Testosterone Therapy With or Without Finasteride After Spinal Cord Injury: TRT-SCI Trial (TRT-SCI)

Inclusion Criteria:

• Veterans eligible for care within the Veterans Health Administration (VHA)
• Diagnosis of motor incomplete SCI (AIS C-D) for >24-months involving spinal segment lumbar (L)1 or above from trauma, vascular, or orthopedic pathology
• Low total testosterone (<300 nanograms/decilliter [ng/dL]) and/or low free testosterone (<4.6 ng/dL)

• Presence of one or more sign of low testosterone, defined as:

  • decreased energy
  • motivation
  • initiative or self-confidence
  • increased fatigue or tiredness
  • reduced sexual desire or activity
  • decreased spontaneous (e.g., morning) erections or erectile dysfunction
  • loss of body hair or reduced shaving
  • feeling sad or blue or having a depressed mood or a persistent low-grade depressive disorder (defined as a score of >3 on the Patient Health Questionnaire [PHQ]-2)
  • hot flashes
  • fatigue or irritability
  • poor concentration or memory
  • mild unexplained (normocytic-normochromic) anemia, defined as hematocrit (HCT) <40%, hemoglobin <13.6 grams/deciliter (g/dL), or red blood cell count <4.5 million/microliter (mcL)
  • sleep disturbances or increased sleepiness
  • reduced muscle bulk, strength, or physical function
  • increased body fat or body mass index
• Presence of motor impairment, defined as self-selected walking pace ≤1.0 meters/second (m/s) on a 10-meter walk test (10mWT), with or without gait devices or braces and with or without assistance from another person, or as self-selected walking pace >1.0 m/s with reliance on a gait device or brace or with highly compensated movement impairment identified by a trained observer
• Medically stable condition asymptomatic for bladder infection, major decubiti, cardiopulmonary disease, or other significant condition that will interfere with the study
• Documented approval from a physician verifying medical status

Exclusion Criteria:

• Involvement in another research study that may influence outcomes
• Mental state that precludes understanding the protocol
• Life expectancy <12 months
• History of or current congenital spinal cord injury (SCI) (e.g., Chiari malformation, myelomeningocele, intraspinal neoplasm, Friedreich's ataxia) or degenerative spinal disorder (e.g., spinocerebellar degeneration) that may complicate procedures
• Amyotrophic lateral sclerosis, multiple sclerosis, or other neurologic injury / impairment that may complicate procedures
• Current cancer diagnosis
• History of prostate or breast cancer
• Any diagnosed or treated cancer in the past 24 months, except basal or squamous cell carcinoma of the skin that has been successfully treated
• Any major lower-limb fracture in the past 12 months
• Unevaluated circulating prostate-specific antigen (PSA) >4.0 nanograms/milliliter (ng/mL) or >3.0 ng/mL in men with prostate cancer risk factors, including agent orange exposure, first degree relative with prostate cancer, or African American background
• Currently seeking fertility or expected during the study
• Diagnosed gynecomastia
• Hematocrit (HCT) >48%

• Any major cardiovascular event in the last 6 months, defined as:

  • an acute myocardial infarction
  • any cardiac revascularization procedure including stenting
  • angioplasty or coronary artery bypass grafting
  • revascularization of the carotid or middle cerebral artery or procedure to treat critical limb ischemia
  • hospitalization due to unstable angina
  • transient ischemic attack
  • stroke
  • peripheral vascular disease
• Any angina that is not controlled on a current medical regimen (Canadian class II, III, or IV)
• Poorly compensated congestive heart failure (New York Heart Association [NYHA] class III or IV)
• Poorly controlled hypertension when on medication (consistent systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg)
• Poorly controlled arrhythmia of any type
• Severe valvular heart disease
• Baseline electrocardiogram findings such as left bundle branch block or marked abnormality that precludes serial screening for occult ischemic events
• History of unprovoked deep venous thrombosis, unprovoked pulmonary embolism, history of recurrent deep venous thrombosis or known thrombophilia
• Major non-cardiovascular surgery (e.g., major abdominal or thoracic procedure) within 90 days before screening or a major surgery scheduled at the time of screening
• Liver enzymes (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) >1.5 times the normal upper limit
• Severe or end-stage chronic kidney disease defined as eGFR <30 milliliters/minute (mL/min)
• Diagnosed, but untreated severe obstructive sleep apnea
• Use of an agent that alters sex-steroid metabolism in the past 90 days, such as: testosterone therapy (TRT), compounded or over-the-counter androgenic hormone or androgen precursor, 5-alpha reductase (5AR) inhibitors, growth hormone, clomiphene, aromatase inhibitors, anti-estrogen or estrogen treatment, or others
• Use of anti-resorptive or bone anabolic drug therapy in the past 180 days
• Acute use (>5 days) of any opioid (e.g., oxycodone, hydrocodone) or systemic glucocorticoids >7.5 milligrams (mg)/day prednisone equivalent (e.g., hydrocortisone 30 mg, methylprednisolone 6 mg, or dexamethasone 1.2 mg) in the week before screening, except for men who are taking these for a chronic condition and who are anticipated to continue these for the study duration
• Known allergy to any TRT component (e.g., cottonseed oil or other)
• Any other condition, lab abnormality, therapy, medical or psychiatric condition, or reason that might pose a risk to the participant, make participation not in the person's best interest, confound the study results (e.g., inability to comply with study requirements), make the participant unsuitable to receive a study intervention, or interfere with their ability to participate for the full study duration