AIH-induced Walking Recovery After Subacute SCI

NCT ID: NCT02632422

Last Updated: 2025-10-31

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 125 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2027-12-30

Brief Summary

The purpose of this study is to determine how mild breathing bouts of low oxygen may restore walking and leg strength in persons who have sustained a spinal cord injury.

Detailed Description

The goal of the study is to determine whether repeatedly breathing mild bouts of low oxygen for brief periods (termed acute intermittent hypoxia (AIH)) improves recovery of walking and strength after spinal cord injury. This idea stems from animal studies on respiration, in which investigators showed that mild AIH improves breathing in rats with spinal injuries. These studies showed that AIH induces plasticity, strengthening neural connections by increasing the production of key proteins and improving the sensitivity of spinal cord circuitry. The ultimate goal of this research is to assess the potential of mild AIH as a therapeutic approach not only in persons with chronic spinal cord injury but also in persons with subacute injury. By applying AIH during early stages of recovery, the investigators hope to expand the potential benefits of AIH to a broader range of persons with spinal injury, thereby improving functional independence and quality of life for servicemen and civilians.

Conditions

Spinal Cord Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Non-ambulatory - dAIH

Non-ambulatory subjects will be randomly assigned to receive 10 sessions of daily acute intermittent hypoxia (dAIH) 10 treatment visits at a frequency of 5 days each week for 2 weeks.

Group Type: EXPERIMENTAL

Daily acute intermittent hypoxia (dAIH)

Intervention Type: OTHER

Each participant will be exposed to 10 sessions of daily acute intermittent hypoxia (dAIH) via air generators. The generator will fill reservoir bags attached to a non-rebreathing facemask. Each session will consist of 15 episodes which include intervals of 1.5 minute hypoxia (FIO2=0.10±0.02, i.e. 10% O2) and 1 minute normoxia (FIO2=0.21±0.02). Participants will receive 5 consecutive days of daily acute intermittent hypoxia (dAIH).

Non-ambulatory - dSHAM

Non-ambulatory subjects will be randomly assigned to receive 10 sessions of daily room air (dSHAM) 10 treatment visits at a frequency of 5 days each week for 2 weeks.

Group Type: SHAM_COMPARATOR

dSHAM

Intervention Type: OTHER

Each participant will be exposed to 10 sessions of daily room air (dSHAM) via air generators. The generator will fill reservoir bags attached to a non-rebreathing facemask. Each session will consist of 15 episodes of 1.5 minute normoxia (FIO2=0.21±0.02). Participants will receive 5 consecutive days of daily room air (dSHAM).

Ambulatory - dAIH+Walk

Ambulatory subjects will be randomly assigned to receive 10 sessions of daily acute intermittent hypoxia (dAIH) coupled with 60 minutes of walking practice at a frequency of 5 days each week for 2 weeks.

Group Type: EXPERIMENTAL

Daily acute intermittent hypoxia (dAIH)

Intervention Type: OTHER

Each participant will be exposed to 10 sessions of daily acute intermittent hypoxia (dAIH) via air generators. The generator will fill reservoir bags attached to a non-rebreathing facemask. Each session will consist of 15 episodes which include intervals of 1.5 minute hypoxia (FIO2=0.10±0.02, i.e. 10% O2) and 1 minute normoxia (FIO2=0.21±0.02). Participants will receive 5 consecutive days of daily acute intermittent hypoxia (dAIH).

Walking

Intervention Type: OTHER

Participants will participate in 10 days of walking practice sessions. Walking practice sessions will immediately follow (within 60 minutes) the breathing intervention during training visits and will last for 60 minutes.

Walking practice will incorporate 5 walking-related tasks:

1. walking balance (e.g., walking with turns)

2. skilled walking tasks (e.g., negotiating obstacles)

3. walking with secondary task (e.g., walking and talking)

4. endurance

5. speed

Ambulatory - dSHAM+Walk

Ambulatory subjects will be randomly assigned to receive 10 sessions of daily room air (dSHAM) coupled with 60 minutes of walking practice at a frequency of 5 days each week for 2 weeks.

Group Type: SHAM_COMPARATOR

dSHAM

Intervention Type: OTHER

Each participant will be exposed to 10 sessions of daily room air (dSHAM) via air generators. The generator will fill reservoir bags attached to a non-rebreathing facemask. Each session will consist of 15 episodes of 1.5 minute normoxia (FIO2=0.21±0.02). Participants will receive 5 consecutive days of daily room air (dSHAM).

Walking

Intervention Type: OTHER

Participants will participate in 10 days of walking practice sessions. Walking practice sessions will immediately follow (within 60 minutes) the breathing intervention during training visits and will last for 60 minutes.

Walking practice will incorporate 5 walking-related tasks:

1. walking balance (e.g., walking with turns)

2. skilled walking tasks (e.g., negotiating obstacles)

3. walking with secondary task (e.g., walking and talking)

4. endurance

5. speed

Ambulatory-Walk

Ambulatory subjects will be randomly assigned to 10 sessions of walking practice only for 5 consecutive sessions/week x 2 weeks.

Group Type: OTHER

Walking

Intervention Type: OTHER

Participants will participate in 10 days of walking practice sessions. Walking practice sessions will immediately follow (within 60 minutes) the breathing intervention during training visits and will last for 60 minutes.

Walking practice will incorporate 5 walking-related tasks:

1. walking balance (e.g., walking with turns)

2. skilled walking tasks (e.g., negotiating obstacles)

3. walking with secondary task (e.g., walking and talking)

4. endurance

5. speed

Interventions

Daily acute intermittent hypoxia (dAIH)

Each participant will be exposed to 10 sessions of daily acute intermittent hypoxia (dAIH) via air generators. The generator will fill reservoir bags attached to a non-rebreathing facemask. Each session will consist of 15 episodes which include intervals of 1.5 minute hypoxia (FIO2=0.10±0.02, i.e. 10% O2) and 1 minute normoxia (FIO2=0.21±0.02). Participants will receive 5 consecutive days of daily acute intermittent hypoxia (dAIH).

Intervention Type: OTHER

dSHAM

Each participant will be exposed to 10 sessions of daily room air (dSHAM) via air generators. The generator will fill reservoir bags attached to a non-rebreathing facemask. Each session will consist of 15 episodes of 1.5 minute normoxia (FIO2=0.21±0.02). Participants will receive 5 consecutive days of daily room air (dSHAM).

Intervention Type: OTHER

Walking

Participants will participate in 10 days of walking practice sessions. Walking practice sessions will immediately follow (within 60 minutes) the breathing intervention during training visits and will last for 60 minutes.

Walking practice will incorporate 5 walking-related tasks:

1. walking balance (e.g., walking with turns)

2. skilled walking tasks (e.g., negotiating obstacles)

3. walking with secondary task (e.g., walking and talking)

4. endurance

5. speed

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 18 to 70 years old
• medically stable with medical clearance from physician to participate
• spinal cord injury (SCI) at or below C3 (phrenic sparing) and above L5 with at least motor function preserved below the neurologic level
• non-progressive etiology of spinal injury
• American Spinal Injury Association Impairment Scale (AIS) grade A-D
• 2-12 months post-injury (subacute)

Exclusion Criteria

• severe concurrent illness or pain, including unhealed decubiti, severe neuropathic or chronic pain syndrome, infection (e.g. bladder), hypertension, cardiovascular disease, pulmonary disease, severe osteoporosis (history of fractures), active heterotopic ossification in the lower extremities, or history of peripheral nerve injury in the legs
• score less than 24 on Mini-Mental Exam
• severe autonomic dysreflexia
• history of cardiovascular/pulmonary complications
• pregnancy
• severe obstructive sleep apnea (OSA), characterized by uncontrolled hypoxia and sleep fractionation

• timed up-and-go (TUG) test
• 10-meter walk test (10MWT)
• 6-minute walk test (6MWT)

Participation in this group requires all of the above criteria, as well as successful completion of at least one below measure:

• timed up-and-go (TUG) test
• 10-meter walk test (10MWT)
• 6-minute walk test (6MWT)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

Spaulding Rehabilitation Hospital

OTHER

Sponsor Role: lead

Responsible Party

Randy Trumbower, PT, PhD

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Randy Trumbower, PT, PhD

Role: PRINCIPAL_INVESTIGATOR

Harvard Medical School (HMS and HSDM)

Locations

Shepherd Center

Atlanta, Georgia, United States

Spaulding Rehabilitation Hospital

Cambridge, Massachusetts, United States

Countries

United States

References

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)

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, 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)

Hayes HB, Chvatal SA, French MA, Ting LH, Trumbower RD. Neuromuscular constraints on muscle coordination during overground walking in persons with chronic incomplete spinal cord injury. Clin Neurophysiol. 2014 Oct;125(10):2024-35. doi: 10.1016/j.clinph.2014.02.001. Epub 2014 Feb 14.

Reference Type: BACKGROUND

PMID: 24618214 (View on PubMed)

Peters DM, Thibaudier Y, Deffeyes JE, Baer GT, Hayes HB, Trumbower RD. Constraints on Stance-Phase Force Production during Overground Walking in Persons with Chronic Incomplete Spinal Cord Injury. J Neurotrauma. 2018 Feb 1;35(3):467-477. doi: 10.1089/neu.2017.5146. Epub 2017 Oct 27.

Reference Type: BACKGROUND

PMID: 28762876 (View on PubMed)

Sohn WJ, Tan AQ, Hayes HB, Pochiraju S, Deffeyes J, Trumbower RD. Variability of Leg Kinematics during Overground Walking in Persons with Chronic Incomplete Spinal Cord Injury. J Neurotrauma. 2018 Nov 1;35(21):2519-2529. doi: 10.1089/neu.2017.5538. Epub 2018 Jun 5.

Reference Type: BACKGROUND

PMID: 29648987 (View on PubMed)

Naidu A, Peters DM, Tan AQ, Barth S, Crane A, Link A, Balakrishnan S, Hayes HB, Slocum C, Zafonte RD, Trumbower RD. Daily acute intermittent hypoxia to improve walking function in persons with subacute spinal cord injury: a randomized clinical trial study protocol. BMC Neurol. 2020 Jul 8;20(1):273. doi: 10.1186/s12883-020-01851-9.

Reference Type: BACKGROUND

PMID: 32641012 (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: RESULT

PMID: 32682613 (View on PubMed)

Related Links

http://inspire-lab.org

INSPIRE Lab - mission is to inspire persons with paralysis to move again

Other Identifiers

2017P001941

Identifier Type: -

Identifier Source: org_study_id