Effects of Breathing Mild Bouts of Low Oxygen on Limb Mobility After Spinal Injury

NCT ID: NCT02323945

Last Updated: 2025-10-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-10-31

Study Completion Date

2027-11-30

Brief Summary

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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 (SCI). The goal of the study is to understand the mechanisms by which intermittent hypoxia enhances motor function and spinal plasticity (ability of the nervous system to strengthen neural pathways based on new experiences) following SCI.

Detailed Description

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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 questions remain. First, does intermittent hypoxia improve walking recovery by increasing strength or muscle coordination or both? Understanding its mechanisms will allow us to best apply intermittent hypoxia in the clinic. Second, initial studies indicate that the beneficial effects of intermittent hypoxia are greatest when intermittent hypoxia is used just prior to task training and that the benefits are greatest for the practiced task. The investigators will explore this possibility by examining the effects of intermittent hypoxia on walking ability and force production when applied alone and when applied in combination with walking training or strength training. The investigators expect to observe the greatest improvements in walking ability in those individuals receiving intermittent hypoxia with walking training and the greatest improvements in strength in response to intermittent hypoxia with strength training. Third, studies suggest that intermittent hypoxia induces spinal plasticity by increasing the expression of a key plasticity-promoting protein, brain-derived neurotrophic factor (BDNF). Mutations in the BDNF gene have been shown to impair BDNF functionality. Thus, the investigators will also explore the impact of BDNF polymorphisms on responsiveness to intermittent hypoxia therapy.

Conditions

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Spinal Cord Injuries

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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AIH/Walk

Subjects with chronic, motor-incomplete SCI receive acute intermittent hypoxia (AIH) with walking practice, then AIH with strength practice and compare their efficacy on enhancing strength and/or walking performance.

Group Type ACTIVE_COMPARATOR

AIH

Intervention Type OTHER

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 on 5 consecutive days.

Walk

Intervention Type OTHER

30 minutes of walking practice consisting of 5 repetitions of 6-minute walks

AIH/Strength

Subjects with chronic, motor-incomplete SCI receive AIH with strength practice, then AIH with walking practice and compare their efficacy on enhancing strength and/or walking performance.

Group Type ACTIVE_COMPARATOR

AIH

Intervention Type OTHER

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 on 5 consecutive days.

Strength

Intervention Type OTHER

30 minutes of isometric ankle plantar flexion torque practice broken into 3 sets of 10 repetitions

Interventions

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AIH

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 on 5 consecutive days.

Intervention Type OTHER

Walk

30 minutes of walking practice consisting of 5 repetitions of 6-minute walks

Intervention Type OTHER

Strength

30 minutes of isometric ankle plantar flexion torque practice broken into 3 sets of 10 repetitions

Intervention Type OTHER

Other Intervention Names

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Acute Intermittent Hypoxia

Eligibility Criteria

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Inclusion Criteria

* Age 18 and 75 years (the latter to reduce 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 1 year

Exclusion Criteria

* 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 affects 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Foundation Wings For Life

OTHER

Sponsor Role collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

Spaulding Rehabilitation Hospital

OTHER

Sponsor Role lead

Responsible Party

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Randy Trumbower, PT, PhD

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Randy D Trumbower, PT, PhD

Role: PRINCIPAL_INVESTIGATOR

Harvard Medical School (HMS and HSDM)

Locations

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Spaulding Rehabilitation Hospital

Cambridge, Massachusetts, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Randy D Trumbower, PT, PhD

Role: CONTACT

617-952-6951

Stella Barth, BA

Role: CONTACT

617-952-6822

Facility Contacts

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Randy D Trumbower, PT, PhD

Role: primary

(617) 952-6951

Melissa DeChellis, BA

Role: backup

(617) 952-6953

References

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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)

Hoffman MS, Golder FJ, Mahamed S, Mitchell GS. Spinal adenosine A2(A) receptor inhibition enhances phrenic long term facilitation following acute intermittent hypoxia. J Physiol. 2010 Jan 1;588(Pt 1):255-66. doi: 10.1113/jphysiol.2009.180075. Epub 2009 Nov 9.

Reference Type BACKGROUND
PMID: 19900961 (View on PubMed)

Baker-Herman TL, Fuller DD, Bavis RW, Zabka AG, Golder FJ, Doperalski NJ, Johnson RA, Watters JJ, Mitchell GS. BDNF is necessary and sufficient for spinal respiratory plasticity following intermittent hypoxia. Nat Neurosci. 2004 Jan;7(1):48-55. doi: 10.1038/nn1166. Epub 2003 Dec 14.

Reference Type BACKGROUND
PMID: 14699417 (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)

Other Identifiers

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1R01HD081274-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2017P001940a

Identifier Type: -

Identifier Source: org_study_id

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