An Exercise Intervention to Educe Neuropathic Pain and Brain Inflammation After Spinal Cord Injury
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Change in Hippocampal volume
研究概览
简要总结
Spinal Cord Injury (SCI) leads to alterations in brain structure and function by spinal nerve damage, secondary inflammatory responses, and by the consequences of living with paralysis and neuropathic pain. Physical inactivity due to lower body paralysis rapidly leads to loss of muscle, and risk of heart disease. The leading cause of death after a spinal cord injury is cardiovascular disease, and just a year after injury, those with SCI have a peak exercise capacity half that of the unfit general population.
The good news is that aerobic exercise reduces the risk of chronic metabolic and cardiorespiratory diseases, reduces inflammation and pain, and increases mood and quality of life. Exercise can also reduce brain inflammation, enhance endogenous analgesia, and increases the size of the hippocampus.
The issue is that muscle paralysis in SCI restricts the ability to achieve the levels of exercise that is necessary for broad analgesic, anti-inflammatory and neuroprotective benefits. Arm exercise can have some effects on heart and lung capacity, but the small muscle mass is insufficient to produce more than modest aerobic work. With functional electrical stimulation (FES), leg muscles that are paralyzed can be made to contract, thereby allowing more of the body to be exercised. The full rowing stroke is produced by both the (stimulated) legs and arms, increasing the active muscle mass and resulting in an aerobic work-out that is intensive enough to improve heart, lung, and - maybe - brain function.
In this clinical trial of sub-acute spinal cord injured subjects, the investigators will study how 12 weeks of FES-RT, in comparisons to 12 weeks of wait-list, changes pain, brain structure, endogenous opioid function and brain inflammation.
The investigators will measure changes using positron emission tomography and magnetic resonance imaging. The investigators hypothesize a decrease in pain interference, an increase in hippocampal volume, increased endogenous opioid transmission in the periaqueductal gray, and decreased hippocampus neuroinflammation.
详细描述
This clinical trial will utilize a randomized, controlled, crossover design. Participants will be randomized to (A) 12 weeks of FES-RT followed by 12 weeks of treatment as usual or (B) 12 weeks of treatment as usual followed by 12 weeks of FES-RT.
Randomization will be computer generated and the study statistician will keep the key to appropriately conceal allocation of treatment until after obtaining baseline measures.
Exercise Intervention:
FES-RT occurs in two distinct steps - an initial strength training step, followed by FES-RT. Those with SCI can require at least two weeks and up to six weeks of strength-training. For the strength training, electrodes are placed over motor points of the quadriceps and hamstrings and intensity of the stimulus is set at the level producing full knee flexion-extension. Training is performed until subjects can complete a flexion extension protocol for 30 min without rest. During this time, the first set of PET-MR data will be obtained.
Subsequently, the FES-RT commences.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Outcomes Assessor)
盲法说明
Study statistician is masked to intervention type
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •* SCI at or below neurological level C5 with American Spinal Injury Association grade A, B or C, within 3-24 months after injury.
排除标准
- •pregnancy
- •breast feeding
- •contraindications to MRI
- •contraindications to PET current or past history of:
- •major medical illness
- •major neurological illness other than SCI
- •major psychiatric illness
- •major kidney or liver problems
- •use of tobacco
- •use of recreational drugs
- •an abnormal physical exam (e.g., heart murmurs or peripheral edema).
- •unresponsive to FES stimulation
- •heart disease
- •physical limitations to FES-RT success
- •blood pressure>140/90 mmHg
- •significant arrhythmias
- •current use of cardioactive medications
- •current grade 2 or greater pressure injuries at relevant contact sites
- •peripheral nerve compressions or rotator cuff tears that limit the ability to row
- •history of bleeding disorder
研究组 & 干预措施
FES rowing
Exercise training sessions will be performed 3 times per week for 12 weeks. The initial training sessions will include 6 sets of FES-rowing for 5 min at 60% of VO2 peak with a work-to-rest ratio of 2:1. Participants unable to row continuously for 5 min will row for 2-4 min with 30-second breaks incorporated until they achieve sets totaling 30 min. The goal is for each volunteer to achieve an exercise intensity of 70-85% maintained for a continuous 30-40 min performed 3 times each week.
干预措施: Functional Electrical Stimulation rowing exercise (Other)
Wait list
During the 12-week treatment as usual program, subjects will not participate in FES-rowing.
结局指标
主要结局
Change in Hippocampal volume
时间窗: Change between baseline and after 12 week FES intervention, and after 12 week wait list
MRI derived measurement of hippocampus volume
Change in PROMIS Pain Interference questionnaire
时间窗: Change between baseline and after 12 week FES intervention, and after 12 week wait list
The Patient-Reported Outcomes Measurement Information System (PROMIS(r)) Pain Interference instrument measure the self-reported consequences of pain on relevant aspects of a person's life and may include the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Pain Interference also incorporates items probing sleep and enjoyment in life. The scale ranges from 6 to 30, with 30 being the highest pain interference.
Change in Hippocampus glial activation
时间窗: Change between baseline and after 12 week FES intervention, and after 12 week wait list
11C-PBR28 SUV uptake in the hippocampus
Change PAG opioid binding potential
时间窗: Change between baseline and after 12 week FES intervention, and after 12 week wait list
Non-displaceable opioid binding potential of the periaqueductal gray
次要结局
未报告次要终点
研究者
Nils Clas Linnman
Assistant Professor
Spaulding Rehabilitation Hospital