Effects of 4-AP on Functional Recovery After Spinal Cord Injury
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 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 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. 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 at enhancing the beneficial effects of motor training by promoting plasticity in the corticospinal pathway. We hypothesize that introducing 4-AP into the STDP stimulation and STDP stimulation with lower-limb 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
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
Participants will not know if they receive 4-AP or placebo over the course of the study and the investigators are also blinded except for PI (Dr. Monica Perez).
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 at least 4 weeks post injury
- •Spinal Cord injury at or above L2
- •ASIA A,B,C, or D, complete or incomplete
- •Possess the following abilities
- •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
Placebo+STDP+training
The effects of the functional recovery of the lower-limb muscles will be determined after 10 sessions of placebo drug, STDP stimulation and training.
干预措施: STDP stimulation (Other)
Placebo+STDP+training
The effects of the functional recovery of the lower-limb muscles will be determined after 10 sessions of placebo drug, STDP stimulation and training.
干预措施: Exercise training (Behavioral)
Dalfampridine (4-AP)+STDP+training for extended sessions
The long-term effects of the functional recovery of the lower-limb muscles will be determined after 40 sessions of 4-AP, STDP stimulation and training.
干预措施: STDP stimulation (Other)
Dalfampridine (4-AP)+STDP+training
The effects of the functional recovery of the lower-limb muscles will be determined after 10 sessions of 4-AP, STDP stimulation and training.
干预措施: Exercise training (Behavioral)
Dalfampridine (4-AP)+STDP+training
The effects of the functional recovery of the lower-limb muscles will be determined after 10 sessions of 4-AP, STDP stimulation and training.
干预措施: STDP stimulation (Other)
Placebo+STDP+training
The effects of the functional recovery of the lower-limb muscles will be determined after 10 sessions of placebo drug, STDP stimulation and training.
干预措施: Placebo drug (Other)
Dalfampridine (4-AP)+STDP+training for extended sessions
The long-term effects of the functional recovery of the lower-limb muscles will be determined after 40 sessions of 4-AP, STDP stimulation and training.
干预措施: Exercise training (Behavioral)
Dalfampridine (4-AP)+STDP+training
The effects of the functional recovery of the lower-limb muscles will be determined after 10 sessions of 4-AP, STDP stimulation and training.
干预措施: Dalfampridine (Drug)
Dalfampridine (4-AP)+STDP+training for extended sessions
The long-term effects of the functional recovery of the lower-limb muscles will be determined after 40 sessions of 4-AP, STDP stimulation and training.
干预措施: Dalfampridine (Drug)
结局指标
主要结局
Change in TMEPs
时间窗: TMEPs measured at baseline and 3 weeks (10 sessions) for Dalfampridine+STDP+training and Placebo+STDP+training groups. TMEPs measured at baseline, 6 weeks (20 sessions), and 12 weeks (40 sessions) for extended sessions group.
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 and 3 weeks (10 sessions) for Dalfampridine+STDP+training and Placebo+STDP+training groups. MVC measured at baseline, 6 weeks (20 sessions), and 12 weeks (40 sessions) for extended sessions group.
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.
次要结局
- Change in 6-minute walk test(6-min walk measured at baseline and 3 weeks (10 sessions) for Dalfampridine+STDP+training & Placebo+STDP+training groups. 6-min walk measured at baseline, 6 weeks (20 sessions), and 12 weeks (40 sessions) for extended sessions group.)
- Change in MEPs(MEPs measured at baseline and 3 weeks (10 sessions) for Dalfampridine+STDP+training and Placebo+STDP+training groups. MEPs measured at baseline, 6 weeks (20 sessions), and 12 weeks (40 sessions) for extended sessions group.)
- Change in 10-meter walk test(10-m walk measured at baseline and 3 weeks (10 sessions) for Dalfampridine+STDP+training and Placebo+STDP+training groups. 10-m walk measured at baseline, 6 weeks (20 sessions), and 12 weeks (40 sessions) for extended sessions group.)
- Change in International Standards for Neurological Classification of Spinal Cord Injury exam(Scores measured at baseline and 3 weeks (10 sessions) for Dalfampridine+STDP+training and Placebo+STDP+training groups. Scores measured at baseline, 6 weeks (20 sessions), and 12 weeks (40 sessions) for extended sessions group.)
- Change in surveys on ambulation, basic mobility, bowel and bladder management difficulties(SCI-QOL measured at baseline and 3 weeks (10 sessions) for Dalfampridine+STDP+training & Placebo+STDP+training groups. SCI-QOL measured at baseline, 6 weeks (20 sessions), and 12 weeks (40 sessions) for extended sessions group.)
- Change in morphological characterization of corticospinal and reticulospinal pathways in MRI(MRI measured at baseline and 12 weeks (40 sessions) for Dalfampridine+STDP+training for extended sessions group.)
研究者
Monica Perez
Chair, Arms and Hands
Shirley Ryan AbilityLab