Overview

Locomotor Training With Testosterone to Promote Bone and Muscle Health After Spinal Cord Injury

Status:
Recruiting
Trial end date:
2023-01-30
Target enrollment:
0
Participant gender:
Male
Summary
This pilot study will determine the feasibility of implementing a combinatory rehabilitation strategy involving testosterone replacement therapy (TRT) with locomotor training (LT; walking on a treadmill with assistance and overground walking) in men with testosterone deficiency and walking dysfunction after incomplete spinal cord injury. The investigators hypothesize that LT+TRT treatment will improve muscle size, muscle function, bone mineral density, and walking speed.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
North Florida Foundation for Research and Education
Collaborators:
Brooks Rehabilitation
North Florida/South Georgia Veterans Health System
University of Florida
Treatments:
Methyltestosterone
Testosterone
Testosterone 17 beta-cypionate
Testosterone enanthate
Testosterone undecanoate
Criteria
Inclusion Criteria:

- Men >18 years of age

- Diagnosis of an incomplete SCI involving spinal segments T12 or above, for >12-months

- Low serum total testosterone (<300 ng/dL), bioavailable testosterone (<75 ng/dL), or
free testosterone (<64 ng/dL)

- Presence of one or more sign or symptom that may be related to low testosterone,
including: loss of body hair or reduced shaving, very small testes (<6 mL), reduced
sexual desire (libido) and activity, decreased spontaneous erections (e.g., morning
erections) or erectile dysfunction, breast discomfort or gynecomastia, height loss,
low-trauma fracture, or low BMD, hot flushes or sweats, decreased energy, motivation,
initiative, or self-confidence, fatigue or irritability, feeling sad or blue, having a
depressed mood, or having a persistent low-grade depressive disorder, poor
concentration or memory, sleep disturbances or increased sleepiness, mild unexplained
anemia (normochromic or normocytic), reduced muscle bulk, strength, or physical
performance, Increased body fat or body mass index, any other sign or symptom commonly
associated with low testosterone

- Locomotor dysfunction

- Diagnosis of first time SCI including etiology from trauma, vascular, or orthopedic
pathology

- Medically-stable condition that is asymptomatic for conditions that will interfere
with the study participation

- Willingness to administer TRT as instructed by the study staff and to abide by study
protocol

- Documented approval from the study physician verifying medical status

Exclusion Criteria:

- Currently participating in another research protocol that may influence study
outcomes.

- Mental state that precludes understanding the study protocol.

- Life expectancy <12-months.

- History of or current congenital SCI (e.g., Chiari malformation, myelomeningocele,
intraspinal neoplasm, Frederich's ataxis) or other degenerative spinal disorder (e.g.,
spinocerebellar degeneration, syringomyelia) that may complicate study procedures

- Multiple sclerosis, amyotrophic lateral sclerosis, or other neurologic impairment or
injury

- Current prostate, breast, or other organ cancer or a history of prostate or breast
cancer

- Any other diagnosed or treated cancer within the past 24-months, with the exceptions
of basal or squamous cell carcinoma of the skin that has been successfully treated

- Serum prostate-specific antigen (PSA) >3.0 ng/mL [men treated with 5-alpha reductase
inhibitors (e.g., finasteride or dutasteride) are eligible to participate if PSA
values are ≤1.5 ng/mL]

- Prostate nodule or induration noted on digital rectal exam (DRE) during screening that
tests positive for prostate cancer

- Currently seeking fertility or expected during the duration of the study

- Gynecomastia

- Hematocrit (HCT) >49%

- Any major cardiovascular (CV) 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, revascularization of the
carotid or middle cerebral artery or procedures to treat critical limb ischemia, or
hospitalization due to unstable angina, transient ischemic attack, stroke, or
peripheral vascular disease)

- Angina that is not controlled on a current medical regimen (Canadian class II, III, or
IV)

- Poorly compensated congestive heart failure (NYHA class III or IV)

- Poorly controlled hypertension (consistently measured systolic BP ≥160 mmHg or
diastolic BP ≥100 mmHg), while on medications

- Poorly controlled arrhythmia of any type

- Severe valvular heart disease

- Baseline electrocardiogram (ECG) findings such as left bundle branch block or marked
ECG abnormalities that would preclude serial screening evaluations for occult ischemic
events

- History of unprovoked deep venous thrombosis (DVT), unprovoked pulmonary embolism,
history of recurrent DVT or known thrombophilia

- LDL cholesterol >160 mg/dL with history of any major CV event, defined above, within
the last 12-months

- Major non-CV surgery (e.g., major abdominal or thoracic procedure) within 90-days
prior to screening and/or a major surgery scheduled at the time of screening

- Liver enzymes (AST or ALT) >1.5 times the normal upper limit

- Severe or end-stage chronic kidney disease documented by estimated glomerular
filtration rate (eGFR) <30 mL/min

- Diagnosed, but untreated severe obstructive sleep apnea

- Lower extremity fracture in the last 12-months (exclusion criterion for participation
in LT+TRT group only)

- Femoral neck, total hip, or lumbar spine t-score below -2.5 or distal femur BMD <0.70
g/cm2, assessed via DEXA at screening (exclusion criterion for participation in LT+TRT
group only)

- Current anticoagulant therapy (contraindication for i.m. injections)

- Use of any of the following pharmacologic agents in the previous 90-days: any TRT
formulation, any compounded or over-the-counter androgenic hormones or androgen
precursors, clomiphene, aromatase inhibitors, anti-estrogen or estrogen treatment, or
growth hormone

- Use of anti-resorptive or bone anabolic drug therapy in the previous 180-days

- Acute use (>5-days) of any opioids (e.g., oxycodone, hydrocodone, etc) or systemic
glucocorticoids >7.5 mg/d prednisone equivalent (e.g., hydrocortisone 30 mg,
methylprednisolone 6 mg, or dexamethasone 1.2 mg) within 1-week before screening
visit, except men who are taking these medications for a chronic condition and are
anticipated to continue treatment for the study duration

- Known allergy to any component of the TRT formulation (e.g., sesame oil)

- Any other condition, therapy, lab abnormality, medical or psychiatric conditions, 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 study intervention, or
interfere with the person's ability to participate for the entire study duration