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Not yet recruiting NCT05217498

Combining Low Oxygen Therapy and an Adenosine A2a Receptor Antagonist to Improve Functional Mobility After Spinal Cord Injury

Phase I / Phase II Interventional Spinal Cord Injuries Myelopathy

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Istradefylline, low oxygen therapy.
Who it may be relevant to
Registry conditions: Spinal Cord Injuries, Myelopathy. Basic parameters: 18 years — 75 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

A Selective Adenosine 2a Antagonist to Enhance Training-related Gains in Walking Function for Persons With Chronic, Incomplete Spinal Cord Injury

Overview

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.

Detailed 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 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).

Blood samples will be collected at baseline, and at the end of week 2, week 4 to assess for potential confounding effects of systemic inflammation and caffeine on responsiveness to the combinatorial interventions.

The study will assess functional outcomes, vital signs, and symptoms before and after each intervention. For our primary outcome measure, the study will assess walking speed (10-meter walk test, 10MWT) relative to baseline at the end of day 5 (D5), and 8 (F1) and 14 days (F2) post-treatment. This study also will assess leg strength, walking distance, and coordination on D5, F1, and F2 as secondary outcome measures. A linear mixed model will be used to compare differences in 10MWT with treatment and time as main effects and participants as random effects. This study will follow the Consolidated Standards of Reporting Trials.

Interventions

  • Drug Istradefylline
    Consume 20mg tablet of istradefylline for 28 consecutive days.
  • Device low 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.

Primary outcome measures

  • Pre-Treatment Walking Speed [Time frame: within 5 days of first treatment]
  • Walking Speed Post-Treatment 1 [Time frame: within 1 day after last treatment]
  • Walking Speed Post-Treatment 2 [Time frame: between 7-10 days after Post-Treatment 1]
  • Walking Speed Post-Treatment 3 [Time frame: between 17-20 days after Post-Treatment 1]
Secondary outcome measures (12)
  • Pre-Treatment Walking Distance [Time frame: within 5 days of first treatment]
  • Walking Distance Post-Treatment 1 [Time frame: within 1 day after last treatment]
  • Walking Distance Post-Treatment 2 [Time frame: between 7-10 days after Post-Treatment 1]
  • Walking Distance Post-Treatment 3 [Time frame: between 17-20 days after Post-Treatment 1]
  • Pre-Treatment Timed Up-and-Go Test [Time frame: within 5 days of first treatment]
  • Timed Up-and-Go Test Post-Treatment 1 [Time frame: within 1 day after last treatment]
  • Timed Up-and-Go Test Post-Treatment 2 [Time frame: between 7-10 days after Post-Treatment 1]
  • Timed Up-and-Go Test Post-Treatment 3 [Time frame: between 17-20 days after Post-Treatment 1]
  • Pre-treatment Ankle Strength [Time frame: within 5 days of first treatment]
  • Ankle Strength Post-Treatment 1 [Time frame: within 1 day after last treatment]
  • Ankle Strength Post-Treatment 2 [Time frame: between 7-10 days after Post-Treatment 1]
  • Ankle Strength Post-Treatment 3 [Time frame: between 17-20 days after Post-Treatment 1]

Eligibility criteria

Inclusion criteria

  • 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

Exclusion criteria

  • 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
  • Diabetes
  • Cirrhosis Caffeine and/or NSAID allergies or intolerances

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Crossover
Masking
Triple blind
Primary purpose
Treatment

Study locations

United States · 1 center
  • Spaulding Rehabilitation Hospital — Cambridge

Publications

  • Trumbower RD, Jayaraman A, Mitchell GS, Rymer WZ. Exposure to acute intermittent hypoxia augments somatic motor function in humans with incomplete spinal cord injury. Neurorehabil Neural Repair. 2012 Feb;26(2):163-72. doi: 10.1177/1545968311412055. Epub 2011 Aug 5. PMID 21821826
  • Tan AQ, Papadopoulos JM, Corsten AN, Trumbower RD. An automated pressure-swing absorption system to administer low oxygen therapy for persons with spinal cord injury. Exp Neurol. 2020 Nov;333:113408. doi: 10.1016/j.expneurol.2020.113408. Epub 2020 Jul 17. PMID 32682613
  • Tan AQ, Barth S, Trumbower RD. Acute intermittent hypoxia as a potential adjuvant to improve walking following spinal cord injury: evidence, challenges, and future directions. Curr Phys Med Rehabil Rep. 2020 Sep;8(3):188-198. doi: 10.1007/s40141-020-00270-8. Epub 2020 Jun 24. PMID 33738145
  • Hayes HB, Jayaraman A, Herrmann M, Mitchell GS, Rymer WZ, Trumbower RD. Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. Neurology. 2014 Jan 14;82(2):104-13. doi: 10.1212/01.WNL.0000437416.34298.43. Epub 2013 Nov 27. PMID 24285617
  • Trumbower RD, Hayes HB, Mitchell GS, Wolf SL, Stahl VA. Effects of acute intermittent hypoxia on hand use after spinal cord trauma: A preliminary study. Neurology. 2017 Oct 31;89(18):1904-1907. doi: 10.1212/WNL.0000000000004596. Epub 2017 Sep 29. PMID 28972191
  • Vivodtzev I, Tan AQ, Hermann M, Jayaraman A, Stahl V, Rymer WZ, Mitchell GS, Hayes HB, Trumbower RD. Mild to Moderate Sleep Apnea Is Linked to Hypoxia-induced Motor Recovery after Spinal Cord Injury. Am J Respir Crit Care Med. 2020 Sep 15;202(6):887-890. doi: 10.1164/rccm.202002-0245LE. No abstract available. PMID 32369393
  • Tan AQ, Sohn WJ, Naidu A, Trumbower RD. Daily acute intermittent hypoxia combined with walking practice enhances walking performance but not intralimb motor coordination in persons with chronic incomplete spinal cord injury. Exp Neurol. 2021 Jun;340:113669. doi: 10.1016/j.expneurol.2021.113669. Epub 2021 Feb 27. PMID 33647273

Identifiers

NCT: NCT05217498 · 2018A004512

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