Testosterone and Long Pulse Stimulation After SCI

NCT03345576 | Completed Phase 2 Results DMC FDA Drug FDA Device

• 1 other identifier: B2649-R
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Denervation following spinal cord injury (SCI) limits beneficial application of neuromuscular electrical stimulation (NMES). SCI with denervation results in extensive muscle atrophy that is accompanied with several cardio-metabolic health risks. The current proposal provides a novel intervention by examining the effects of long pulse width stimulation (LPWS) and testosterone replacement therapy (TRT) on restoring muscle size and leg lean mass after denervation in persons with SCI. This intervention will be rewarding for Veterans and Civilians with SCI who do not benefit from exercising their lower extremity muscles because denervation has limited the response to standard surface NMES. The investigators will study the biochemical mechanisms that contribute to changes in muscle size following this novel training. Combing both pharmaceutical and physical-therapeutic interventions will optimize restoration of muscle size after SCI.

Conditions

Spinal Cord Injury

Keywords

Electric Stimulation; Spinal Cord Injuries; Muscle Denervation; carbohydrate metabolism; Lipids metabolism; Basal Metabolic Rate; Muscle Proteins; Mitochondria, Muscle; RNA; Rehabilitation

Outcome Measures

Primary Outcomes (1)

• Muscle Size Change

  Magnetic resonance imaging (MRI): The skeletal muscle area will be measured at baseline 6 months and 12 months after training (post-intervention).

  Baseline, 6 months and 12 months

Secondary Outcomes (2)

• Basal Metabolic Rate

  Baseline, 6 months and 12 months

• Mitochondrial Complex Activities

  Mitochondrial measurements were conducted over 1 year period at baseline [BL, before starting any intervention], Post-intervention 1 [ P1; 6 months after starting interventions] and Post-intervention 2 [P2-12 months after starting interventions]

Study Arms (2)

Testosterone and LPWS

EXPERIMENTAL

Twelve patients will undergo 1 year of supervised training examining the effects of testosterone replacement therapy (TRT) and long pulse width stimulation (LPWS) in persons with denervated spinal cord injury.

Device: Testosterone and LPWS

Testosterone and standard NMES

SHAM COMPARATOR

Twelve patients will undergo 1 year of supervised training examining the effects of testosterone replacement therapy (TRT) and standard surface neuromuscular electrical stimulation (NMES) in persons with denervated spinal cord injury.

Drug: Testosterone and standard NMES

Interventions

Testosterone and LPWS DEVICE

Twelve patients will undergo 1 year of supervised training examining the effects of testosterone replacement therapy (TRT) and long pulse width stimulation (LPWS) in persons with denervated spinal cord injury.

Also known as: Testosterone and long pulse width stimulation

Testosterone and LPWS

Testosterone and standard NMES DRUG

Twelve patients will undergo 1 year of supervised training examining the effects of testosterone replacement therapy (TRT) and standard surface neuromuscular electrical stimulation (NMES) in persons with denervated spinal cord injury.

Also known as: Testosterone and neuromuscular electrical stimulation

Testosterone and standard NMES

Eligibility Criteria

• Age: 18 Years - 70 Years
• Gender Eligibility Details: Only men with SCI, women will not be included in the current study because administering testosterone replacement therapy (TRT) is neither appropriate nor safe.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Traumatic motor complete SCI and level of injury of T10 and below
• Only participants with lower motor neuron (LMN) denervation as determined by EMG testing
• Participants must also have an absence of reflexes, denervation of both knee extensor muscles
• Tolerance to LPWS paradigm
• Both knee extensors will also have to be unresponsive (i.e., no observed tetanic contraction or twitches) to standard electrical stimulation procedures (stimulation frequency: 30 Hz; pulse duration:450 s and amplitude of the current:200 mA)
• All participants will undergo International Standards for Neurological Classification of SCI (ISNCSCI) examination for neurological level and function and only those with American Spinal Injury Classification (AIS A and B; i.e. motor deficit below the level of injury)

You may not qualify if:

• Diagnosis of neurological injury other than SCI
• Pre-existing medical conditions will be excluded (cardiovascular disease, uncontrolled type II DM and those on insulin requirements) or other concurrent medical conditions judged to be contraindicated by the site physician.
• Hematocrit above 50% and severe urinary tract infection or symptoms
• Those with hyper-physiological testosterone level above 800 ng/dl
• Those who will fail to tolerate the LPWS paradigm
• Progressive condition that would be expected to result in changing neurological status
• Lower extremity fracture around the knee joint (distal femur or proximal tibia) within the last 2 years from enrollment in the study
• Knee BMD \< 0.60 gm/cm2
• Total hip BMD T-scores \< -3.5
• Untreatable severe spasticity judged to be contraindicated by the site Physician
• Untreated or uncontrolled hypertension (systolic blood pressure \>140 mmHg; diastolic blood pressure \>90 mmHg)
• Pressure ulcer of the trunk, pelvic area, or lower extremities of grade 3 or more
• Psychopathology documentation in the medical record or history that may conflict with study objectives

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Hunter Holmes McGuire VA Medical Center: collaborator

Study Sites (1)

Hunter Holmes McGuire VA Medical Center, Richmond, VA

Richmond, Virginia, 23249-0001, United States

Location

Related Publications (2)

• Gorgey AS, Khalil RE, Alrubaye M, Gill R, Rivers J, Goetz LL, Cifu DX, Castillo T, Caruso D, Lavis TD, Lesnefsky EJ, Cardozo CC, Adler RA. Testosterone and long pulse width stimulation (TLPS) for denervated muscles after spinal cord injury: a study protocol of randomised clinical trial. BMJ Open. 2022 Oct 5;12(10):e064748. doi: 10.1136/bmjopen-2022-064748.

  PMID: 36198461 BACKGROUND

• Alazzam AM, Goldsmith JA, Khalil RE, Khan MR, Gorgey AS. Denervation impacts muscle quality and knee bone mineral density after spinal cord injury. Spinal Cord. 2023 Apr;61(4):276-284. doi: 10.1038/s41393-023-00885-3. Epub 2023 Mar 10.

  PMID: 36899099 RESULT

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

Testosterone

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Ashraf S. Gorgey
• Organization: Richmond VAMC

ashraf.gorgey@va.ogv

8046755000

Study Officials

• Ashraf Gorgey, PhD PT

  Hunter Holmes McGuire VA Medical Center, Richmond, VA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participant will be masked to the type of electrical stimulation (LPWS vs. standard NMES)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2017
• First Posted: November 17, 2017
• Study Start: July 1, 2018
• Primary Completion: June 30, 2023
• Study Completion: November 30, 2023
• Last Updated: October 14, 2025
• Results First Posted: December 11, 2024

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Throughout the study and at the completion of the study.

Locations

US (1)