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

NCT ID: NCT05217498

Last Updated: 2025-10-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2027-09-01

Study Completion Date

2028-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Spinal Cord Injuries Myelopathy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

Istradefylline

Intervention Type DRUG

Consume 20mg tablet of istradefylline for 28 consecutive days.

low oxygen therapy

Intervention Type DEVICE

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.

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.

Group Type ACTIVE_COMPARATOR

low oxygen therapy

Intervention Type DEVICE

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.

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.

Group Type ACTIVE_COMPARATOR

Istradefylline

Intervention Type DRUG

Consume 20mg tablet of istradefylline for 28 consecutive days.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Istradefylline

Consume 20mg tablet of istradefylline for 28 consecutive days.

Intervention Type DRUG

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.

Intervention Type DEVICE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

KW6002 Nourianz acute intermittent hypoxia

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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 because of the unknown effects of AIH on pregnant women and fetus
3. History of seizures, brain injury, and/or epilepsy
4. Undergoing concurrent physical therapy
5. Diabetes
6. Cirrhosis Caffeine and/or NSAID allergies or intolerances
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Randy Trumbower, PT, PhD

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Randy Trumbower, PT, PhD

Assistant Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Randy D Trumbower, PT, PhD

Role: PRINCIPAL_INVESTIGATOR

Spaulding Rehabilitation Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Spaulding Rehabilitation Hospital

Cambridge, Massachusetts, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Randy D. Trumbower, PT, PhD

Role: CONTACT

6179526953

William Muter

Role: CONTACT

6179526953

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 21821826 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32682613 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33738145 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24285617 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28972191 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32369393 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33647273 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

https://www.inspire-lab.org

Research Lab Website

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2018A004512

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Improving Walking After Spinal Cord Injury
NCT07223710 NOT_YET_RECRUITING PHASE1/PHASE2
Treadmill Training for Spinal Cord Injury
NCT00006429 COMPLETED PHASE2
FLO2 for Recovery After SCI
NCT03833674 COMPLETED NA