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

NCT04460872 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 649726
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

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 or complete spinal cord injury. The investigators hypothesize that LT+TRT treatment will improve muscle size and bone mineral density in men with low T and ambulatory dysfunction after incomplete or complete SCI, along with muscle fundtion and walking recovery in men with T low and ambulatory dysfunction ater incomplete SCI.

Conditions

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

Keywords

Testosterone; Testosterone enanthate; Testosterone undecanoate; Testosterone 17 beta-cypionate; Methyltestosterone; Androgens; Hormones; Hormone Substitutes, and Hormone Antagonists; Physiologic Effects of Drugs; Pharmacologic Actions; Therapeutic Uses; Anabolic Agents; Testosterone Replacement Therapy; Dual Energy X ray Absorptiometry; Lean Tissue Mass; Body Composition; Muscle Strength; Muscle Mass; Bone Mineral Density; Adipose Tissue; Body Fat; Density, Bone; Bone Formation; Bone Resorption; Bone Density Conservation Agents; Magnetic Resonance Imaging; Walking; Ambulation; Locomotor; Locomotion; Treadmill; Spinal Cord Injury

Outcome Measures

Primary Outcomes (3)

• change in thigh muscle cross-sectional area

  change in thigh muscle cross-sectional area assessed via MRI

  baseline, 3 months, 6 months

• change in 6 min walk test (6MWT)

  change in distance covered on 6MWT

  baseline, 1 month, 3 months, 6 months

• change in distal femur bone mineral density

  change in distal femur bone mineral density (BMD) assessed via DEXA

  baseline, 3 months, 6 months

Secondary Outcomes (4)

• change in knee extensor peak torque

  baseline, 3 months, 6 months

• change in 10m walk test (10mWT)

  baseline, 1 month, 3 months, 6 months

• change in bone resorption marker

  baseline, 3 months, 6 months

• change in bone formation marker

  baseline, 3 months, 6 months

Study Arms (3)

testosterone enanthate

EXPERIMENTAL

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

Drug: Testosterone Enanthate

locomotor training, testosterone enanthate

EXPERIMENTAL

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

Drug: Testosterone Enanthate; Behavioral: Locomotor Training

non-interventional control

NO INTERVENTION

Non-interventional control group

Interventions

Testosterone Enanthate DRUG

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

Also known as: delatestryl

locomotor training, testosterone enanthate; testosterone enanthate

Locomotor Training BEHAVIORAL

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

Also known as: Treadmill training and overground walking

locomotor training, testosterone enanthate

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Participants must be male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men \>18 years of age
• Diagnosis of an incomplete SCI involving spinal segments L1 or above or a clinically complete SCI involving spinal segments T2-L1, with upper motor neuron injury signs (i.e., spasticity, hypertonicity) for \>60-days
• Low serum total testosterone (\<300 ng/dL), bioavailable testosterone (\<110 ng/dL), or free testosterone (\<46 pg/mL or \<4.6 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, definted as self-selected walking pace ≤1.0 m/s on a 10mWT, either with or without gait devices or braces and with or without assistance, or as self-selected walking pace \>1.0 m/s with reliance on a gait device or brace or with highly compensated movement impairments, as identified by a trained observer.
• 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

You may not qualify if:

• 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) 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)

Sponsors & Collaborators

• North Florida Foundation for Research and Education: lead
• North Florida/South Georgia Veterans Health System: collaborator
• Brooks Rehabilitation: collaborator
• University of Florida: collaborator
• VA Eastern Colorado Health Care System: collaborator

Study Sites (2)

North Florida/South Georgia Veterans Health System

Gainesville, Florida, 32608, United States

RECRUITING

Brooks Rehabilitation

Jacksonville, Florida, 32216, United States

RECRUITING

MeSH Terms

Conditions

Spinal Cord Injuries; Trauma, Nervous System; Wounds and Injuries; Central Nervous System Diseases; Spinal Cord Diseases; Gonadal Disorders; Endocrine System Diseases; Hypogonadism; Genital Diseases, Male; Mobility Limitation; Gait Disorders, Neurologic; Nervous System Diseases; Bone Resorption

Interventions

testosterone enanthate

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Bone Diseases; Musculoskeletal Diseases

Study Officials

• Joshua F Yarrow, PhD

  North Florida/South Georgia Veterans Health System

  STUDY DIRECTOR

• Dana M Otzel, Phd

  North Florida/South Georgia Veterans Health System

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joshua F Yarrow, PhD

CONTACT

(352) 548-6477; joshua.yarrow@va.gov

Dana M Otzel, PhD

CONTACT

(352) 548-6477; dana.otzel@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Health Scientist

Study Record Dates

• First Submitted: July 6, 2020
• First Posted: July 8, 2020
• Study Start: January 31, 2021
• Primary Completion: January 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: May 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be shared according to the requirements described by the Department of Veterans Affairs, Office of Research \& Development.
• Access Criteria: Data will be shared according to the requirements described by the Department of Veterans Affairs, Office of Research \& Development.

Locations

US (2)