AIH-induced Walking Recovery After Subacute SCI

May 9, 2024 updated by: Randy Trumbower, PT, PhD, Spaulding Rehabilitation Hospital

Intermittent Hypoxia-Induced Recovery of Overground Walking in Persons With Subacute SCI

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

125

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30309
        • Shepherd Center
    • Massachusetts
      • Cambridge, Massachusetts, United States, 02138
        • Spaulding Rehabilitation Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Specific inclusion/exclusion criteria for recruiting non-ambulatory subjects:

Participation in this group requires all of the above inclusion/exclusion criteria, as well as being unable to complete any of the below measures:

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

Specific inclusion/exclusion criteria for recruiting ambulatory subjects:

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Other: 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).
Sham Comparator: 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.
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).
Experimental: 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.
Other: 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).
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
Sham Comparator: 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.
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).
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
Other: Ambulatory-Walk
Ambulatory subjects will be randomly assigned to 10 sessions of walking practice only for 5 consecutive sessions/week x 2 weeks.
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in walking recovery, assessed by timed up-and-go (TUG) test
Time Frame: Baseline, Post-session 10 (up to two weeks)
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)
Time Frame: Baseline, Post-session 10 (up to two weeks)
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)
Time Frame: Baseline, Post-session 10 (up to two weeks)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in pain severity
Time Frame: Baseline, Post-session 10 (up to two weeks)
Participants will report their pain level using the Wong-Baker FACES scale. The scale is from 0 to 5; 0 being no pain and 5 being extreme pain. Change is the difference between the end of session 10 and baseline.
Baseline, Post-session 10 (up to two weeks)
Change in spasticity
Time Frame: Baseline, Post-session 10 (up to two weeks)
Spasticity will be assessed using the Spinal Cord Assessment Tool for Spastic Reflexes (SCATS). The study team will quantify the total lower extremity spasticity score using the cumulative sum of 3 SCATS subscales: clonus (0=no spasticity; 3=severe), flexor (0=no spasticity; 3=severe), and extensor (0=no spasticity; 3=severe). Change is the difference between the end of session 10 and baseline.
Baseline, Post-session 10 (up to two weeks)
Systemic hypertension incidence rate
Time Frame: Post-session 10 (up to two weeks)
Participants will have their systolic and diastolic blood pressure measured. A systemic hypertensive event is quantified as a systolic pressure exceeding 140mmHg and/or diastolic pressure exceeding 90mmHg. A hypertension incident rate is the number of hypertensive events divided by the total person-time. Person-time is in units of person-measures (the sum of the total number of BP measurements) taken for each person. Person-measures accounts for the total number of chances for detecting a hypertensive event and accounts for measurements not made due to drop-out or a disqualifying adverse event
Post-session 10 (up to two weeks)
Autonomic dysreflexia incidence rate
Time Frame: Post-session 10 (up to two weeks)
The occurrence of autonomic dysreflexia will be assessed. An autonomic dysreflexia event will constitute a participant having a systolic blood pressure (SBP) increase from baseline of 20mmHg or SBP greater than 150mmHg with complaints of headache, diaphoresis, and/or blurred vision and will be diagnosed by the study team clinicians.
Post-session 10 (up to two weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Spaulding Rehabilitation Hospital

Collaborators

United States Department of Defense

Investigators

  • Principal Investigator: Randy Trumbower, PT, PhD, Harvard Medical School (HMS and HSDM)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2015

Primary Completion (Actual)

July 7, 2023

Study Completion (Estimated)

December 30, 2024

Study Registration Dates

First Submitted

December 14, 2015

First Submitted That Met QC Criteria

December 15, 2015

First Posted (Estimated)

December 16, 2015

Study Record Updates

Last Update Posted (Actual)

May 10, 2024

Last Update Submitted That Met QC Criteria

May 9, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017P001941

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Study Data/Documents

  1. Informed Consent Form
    Information comments: Requests for study informed consent may be made using the lab's contact form.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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