A Selective Adenosine 2a Antagonist to Enhance Training-related Gains in Walking Function for Persons With Chronic, Incomplete Spinal Cord Injury
Randy Trumbower, PT, PhD
Summary
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.
Description
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 i…
Eligibility
- Age range
- 18–75 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. age 18 and 75 years (the latter to reduce the likelihood of heart disease) medical clearance to participate 2. lesion at or below C2 and above T12 with non-progressive etiology 3. classified as motor-incomplete with visible volitional leg movement 4. injury greater than 12 months 5. ability to advance one step overground without human assistance Exclusion Criteria: 1. Concurrent severe medical illness (i.e., infection, cardiovascular disease, ossification, recurrent autonomic dysreflexia, unhealed decubiti, and history of pulmonary complications) 2. Pregnant women bec…
Interventions
- DrugIstradefylline
Consume 20mg tablet of istradefylline for 28 consecutive days.
- Devicelow oxygen therapy
Breath intermittent low oxygen 4 days/week over 2 consecutive weeks. Intermittent low oxygen consists of 15, 90-second episodes of breathing low oxygen at 10% oxygen with 60-second intervals at 21% oxygen.
Location
- Spaulding Rehabilitation HospitalCambridge, Massachusetts