Acute Intermittent Hypoxia on Leg Function Following Spinal Cord Injury

November 27, 2023 updated by: Randy Trumbower, PT, PhD, Spaulding Rehabilitation Hospital

Repetitive Exposure of Intermittent Hypoxia to Enhance Walking Recovery in Persons With Chronic Spinal Cord Injury

The purpose of this study is to determine how the nervous system controlling leg muscles is altered following spinal cord injury and how they may be affected by brief periods of low oxygen inhalation over time.

The investigators hypothesize:

  • Acute intermittent hypoxia (AIH) exposure will increase maximum voluntary leg strength in persons with incomplete cervical spinal cord injury (SCI)
  • AIH exposure will increase multijoint reflex excitability of leg muscles in persons with incomplete cervical SCI
  • AIH exposure will increase walking performance in persons with incomplete cervical SCI

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Accumulating evidence suggests that repeatedly breathing low oxygen levels for brief periods (termed intermittent hypoxia) is a safe and effective treatment strategy to promote meaningful functional recovery in persons with chronic spinal cord injury. Repetitive exposure to mild hypoxia triggers a cascade of events in the spinal cord, including new protein synthesis and increased sensitivity in the circuitry necessary for breathing and walking. Recently, the investigators demonstrated that daily (5 consecutive days) of intermittent hypoxia stimulated walking enhancement in persons with chronic spinal cord injury.

Despite these exciting findings, important clinical questions remain. For example, the investigators do not know if prolonged, but less intense intermittent hypoxia induces longer-lasting motor recovery as has been shown in rat models. The investigators hypothesize that repetitive exposures to modest bouts of low oxygen will enhance and prolong walking recovery in persons with chronic spinal cord injury. The investigators anticipate intermittent hypoxia-induced improvements in overground walking ability, likely due to greater balance in excitatory and inhibitory neural transmission. Whereas excitatory inputs drive walking, inhibitory inputs sculpt and coordinate muscle activity; yet so often remain compromised after chronic injury. Thus, the investigators also predict that repetitive exposures to intermittent hypoxia will result in improved inhibition and subsequently enhance muscle coordination during walking. The investigators will use multiple experimental approaches, including muscle electromyography, measurements of walking dynamics and stretch reflexes. Finally, it is critical to assure that repetitive exposures to intermittent hypoxia do not elicit pathologies characteristic of more severe, chronic hypoxia experienced by individuals with obstructive sleep apnea. The investigators will confirm that repetitive exposure to mild bouts of intermittent hypoxia is safe.

Study Type

Interventional

Enrollment (Estimated)

30

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 Contact

Study Contact Backup

Study Locations

  • United States
    • 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 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 18 to 75 years old (the latter to reduce likelihood of heart disease);
  • medically stable with clearance from physician to participate;
  • motor---incomplete SCI at C2---L5 with non---progressive etiology;
  • >6 months since SCI to ensure minimal confounds of spontaneous neurological recovery;
  • those classified as ambulatory must have the ability to advance one step overground without human assistance.

Exclusion Criteria:

  • concurrent illness, including unhealed decubiti, severe neuropathic or chronic pain syndrome, infection, cardiovascular disease, osteoporosis (history of fractures), active heterotopic ossification, or known history of peripheral nerve injury to legs;
  • less than 24 on the Mini-mental Exam;
  • recurrent autonomic dysreflexia
  • cardiopulmonary complications
  • concurrent physical therapy
  • pregnancy because of unknown effects of AIH on a fetus, although women will not otherwise be excluded

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: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Intermittent Hypoxia (AIH)

Subjects with chronic, motor-incomplete SCI will breath mild bouts of low oxygen.

Intervention: AIH - Intermittent Hypoxia - hypoxia air mixture Dosage: 10% oxygen Frequency: 1.5 minutes bouts of low oxygen with 1.0 minute intervals of room air Duration: 38 minutes
Other: AIH - Intermittent Hypoxia - hypoxia air mixture
Participants will breathe intermittent low oxygen via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of fraction of inspired oxygen (FIO2)=0.10±0.02 (hypoxia). Participants will receive treatment 5 times per week for 2 weeks.
Sham Comparator: Intermittent Room Air (SHAM)

Subjects with chronic, motor-incomplete SCI will breath mild bouts of room air.

Intervention: SHAM - Intermittent Room Air - room air mixture Dosage: 21% oxygen Frequency: 1.5 minutes bouts of room air with 1.0 minute intervals also of room air Duration: 38 minutes
Other: SHAM - Intermittent Room Air - room air mixture
Participants will breathe intermittent room air via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of fraction of inspired oxygen (FIO2)=0.21±0.02 (normoxia). Participants will receive treatment 5 times per week for 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in overground walking endurance
Time Frame: Baseline, immediately following intervention (day 5), and at 1, 2, and 4 weeks
walking endurance (6 minute walk test - how far one can walk in 6 minutes)
Baseline, immediately following intervention (day 5), and at 1, 2, and 4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in overground walking speed
Time Frame: Baseline, immediately following intervention (day 5), and at 1, 2, and 4 weeks
walking speed (10 meter walk test - how fast one can walk in 10 meters)
Baseline, immediately following intervention (day 5), and at 1, 2, and 4 weeks

Collaborators and Investigators

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

Sponsor

Spaulding Rehabilitation Hospital

Collaborators

Foundation Wings For Life

Investigators

  • Principal Investigator: Randy D Trumbower, PT, PhD, Spaulding Rehabilitation Hospital

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

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

October 1, 2014

Primary Completion (Estimated)

May 1, 2024

Study Completion (Estimated)

August 1, 2024

Study Registration Dates

First Submitted

October 6, 2014

First Submitted That Met QC Criteria

October 22, 2014

First Posted (Estimated)

October 24, 2014

Study Record Updates

Last Update Posted (Actual)

November 29, 2023

Last Update Submitted That Met QC Criteria

November 27, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017P001940c

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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