Effects of Twice-daily Dosing 4-AP on Functional Recovery After Spinal Cord Injury
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Change in TMEPs
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
4-AP(AM) + STDP stimulation + training + 4-AP(PM)
The effects of the functional recovery of the lower-limb muscles will be determined after 40 sessions of twice-daily-dosing 4-AP, STDP stimulation and training.
干预措施: Dalfampridine (Drug)
Placebo(AM) + STDP stimulation + training + Placebo(PM)
The effects of the functional recovery of the lower-limb muscles will be determined after 40 sessions of twice-daily-dosing Placebo, STDP stimulation and training.
干预措施: Placebo (Drug)
4-AP(AM) + STDP stimulation + training + 4-AP(PM)
The effects of the functional recovery of the lower-limb muscles will be determined after 40 sessions of twice-daily-dosing 4-AP, STDP stimulation and training.
干预措施: STDP stimulation (Other)
4-AP(AM) + STDP stimulation + training + 4-AP(PM)
The effects of the functional recovery of the lower-limb muscles will be determined after 40 sessions of twice-daily-dosing 4-AP, STDP stimulation and training.
干预措施: Exercise training (Behavioral)
Placebo(AM) + STDP stimulation + training + Placebo(PM)
The effects of the functional recovery of the lower-limb muscles will be determined after 40 sessions of twice-daily-dosing Placebo, STDP stimulation and training.
干预措施: STDP stimulation (Other)
Placebo(AM) + STDP stimulation + training + Placebo(PM)
The effects of the functional recovery of the lower-limb muscles will be determined after 40 sessions of twice-daily-dosing Placebo, STDP stimulation and training.
干预措施: Exercise training (Behavioral)
结局指标
主要结局
Change in TMEPs
时间窗: TMEPs measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
Electrical stimulation will be performed placing the cathode on the upper thoracic between the spinal processes between T3 and T4 vertebrae and the anode at \~10 cm above
Change in MVC
时间窗: MVC measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
Individuals will perform a maximum voluntary contraction (MVC) of each targeted muscle (quadriceps femoris, tibialis anterior or soleus) through surface electrodes secured to the skin over the belly of each muscle. Ankle flexion torque will be measured by measured by force sensors.
次要结局
- Change in 10-meter walk test(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(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(Scores measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).)
- Change in EPT(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(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(MRI measured at baseline, and at 12 weeks (post 40 sessions).)
研究者
Monica Perez
Scientific Chair
Shirley Ryan AbilityLab