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

Sponsor

North Florida Foundation for Research and Education (Other)

Overall Status

Recruiting

CT.gov ID

NCT04460872

Collaborator

North Florida/South Georgia Veterans Health System (Other), Brooks Rehabilitation (Other), University of Florida (Other)

Enrollment

Locations

Arms

Anticipated Duration (Months)

10.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Spinal Cord Injury Spinal Cord Injuries Trauma, Nervous System Wounds and Injury Central Nervous System Diseases Spinal Cord Diseases Gonadal Disorders Endocrine System Diseases Hypogonadism Genital Diseases, Male Spinal Cord Trauma Injuries, Spinal Cord Walking, Difficulty Gait Disorders, Neurologic Locomotion Disorder, Neurologic Wounds and Injuries Nervous System Diseases Testosterone Deficiency Androgen Deficiency Hormone Deficiency	Drug: Testosterone Enanthate Behavioral: Locomotor Training	Phase 2

Detailed Description

Spinal cord injury (SCI) produces bone, muscle, and neural impairments that increase fracture risk and impede recovery of physical function. Locomotor training (LT) increases muscle size and promotes recovery of muscle function and walking in some persons with incomplete SCI. It is unknown if testosterone replacement therapy (TRT) improves these factors in men who have walking dysfunction and low testosterone after incomplete SCI. In addition, the combined effects of LT plus TRT remain unknown in men with incomplete SCI.

For this pilot study, men with incomplete SCI who have low testosterone and walking dysfunction will receive 6-months of TRT alone or TRT with LT. TRT injections will be given weekly. LT will involve 35 sessions of treadmill walking with assistance and overground walking (4 sessions per week) during the initial 2-3 months of TRT. Participants will be assessed at study entry and at 1-6 month intervals thereafter. Testing will include measurements such as a magnetic resonance imaging (MRI) scans, dual energy x-ray absorptiometry (DEXA) scan, and muscle performance and walking tests. Participants will also undergo safety tests, including physical exams, electrocardiogram (ECG), prostate digital rectal exam, and blood tests to assess hematocrit, liver enzymes (AST and ALT), prostate specific antigen (PSA), and other health markers. The treatment groups will be compared with a non-treatment control group comprised of men with incomplete SCI who receive no treatment. Participants enrolled in the non-treatment control group will undergo the same tests described above.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

21 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

Locomotor Training With Testosterone to Promote Bone and Muscle Health

Actual Study Start Date :

Jan 31, 2021

Anticipated Primary Completion Date :

Jan 30, 2023

Anticipated Study Completion Date :

Jan 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: testosterone enanthate Testosterone enanthate via i.m. injection (100 mg/week)	Drug: Testosterone Enanthate Subjects receive testosterone (100 mg/week) by intramuscular injection Other Names: delatestryl
Experimental: locomotor training, testosterone enanthate Treadmill and overground walking training and testosterone enanthate via i.m. injection (100 mg/week)	Drug: Testosterone Enanthate Subjects receive testosterone (100 mg/week) by intramuscular injection Other Names: delatestryl Behavioral: Locomotor Training Subjects receive locomotor training (4 sessions/week for 2-3 months) Other Names: Treadmill training and overground walking
No Intervention: non-interventional control Non-interventional control group

Arm

Intervention/Treatment

Experimental: testosterone enanthate

Testosterone enanthate via i.m. injection (100 mg/week)

Drug: Testosterone Enanthate

Subjects receive testosterone (100 mg/week) by intramuscular injection

Other Names:

delatestryl

Experimental: locomotor training, testosterone enanthate

Treadmill and overground walking training and testosterone enanthate via i.m. injection (100 mg/week)

Drug: Testosterone Enanthate

Subjects receive testosterone (100 mg/week) by intramuscular injection

Other Names:

delatestryl

Behavioral: Locomotor Training

Subjects receive locomotor training (4 sessions/week for 2-3 months)

Other Names:

Treadmill training and overground walking

No Intervention: non-interventional control

Non-interventional control group

Outcome Measures

Primary Outcome Measures

change in thigh muscle cross-sectional area [baseline, 3 months, 6 months]
change in thigh muscle cross-sectional area assessed via MRI
change in 6 min walk test (6MWT) [baseline, 1 month, 3 months, 6 months]
change in distance covered on 6MWT
change in distal femur bone mineral density [baseline, 3 months, 6 months]
change in distal femur bone mineral density (BMD) assessed via DEXA

Secondary Outcome Measures

change in knee extensor peak torque [baseline, 3 months, 6 months]
change in knee extensor peak torque assessed via dynamometry
change in 10m walk test (10mWT) [baseline, 1 month, 3 months, 6 months]
change in time to complete 10mWT
change in bone resorption marker [baseline, 3 months, 6 months]
change in circulating bone resorption marker
change in bone formation marker [baseline, 3 months, 6 months]
change in circulating bone formation marker

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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