Transformation of Paraplegic Paralysis to Overground Stepping in Humans
试验速览
- 阶段
- 早期 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Lower Extremity Electromyography, change over time
研究概览
简要总结
The main goal of the project is to develop multiple noninvasive neuromodulatory strategies to facilitate full weight bearing stepping overground in people with paralysis. We will determine the effectiveness of combining noninvasive spinal cord stimulation and the administration of buspirone (a monoaminergic agonist) in facilitating locomotor activity in a gravity-neutral apparatus, during body weight supported stepping on a treadmill, when stepping overground, or during full weight bearing stepping overground in a rolling walker. Our objective is to identify the experimental variables that define the efficacy of these novel neuromodulatory techniques over a 5 year period in 15 participants with severe spinal cord injury who are at least one year post-injury.
详细描述
Aim 1: Define the relative effectiveness of transcutaneous electrical stimulation at multiple stimulation spinal sites and oral Buspirone in facilitating nonweight-bearing (gravity neutral device, GND) and weight-bearing (treadmill) stepping in individuals with chronic motor complete paralysis.
Aim 1.1: Define the relative effectiveness of transcutaneous electrical stimulation at multiple spinal sites to facilitate non-weight-bearing (GND) and weight-bearing (treadmill) stepping in spinal cord injury subjects.
Aim 1.2: Define the relative effectiveness of transcutaneous electrical stimulation at multiple spinal sites plus oral Buspirone to facilitate nonweight-bearing (gravity neutral device, GND) and weight-bearing (treadmill) stepping in spinal cord injury subjects.
Aim 2: Determine the relative effectiveness of overground LT combined with transcutaneous electrical stimulation and/or oral Buspirone in lowering the robotic assistance and enhancing the ability to step self-assisted in a rolling walker during over-ground stepping in individuals with a chronic, severe (AIS A/B) spinal injury.
Aim 3: Determine the relative effectiveness of overground LT combined with transcutaneous electrical stimulation and/or oral Buspirone in lowering the robotic assistance and enhancing the ability to step self-assisted in a rolling walker during over-ground stepping in individuals with motor incomplete (AIS C) paralysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Due to the objectives of the study, the identity of test and control treatments will not be known to investigators, research staff, or participants during the Treatment Phase. The following study procedures will be in place to ensure double-blind administration of study treatments. Access to the randomization code will be strictly controlled.
- Packaging and labeling of test and control treatments will be identical to maintain the blind.
- The study blind will be broken on completion of the clinical study and after the study database has been locked.
BuSpar (buspirone) and matching placebo tablets (2x/day) will be obtained and dispensed by the investigational pharmacy.
Study drug and placebo will be labeled with the required FDA warning statement, the protocol number, a treatment number, the name of the sponsors, and directions for patient use and storage.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •by study group:
- •Participants with Motor Complete SCI:
- •18-65 years old,
- •Stable medical condition,
- •At least 1-year post-injury,
- •Non-progressive SCI,
- •Motor complete paraplegia: Unable to voluntarily move any joint of the lower limbs,
- •Inability to walk independently due to SCI,
- •Presence of active spinally evoked responses over the lumbo-sacral spinal cord using spinal Cord Transcutaneous Stimulation (scTS).
- •Participants with Motor Incomplete SCI:
- •18-65 years old,
- •Stable medical condition,
- •At least 1-year post-injury,
- •Non-progressive SCI,
- •Motor incomplete paraplegia: Able to voluntarily move at least 1 joint of the lower limbs bilaterally,
- •Inability to walk independently in the community due to SCI,
- •Presence of active spinally evoked responses over the lumbo-sacral spinal cord using scTS.
排除标准
- •Untreated pressure sores,
- •Unhealed bone fractures,
- •Untreated active urinary tract infections,
- •Peripheral lower limb neuropathies unrelated to SCI,
- •Seizure disorders,
- •Cardiopulmonary disease unrelated to SCI,
- •Untreated anemia,
- •Ventilator dependency,
- •Female participants: Pregnant or planning to become pregnant during the time course of study, or nursing,
- •Healing wounds/surgical sites along the spine, levels T9-L5,
- •Anti-spasticity implantable pumps,
- •Untreated clinically significant depression, psychiatric disorders, or ongoing drug abuse,
- •Colostomy bag, urostomy,
- •Individuals with abnormal blood panel results related to hepatic function, Individuals with abnormal estimated glomerular filtration rate (eGFR) and increase Creatinine Clearance (CrCl) levels above the normal range,
- •Individuals unwilling or unable to wean from drug(s) that interact(s) with buspirone, such as: Monoamine oxidase inhibitors (MAOIs) - Selegiline (Emsam), Isocarboxazid (Marplan), Phenelzein (Nardil), and Tranylcypromine (Parnate).
