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

NCT05217498 | Not Yet Recruiting Phase 1 FDA Drug FDA Device

• 1 other identifier: 2018A004512
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Spinal Cord Injuries; Myelopathy

Keywords

spinal cord injury; walking; motor control; istradefylline; adenosine; strength

Outcome Measures

Primary Outcomes (4)

• Pre-Treatment Walking Speed

  Pre-Treatment Walking Speed; 10MWT (time, seconds)

  within 5 days of first treatment

• Walking Speed Post-Treatment 1

  Post-Treatment Walking Speed; 10MWT (time, seconds)

  within 1 day after last treatment

• Walking Speed Post-Treatment 2

  Post-Treatment Walking Speed; 10MWT (time, seconds)

  between 7-10 days after Post-Treatment 1

• Walking Speed Post-Treatment 3

  Post-Treatment 10MWT (time, seconds)

  between 17-20 days after Post-Treatment 1

Secondary Outcomes (12)

• 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

• Pre-Treatment Timed Up-and-Go Test

  within 5 days of first treatment

Study Arms (3)

Istradefylline+low oxygen training

EXPERIMENTAL

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.

Drug: Istradefylline; Device: low oxygen therapy

Placebo+low oxygen training

ACTIVE COMPARATOR

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.

Device: low oxygen therapy

Istradefylline+SHAM

ACTIVE COMPARATOR

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.

Drug: Istradefylline

Interventions

Istradefylline DRUG

Consume 20mg tablet of istradefylline for 28 consecutive days.

Also known as: KW6002, Nourianz

Istradefylline+SHAM; Istradefylline+low oxygen training

low oxygen therapy 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.

Also known as: acute intermittent hypoxia

Istradefylline+low oxygen training; Placebo+low oxygen training

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Randy Trumbower, PT, PhD: lead

Study Sites (1)

Spaulding Rehabilitation Hospital

Cambridge, Massachusetts, 02138, United States

Location

Related Publications (7)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

Related Links

• Research Lab Website

MeSH Terms

Conditions

Spinal Cord Injuries; Spinal Cord Diseases

Interventions

istradefylline

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Randy D Trumbower, PT, PhD

  Spaulding Rehabilitation Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Randy D. Trumbower, PT, PhD

CONTACT

6179526953; randy.trumbower@mgh.harvard.edu

William Muter

CONTACT

6179526953; wmuter@partners.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: February 1, 2022
• Study Start (Estimated): September 1, 2027
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)