Double Dose 4-AP on Functional Recovery After Spinal Cord Injury

Официальное название

Effects of Twice-daily Dosing 4-AP on Functional Recovery After Spinal Cord Injury

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Dalfampridine
  The study drug (4-AP) will be administered as a 10 mg dose twice a day.
• Препарат Placebo
  The placebo provided by the SRAL pharmacy that looks identical to the 4-AP, will be administered twice a day.
• Другое STDP stimulation
  Paired stimulation will be given to the spinal cord and to peripheral nerves so that the signals are received at the spinal cord at a specific interval.
• Поведенческое Exercise training
  Lower-limb exercises will involve over-ground walking, treadmill, walking and stair climbing training.

Первичные конечные точки

• Change in TMEPs [Срок оценки: TMEPs measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).]
• Change in MVC [Срок оценки: MVC measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).]

Вторичные конечные точки (6)

• Change in 10-meter walk test [Срок оценки: 10-m walk measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).]
• Change in 6-minute walk test [Срок оценки: 6-min walk measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).]
• Change in International Standards for Neurological Classification of Spinal Cord Injury exam [Срок оценки: Scores measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).]
• Change in EPT [Срок оценки: EPT will be measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).]
• Change in surveys on ambulation, basic mobility, bowel and bladder management difficulties [Срок оценки: SCI-QOL measured at at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).]
• Change in morphological characterization of corticospinal and reticulospinal pathways in MRI [Срок оценки: MRI measured at baseline, and at 12 weeks (post 40 sessions).]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Shirley Ryan Abilitylab — Chicago

Идентификаторы

NCT: NCT06853015 · STU00221545

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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