Investigating drugs to improve motor responses in chronic spinal cord injury

The Role of Pharmacological Agents in Restoring Neuronal Excitability After Chronic Spinal Cord Injury (SCI)

This study is testing if three approved medications can help improve movement in people with chronic spinal cord injuries when combined with hand training exercises.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Bronx VA Medical Center (Federal)
• Locations: 1 site (Bronx, New York)
• Trial ID: NCT05708274 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the short-term effects of three FDA-approved drugs—cyproheptadine, carbidopa-levodopa, and atomoxetine—on motor responses when combined with hand training exercises in individuals with chronic spinal cord injury. Participants will undergo a double-blind, placebo-controlled, randomized crossover design, where they will receive each drug or placebo in a randomized order across four visits. The study will measure various aspects of nerve transmission and muscle response using noninvasive techniques, including electromyography and transcranial magnetic stimulation. A total of 28 participants will be enrolled over a two-year period at the James J. Peters VA Medical Center in Bronx, NY.

Who should consider this trial

Good fit: Ideal candidates are males and females aged 18 to 65 with clinically stable chronic spinal cord injuries at or above the C8 spinal segment.

Not a fit: Patients with complete spinal cord injuries or those unable to meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance motor function and rehabilitation outcomes for patients with chronic spinal cord injuries.

How similar studies have performed: While the combination of these specific drugs with hand training is novel, similar approaches have shown promise in enhancing motor function in related conditions.

Eligibility criteria

Inclusion Criteria:

* Male or female between 18 and 65 years of age; clinically stable chronic (\> 12 months) SCI at or above C8 spinal segment;
* Motor-incomplete with a score of 2 or more (out of 5) on manual muscle testing (MMT) of finger extension, finger flexion, or finger abduction in left or right hand(s); or able to perform thumb-index finger pinch of the left or right hand;
* Detectable stimulation-evoked muscle responses of the left or right first dorsal interosseous (FDI) and/or abductor pollicis brevis (APB); Detectable FDI/APB surface electromyography (EMG) muscle activity during thumb-index finger pinch;
* Must have stable: medication \[≥ 30 days prior\]; rehabilitation regimen \[≥ 15 days prior\];
* Must be able to: abstain from alcohol, smoking and caffeine consumption on the day prior/of each experiment; abstain from recreational drugs for the entirety of the study; commit to study requirements (i.e., 7 visits); provide informed consent.

Exclusion Criteria:

* History of moderate or severe head trauma (loss of consciousness for greater than one hour or evidence of brain contusion or hemorrhage or depressed skull fracture on prior imaging);
* History of other serious central or peripheral neurological injury;
* History of implanted brain/spine/nerve stimulators, aneurysm clips, ferromagnetic metallic implants in the head (except inside mouth); cochlear implants; cardiac pacemaker/defibrillator; intracardiac lines; currently increased intracranial pressure; or other contraindications to brain stimulation or task performance;
* Ventilator dependence or patent tracheostomy site;
* Unstable syrinx, or multiple spinal cord lesions;
* Unclear diagnosis; History of stroke, brain tumor, brain abscess, or multiple sclerosis;
* Personal history of seizures; extensive family history of seizures; use of medications that lower seizure threshold (e.g., amphetamines, dalfampridine, and bupropion);
* Use of the study medications; Use of medications known to have significant adverse interactions with the study medication as described in the manufacturers' prescribing information \[14 days prior\]; previous allergic reaction or hypersensitivity to study drug(s);
* Presence of a medical condition that represents a risk for study drug(s) administration; evidence of liver disease or clinical jaundice; neutropenia; glaucoma; gastrointestinal ulcer(s); active malignancy; undiagnosed skin lesions; autoimmune disorders; chronic infectious diseases (e.g. HIV, hepatitis B or C); pregnancy or nursing mothers (a pregnancy urine test may be warranted); neurologic disorders (including a history of serious head trauma or seizures), and uncontrolled cardiovascular, metabolic, pulmonary or renal disease; premorbid, ongoing major depression or psychosis, altered cognitive status; bipolar disorder; suicidal ideation or past suicide attempts;
* History of severe hearing problems, loss or tinnitus;
* Presence of urinary infection, fever, pressure ulcer; or open skin lesions (shoulders or arms);
* Recent history (\< 6 months) of recurrent autonomic dysreflexia, defined as a syndrome of sudden rise in systolic pressure greater than 20 mm Hg or diastolic pressure greater than 10 mm Hg, without rise in HR, accompanied by symptoms such as headache, facial flushing, sweating, nasal congestion, and blurry vision (closely monitored during all testing procedures);
* Heavy alcohol consumption (greater than equivalent of 5 oz of liquor) within previous 48 hours;
* Recent history (\>1 year) of chemical substance dependency or significant psychosocial disturbance;
* Study participation of an investigational drug or device \[60 days prior\];
* Unsuitable for study participation as determined by the study physician.

Where this trial is running

Bronx, New York

• James J. Peters Veterans Affairs Medical Center — Bronx, New York, United States (Recruiting)

Study contacts

• Principal investigator: Lynda M Murray, PhD — Bronx VA Medical Center / James J. Peters Veterans Affairs Medical Center
• Study coordinator: Caitlyn "Sig" N Sigafose, BS

Conditions Spinal Cord Injuries; Transcranial magnetic stimulation; Pharmacological agents; Transcutaneous spinal cord stimulation; Hand exercise