研究组 & 干预措施
Complete Spinal Cord Injury - Gravity Neutral Stepping
Group 1 will begin with a 3-4-month preparation phase and up to 12 sessions in the gravity neutral device (GND) will occur. The training sessions in the GND will be used to obtain the optimal stimulation parameters. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours. This will be done in the GND in the presence of stimulation. Afterwards, Intervention 2 will include the same training procedures with the addition of Buspirone or Placebo in a cross-over fashion halfway through this phase.
干预措施: Buspirone (Drug)
Complete Spinal Cord Injury - Gravity Neutral Stepping
Group 1 will begin with a 3-4-month preparation phase and up to 12 sessions in the gravity neutral device (GND) will occur. The training sessions in the GND will be used to obtain the optimal stimulation parameters. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours. This will be done in the GND in the presence of stimulation. Afterwards, Intervention 2 will include the same training procedures with the addition of Buspirone or Placebo in a cross-over fashion halfway through this phase.
干预措施: Non-invasive Spinal Cord Stimulation (Device)
Complete Spinal Cord Injury - Gravity Neutral Stepping
Group 1 will begin with a 3-4-month preparation phase and up to 12 sessions in the gravity neutral device (GND) will occur. The training sessions in the GND will be used to obtain the optimal stimulation parameters. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours. This will be done in the GND in the presence of stimulation. Afterwards, Intervention 2 will include the same training procedures with the addition of Buspirone or Placebo in a cross-over fashion halfway through this phase.
干预措施: Gravity Neutral Device (Device)
Complete Spinal Cord Injury - Gravity Neutral Stepping
Group 1 will begin with a 3-4-month preparation phase and up to 12 sessions in the gravity neutral device (GND) will occur. The training sessions in the GND will be used to obtain the optimal stimulation parameters. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours. This will be done in the GND in the presence of stimulation. Afterwards, Intervention 2 will include the same training procedures with the addition of Buspirone or Placebo in a cross-over fashion halfway through this phase.
干预措施: Body Weight Supported Treadmill Training (Device)
Incomplete Spinal Cord Injury - Overground Stepping
Group 3 will begin with a 3-month preparation phase and up to 12 sessions stepping overground. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours. The overground session will use the rolling walker in the presence of stimulation. Afterwards, the second phase will include the same training procedures with the addition of Buspirone/placebo.
干预措施: Buspirone (Drug)
Incomplete Spinal Cord Injury - Overground Stepping
Group 3 will begin with a 3-month preparation phase and up to 12 sessions stepping overground. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours. The overground session will use the rolling walker in the presence of stimulation. Afterwards, the second phase will include the same training procedures with the addition of Buspirone/placebo.
干预措施: Non-invasive Spinal Cord Stimulation (Device)
Incomplete Spinal Cord Injury - Overground Stepping
Group 3 will begin with a 3-month preparation phase and up to 12 sessions stepping overground. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours. The overground session will use the rolling walker in the presence of stimulation. Afterwards, the second phase will include the same training procedures with the addition of Buspirone/placebo.
干预措施: Rolling Walker (Device)
Incomplete Spinal Cord Injury - Overground Stepping
Group 3 will begin with a 3-month preparation phase and up to 12 sessions stepping overground. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours. The overground session will use the rolling walker in the presence of stimulation. Afterwards, the second phase will include the same training procedures with the addition of Buspirone/placebo.
干预措施: Overground stepping (Device)
Complete Spinal Cord Injury - Overground Stepping
Group 2 will begin with a 3-month preparation phase and up to 12 sessions of overground stepping. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours overground training, in the presence of stimulation and Buspirone/placebo. The second phase will include the same training procedures except for the removal of Buspirone/placebo administration. The third phase will include sessions twice per week of the overground with stimulation and one day per week using a rolling walker with stimulation. The last phase will include 2 sessions per week using the rolling walker in the presence of stimulation and Buspirone/placebo.
干预措施: Buspirone (Drug)
Complete Spinal Cord Injury - Overground Stepping
Group 2 will begin with a 3-month preparation phase and up to 12 sessions of overground stepping. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours overground training, in the presence of stimulation and Buspirone/placebo. The second phase will include the same training procedures except for the removal of Buspirone/placebo administration. The third phase will include sessions twice per week of the overground with stimulation and one day per week using a rolling walker with stimulation. The last phase will include 2 sessions per week using the rolling walker in the presence of stimulation and Buspirone/placebo.
干预措施: Non-invasive Spinal Cord Stimulation (Device)
Complete Spinal Cord Injury - Overground Stepping
Group 2 will begin with a 3-month preparation phase and up to 12 sessions of overground stepping. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours overground training, in the presence of stimulation and Buspirone/placebo. The second phase will include the same training procedures except for the removal of Buspirone/placebo administration. The third phase will include sessions twice per week of the overground with stimulation and one day per week using a rolling walker with stimulation. The last phase will include 2 sessions per week using the rolling walker in the presence of stimulation and Buspirone/placebo.
干预措施: Overground stepping (Device)
Complete Spinal Cord Injury - Overground Stepping
Group 2 will begin with a 3-month preparation phase and up to 12 sessions of overground stepping. Next, participants will enter Intervention Phase 1 where they will receive training sessions 3 days/week for approximately 2 hours overground training, in the presence of stimulation and Buspirone/placebo. The second phase will include the same training procedures except for the removal of Buspirone/placebo administration. The third phase will include sessions twice per week of the overground with stimulation and one day per week using a rolling walker with stimulation. The last phase will include 2 sessions per week using the rolling walker in the presence of stimulation and Buspirone/placebo.
干预措施: Rolling Walker (Device)
结局指标
主要结局
Lower Extremity Electromyography, change over time
时间窗: Before and after each study phase, 1 year per group.
Assessment of muscle activity, measured by electromyography, while the leg is suspended in a gravity neutral position.
Lower Extremity Kinematics, change over time
时间窗: Before and after each study phase, 1 year per group.
Assessment of low extremity 3D position, measured by motion analysis system, while the leg is suspended in a gravity neutral position.
Treadmill Electromyography Assessment, change over time
时间窗: Before and after each study phase, 1 year per group.
Muscle activity, measured by electromyography, will be recorded during weight supported stepping on a treadmill.
Spinal Pathway Electrophysiology, change over time
时间窗: Before and after each study phase, 1 year per group.
Evoked potentials in the lower extremities will recorded in response to nerve or spinal stimulation.
Voluntary Lower Extremity Angles, change over time
时间窗: Before and after each study phase, 1 year per group.
Assessments of knee, ankle, and toe movements will be performed by measuring angles produced during flexion and extension. The same units of measure will be used for each part of the leg.
Voluntary Lower Extremity Forces, change over time
时间窗: Before and after each study phase, 1 year per group.
Assessments of knee, ankle, and toe forces during movements will be performed by measuring forces produced during flexion and extension. The same units of measure will be used for each part of the leg.
Body Temperature, change over time
时间窗: Before and after each study phase, 1 year per group.
We will measure body temperature using standard methods to assess values at rest and during exercise.
Blood Pressure, change over time
时间窗: Before and after each study phase, 1 year per group.
We will measure blood pressure (systolic and diastolic) using standard methods to assess values at rest and during exercise.
Heart Rate, change over time
时间窗: Before and after each study phase, 1 year per group.
We will measure the heart rate using standard electrocardiography to assess values at rest and during exercise.
Respiration Rate, change over time
时间窗: Before and after each study phase, 1 year per group.
We will measure respiratory rate using standard methods to assess values at rest and during exercise.
Dual-energy X-ray absorptiometry, change over time
时间窗: Before and after each study phase, 1 year per group.
We will use dual-energy X-ray absorptiometry to measure bone and soft tissue density.
Acoustic Gastro-Intestinal Surveillance, change over time
时间窗: Before and after each study phase, 1 year per group.
We will use non-invasive sensors placed on the abdomen to detect signals related to the digestive state.
Bladder capacity, change over time
时间窗: Before and after each study phase, 1 year per group.
We will use a standard technique to measure bladder volume change during voiding.
Urodynamics, change over time
时间窗: Before and after each study phase, 1 year per group.
We will use a standard technique to measure the abdominal pressure change during voiding.
Cognitive interference, change over time
时间窗: Before and after each study phase, 1 year per group.
A cognitive assessment using Stroop test will be administered to assess cognitive function during stress.
Assessment of verbal fluency, change over time
时间窗: Before and after each study phase, 1 year per group.
Controlled Oral Word Association Test (COWAT) will be administered to assess verbal fluency that measures ability of spontaneous production of words.
次要结局
- International Standards of Neurological Classification of Spinal Cord Injury, change over time(Before and after each study phase, 1 year per group.)
- Spinal Cord Injury Functional Ambulation Inventory, change over time(Before and after each study phase, 1 year per group.)
- Spinal Cord Independence Measure III, change over time(Before and after each study phase, 1 year per group.)
- Walking Index for Spinal Cord Injury-II, change over time(Before and after each study phase, 1 year per group.)
- Ashworth Scale, change over time(Before and after each study phase, 1 year per group.)
研究者
Alexander V Ovechkin, MD, PhD
Professor
University of Louisville