: