NCT02632422

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
125

participants targeted

Target at P50-P75 for not_applicable

Timeline
20mo left

Started Oct 2015

Longer than P75 for not_applicable

Geographic Reach
1 country

2 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress87%
Oct 2015Dec 2027

Study Start

First participant enrolled

October 1, 2015

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

December 14, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 16, 2015

Completed
7.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 7, 2023

Completed
4.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2027

Expected
Last Updated

October 31, 2025

Status Verified

October 1, 2025

Enrollment Period

7.8 years

First QC Date

December 14, 2015

Last Update Submit

October 29, 2025

Conditions

Keywords

walkrehabilitationstrengthmovementspinal cord traumaspinal cord injury

Outcome Measures

Primary Outcomes (3)

  • Change in walking recovery, assessed by timed up-and-go (TUG) test

    The TUG test is used to assess the dynamic balance of an individual. It measures the amount of time (recorded in seconds) it takes for the individual to rise from a standard arm chair, walk a distance of 3 meters and return to the initial position resting against the back of the chair. Participants will perform up to three trials of the TUG test. Average speed across TUG trials will be used for analysis. Change is the difference between the end of session 10 and baseline.

    Baseline, Post-session 10 (up to two weeks)

  • Change in walking recovery, assessed by 6 minute walk test (6MWT)

    Participants perform the 6MWT at their fastest, most comfortable walking speed sustainable for 6 minutes. Distances will be recorded at 2 and 6 minutes. The test will be based upon the participant's ability to finish each assessment without human assistance. Change is the difference between the end of session 10 and baseline.

    Baseline, Post-session 10 (up to two weeks)

  • Change in walking recovery, assessed by 10 meter walk test (10MWT)

    Participants walk ten meters without assistance at their fastest, but safest speed with a minimum of 1-minute of rest between two trials. Average speed across the up to three 10MWT trials will be used for analysis. Change is the difference between the end of session 10 and baseline.

    Baseline, Post-session 10 (up to two weeks)

Secondary Outcomes (4)

  • Change in pain severity

    Baseline, Post-session 10 (up to two weeks)

  • Change in spasticity

    Baseline, Post-session 10 (up to two weeks)

  • Systemic hypertension incidence rate

    Post-session 10 (up to two weeks)

  • Autonomic dysreflexia incidence rate

    Post-session 10 (up to two weeks)

Study Arms (5)

Non-ambulatory - dAIH

EXPERIMENTAL

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.

Other: Daily acute intermittent hypoxia (dAIH)

Non-ambulatory - dSHAM

SHAM COMPARATOR

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.

Other: dSHAM

Ambulatory - dAIH+Walk

EXPERIMENTAL

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.

Other: Daily acute intermittent hypoxia (dAIH)Other: Walking

Ambulatory - dSHAM+Walk

SHAM COMPARATOR

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.

Other: dSHAMOther: Walking

Ambulatory-Walk

OTHER

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

Other: Walking

Interventions

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).

Ambulatory - dAIH+WalkNon-ambulatory - dAIH
dSHAMOTHER

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 - dSHAM+WalkNon-ambulatory - dSHAM
WalkingOTHER

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 - dAIH+WalkAmbulatory - dSHAM+WalkAmbulatory-Walk

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • months post-injury (subacute)

You may not qualify if:

  • 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
  • meter walk test (10MWT)
  • 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
  • meter walk test (10MWT)
  • minute walk test (6MWT)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Shepherd Center

Atlanta, Georgia, 30309, United States

Location

Spaulding Rehabilitation Hospital

Cambridge, Massachusetts, 02138, United States

Location

Related Publications (8)

  • 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: 28972191BACKGROUND
  • 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: 24285617BACKGROUND
  • 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: 21821826BACKGROUND
  • 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.

    PMID: 24618214BACKGROUND
  • 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.

    PMID: 28762876BACKGROUND
  • 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.

    PMID: 29648987BACKGROUND
  • 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.

    PMID: 32641012BACKGROUND
  • 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.

Related Links

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

Walking

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesTrauma, Nervous SystemWounds and Injuries

Intervention Hierarchy (Ancestors)

LocomotionMovementMusculoskeletal Physiological PhenomenaMusculoskeletal and Neural Physiological PhenomenaExerciseMotor Activity

Study Officials

  • Randy Trumbower, PT, PhD

    Harvard Medical School (HMS and HSDM)

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

December 14, 2015

First Posted

December 16, 2015

Study Start

October 1, 2015

Primary Completion

July 7, 2023

Study Completion (Estimated)

December 30, 2027

Last Updated

October 31, 2025

Record last verified: 2025-10

Locations