Clinical trial NCT06853015: Double Dose 4-AP on Functional Recovery After Spinal Cord Injury
Official title: Effects of Twice-daily Dosing 4-AP on Functional Recovery After Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: SCI - Spinal Cord Injury
Keywords: spinal cord injury
neurostimulation
4-AP
rehabilitation
Lead sponsor: Shirley Ryan AbilityLab
Sponsor class: OTHER
First posted: 2025-02-28
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test a strategy to potentiate functional recovery of lower limb motor function in individuals with spinal cord injury (SCI). The FDA approved drug, Dalfampridine (4-AP). 4-AP will be used twice-daily in combination of Spike-timing-dependent plasticity (STDP) stimulation and STDP stimulation with limb training.

Detailed description: Currently, research has shown that 4-AP has a positive effect on sensory and motor function rehabilitation in humans with chronic SCI in addition to decreasing recorded spasticity, increased sensation, and decreased pain. A pharmacokinetic study showed that twice-daily administration of sustained release 4-AP maintains a steadier plasma concentration. Utilizing limb training to promote recovery of motor function is enhanced by eliciting STDP in the limbs. An important strength of this aim is the combination of training and STDP, which aims to enhance the beneficial effects of motor training by promoting plasticity in the corticospinal pathway. Training effects on physiological pathways will be explored and correlated with lower limb motor function. We hypothesize that introducing 4-AP into the STDP stimulation and STDP stimulation with training will further improve motor function rehabilitation in patients with chronic SCI.

Eligibility criteria: Inclusion Criteria:

* Male and females between ages 18-85 years
* SCI 6 months post injury
* Spinal Cord injury at or above L2
* ASIA A, B, C, or D, complete or incomplete
* The ability to perform a small visible contraction with dorsiflexion and hip flexor muscles

Exclusion Criteria:

* Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease
* Any history of renal impairment
* Any debilitating disease prior to the SCI that caused exercise intolerance
* Premorbid, ongoing major depression or psychosis, altered cognitive status
* History of head injury or stroke
* Vascular, traumatic, tumoral, infectious, or metabolic lesion of the brain, even without history of seizure, and without anticonvulsant medication
* History of seizures or epilepsy
* Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold (see appendix 2)
* Pregnant females
* If a women of child bearing age is unsure of the pregnancy, and does not want to take the pregnancy test
* Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal cord disease such as spinal stenosis, spina bifida, MS, or herniated disk
* Metal plate in skull
* Individuals with scalp shrapnel, cochlear implants, or aneurysm clips
* Individuals taking Bupropion, Dolutegravir, Lacosamide, Trilaciclib, or PR Interval prolonging drugs

Primary outcomes:
measure: Change in TMEPs
timeFrame: TMEPs measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
measure: Change in MVC
timeFrame: MVC measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
Secondary outcomes:
measure: Change in 10-meter walk test
timeFrame: 10-m walk measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
measure: Change in 6-minute walk test
timeFrame: 6-min walk measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
measure: Change in International Standards for Neurological Classification of Spinal Cord Injury exam
timeFrame: Scores measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
measure: Change in EPT
timeFrame: EPT will be measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
measure: Change in surveys on ambulation, basic mobility, bowel and bladder management difficulties
timeFrame: SCI-QOL measured at at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
measure: Change in morphological characterization of corticospinal and reticulospinal pathways in MRI
timeFrame: MRI measured at baseline, and at 12 weeks (post 40 sessions).
Other outcomes:
measure: Changes in spinal excitability
timeFrame: Changes in spinal excitability will be measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
Locations:
city: Chicago
country: United States
facility: Shirley Ryan Abilitylab
state: Illinois
Study officials:
affiliation: Shirley Ryan Ability Lab
name: Monica Perez, PT, PhD
role: PRINCIPAL_INVESTIGATOR
References: