A Selective Adenosine 2a Antagonist to Enhance Training-related Gains in Walking Function for Persons With Chronic, Incomplete Spinal Cord Injury
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Walking Speed Post-Treatment 3
研究概览
简要总结
Breathing brief, moderate bouts of low oxygen trigger (low oxygen therapy, LOT) spinal plasticity (the ability of the nervous system to strengthen neural pathways based on new experiences), and improve walking after spinal cord injury (SCI). The greatest improvements in walking ability occur when LOT is administered prior to skill-based walking practice (WALK). However, the enduring benefits of LOT on walking recovery may be undermined by the accumulation of LOT-induced increase in extracellular adenosine. The goal of the study is to understand the extent to which istradefylline (adenosine 2a receptor antagonist) may limit the competing mechanisms of adenosine on LOT-induced walking recovery following SCI.
详细描述
This randomized, placebo-controlled clinical trial will examine the efficacy of a selective adenosine 2a antagonist (istradefylline) to enhance the beneficial effects of LOT-related gains on overground walking performance after spinal cord injury (SCI).
Participants will be randomly assigned to a combinatorial intervention: istradefylline+LOT, placebo+LOT, istradefylline+SHAM. Participants will be asked to avoid caffeine-containing substances for 48 hrs (> 5* half-life of ~7 hrs) before the start of the study. They also will refrain from consuming caffeine during the 4-week combinatorial intervention.
Participants enrolled in istradefylline+AIH will receive 20mg of istradefylline orally for 28 consecutive days. After 14 days of istradefylline treatment, the participants will receive 2 weeks (4 sessions/week) of LOT prior to 45min of skill-based walking practice (WALK) within the INSPIRE Lab. A single session of LOT will consist of 15 episodes of breathing 90s low levels of oxygen (10% O2) with 60s intervals at room air (21% O2).
Participants enrolled in istradefylline+SHAM will receive 20mg of istradefylline orally for 28 consecutive days. After 14 days of istradefylline treatment, the participants will receive 2 weeks (4 sessions/week) of SHAM therapy prior to 45min of skill-based walking practice (WALK) within the INSPIRE Lab. A single session of SHAM therapy will consist of 15 episodes of breathing 90s of normal levels of oxygen (21% O2) with 60s intervals at room air (21% O2).
Participants enrolled in placebo+AIH will receive 20mg of placebo (dextrose) treatment orally for 28 consecutive days. After 14 days of placebo treatment, the participants will receive 2 weeks (4 sessions/week) of LOT prior to 45min of skill-based walking practice (WALK) within the INSPIRE Lab. A single session of LOT will consist of 15 episodes of breathing 90s low levels of oxygen (10% O2) with 60s intervals at room air (21% O2).
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)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age 18 and 75 years (the latter to reduce the likelihood of heart disease) medical clearance to participate
- •lesion at or below C2 and above T12 with non-progressive etiology
- •classified as motor-incomplete with visible volitional leg movement
- •injury greater than 12 months
- •ability to advance one step overground without human assistance
排除标准
- •Concurrent severe medical illness (i.e., infection, cardiovascular disease, ossification, recurrent autonomic dysreflexia, unhealed decubiti, and history of pulmonary complications)
- •Pregnant women because of the unknown effects of AIH on pregnant women and fetus
- •History of seizures, brain injury, and/or epilepsy
- •Undergoing concurrent physical therapy
- •Cirrhosis Caffeine and/or NSAID allergies or intolerances
研究组 & 干预措施
Istradefylline+low oxygen training
Drug: Nourianz Other Names: KW6002, Istradefylline
Participants enrolled in this study arm will ingest a 20mg tablet/day containing istradefylline starting 14 days prior to the first low oxygen therapy and continuing for 14 additional days. Participants will consume a total of 28 istradefylline tablets.
Other: low oxygen training Other Names: therapeutic intermittent hypoxia, acute intermittent hypoxia
Participants will breathe 15 episodes/session of acute low oxygen via an automated air generator system (4 sessions/week x 2 weeks). During the 90-second episodes of low oxygen, air concentrations will be continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia) with 60-second room-air intervals (FIO2 0.21±0.02).
Throughout experimentation, blood pressure, respiratory rate, and heart rate will be monitored. We also will assess for changes in sleep quality and pain level.
干预措施: Istradefylline (Drug)
Istradefylline+low oxygen training
Drug: Nourianz Other Names: KW6002, Istradefylline
Participants enrolled in this study arm will ingest a 20mg tablet/day containing istradefylline starting 14 days prior to the first low oxygen therapy and continuing for 14 additional days. Participants will consume a total of 28 istradefylline tablets.
Other: low oxygen training Other Names: therapeutic intermittent hypoxia, acute intermittent hypoxia
Participants will breathe 15 episodes/session of acute low oxygen via an automated air generator system (4 sessions/week x 2 weeks). During the 90-second episodes of low oxygen, air concentrations will be continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia) with 60-second room-air intervals (FIO2 0.21±0.02).
Throughout experimentation, blood pressure, respiratory rate, and heart rate will be monitored. We also will assess for changes in sleep quality and pain level.
干预措施: low oxygen therapy (Device)
Placebo+low oxygen training
This is a placebo counterpart to the istradefylline drug.
Participants enrolled in this study arm will ingest a 20mg placebo tablet/day containing dextrose starting 14 days prior to the first low oxygen therapy (LOT) and continuing for 14 additional days. Participants will consume a total of 28 placebo tablets.
Other: low oxygen training Other Names: therapeutic intermittent hypoxia, acute intermittent hypoxia
Participants will breathe 15 episodes/session of acute low oxygen via an automated air generator system (4 sessions/week x 2 weeks). During the 90-second episodes of low oxygen, air concentrations will be continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia) with 60-second room-air intervals (FIO2 0.21±0.02).
Throughout experimentation, blood pressure, respiratory rate, and heart rate will be monitored. We also will assess for changes in sleep quality and pain level.
干预措施: low oxygen therapy (Device)
Istradefylline+SHAM
Drug: Nourianz Other Names: KW6002, Istradefylline
This is a SHAM counterpart to low oxygen therapy.
Participants enrolled in this study arm will ingest a 20mg tablet/day containing istradefylline starting 14 days prior to the first SHAM therapy and continuing for 14 additional days. Participants will consume a total of 28 istradefylline tablets.
Participants will breathe 15 episodes/session of SHAM via an automated air generator system (4 sessions/week x 2 weeks). The system will fill reservoir bags attached to a non-rebreathing face mask. During the 90-second episodes of SHAM, air concentrations will be continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.21±0.02 (normoxia) with 60-second room-air intervals (FIO2 0.21±0.02).
Throughout experimentation, blood pressure, respiratory rate, and heart rate will be monitored. We also will assess for changes in sleep quality and pain level.
干预措施: Istradefylline (Drug)
结局指标
主要结局
Walking Speed Post-Treatment 3
时间窗: between 17-20 days after Post-Treatment 1
Post-Treatment 10MWT (time, seconds)
Pre-Treatment Walking Speed
时间窗: within 5 days of first treatment
Pre-Treatment Walking Speed; 10MWT (time, seconds)
Walking Speed Post-Treatment 1
时间窗: within 1 day after last treatment
Post-Treatment Walking Speed; 10MWT (time, seconds)
Walking Speed Post-Treatment 2
时间窗: between 7-10 days after Post-Treatment 1
Post-Treatment Walking Speed; 10MWT (time, seconds)
次要结局
- Pre-treatment Ankle Strength(within 5 days of first treatment)
- Ankle Strength Post-Treatment 2(between 7-10 days after Post-Treatment 1)
- Pre-Treatment Walking Distance(within 5 days of first treatment)
- Walking Distance Post-Treatment 1(within 1 day after last treatment)
- Walking Distance Post-Treatment 2(between 7-10 days after Post-Treatment 1)
- Walking Distance Post-Treatment 3(between 17-20 days after Post-Treatment 1)
- Timed Up-and-Go Test Post-Treatment 2(between 7-10 days after Post-Treatment 1)
- Timed Up-and-Go Test Post-Treatment 3(between 17-20 days after Post-Treatment 1)
- Pre-Treatment Timed Up-and-Go Test(within 5 days of first treatment)
- Timed Up-and-Go Test Post-Treatment 1(within 1 day after last treatment)
- Ankle Strength Post-Treatment 1(within 1 day after last treatment)
- Ankle Strength Post-Treatment 3(between 17-20 days after Post-Treatment 1)
研究者
Randy Trumbower, PT, PhD
Assistant Professor
Spaulding Rehabilitation Hospital