NCT02323945

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

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

Enrollment
44

participants targeted

Target at P25-P50 for not_applicable

Timeline
18mo left

Started Oct 2014

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
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 Progress89%
Oct 2014Nov 2027

Study Start

First participant enrolled

October 1, 2014

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

November 20, 2014

Completed
1 month until next milestone

First Posted

Study publicly available on registry

December 24, 2014

Completed
12.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2027

Expected
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2027

Last Updated

March 20, 2026

Status Verified

March 1, 2026

Enrollment Period

12.8 years

First QC Date

November 20, 2014

Last Update Submit

March 18, 2026

Conditions

Spinal Cord Injuries

Keywords

acute intermittent hypoxiaincomplete spinal cord injurystrengthwalkingbreathing

Outcome Measures

Primary Outcomes (2)

  • Change in overground walking endurance

    Endurance will be measured as the distance walked during 2 min and 6 min (6MWT).

    Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks)

  • Change in muscle strength

    Strength will be assessed as the maximum isometric torque produced by the ankle and measured by a 6 degrees-of-freedom (DOF) load cell.

    Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks)

Secondary Outcomes (1)

  • Change in overground walking speed

    Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks)

Study Arms (2)

AIH/Walk

ACTIVE COMPARATOR

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.

Other: AIHOther: Walk

AIH/Strength

ACTIVE COMPARATOR

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.

Other: AIHOther: Strength

Interventions

AIHOTHER

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.

Also known as: Acute Intermittent Hypoxia
AIH/StrengthAIH/Walk
WalkOTHER

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

AIH/Walk
StrengthOTHER

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

AIH/Strength

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Spaulding Rehabilitation Hospital

Cambridge, Massachusetts, 02138, United States

RECRUITING

Related Publications (5)

  • 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

  • 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.

    PMID: 19900961BACKGROUND

  • 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.

    PMID: 14699417BACKGROUND

  • 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

MeSH Terms

Conditions

Spinal Cord InjuriesRespiratory Aspiration

Interventions

Insemination, Artificial, HomologousWalking

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesTrauma, Nervous SystemWounds and InjuriesRespiration DisordersRespiratory Tract DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Insemination, ArtificialReproductive Techniques, AssistedReproductive TechniquesTherapeuticsInvestigative TechniquesInseminationReproductionReproductive Physiological PhenomenaReproductive and Urinary Physiological PhenomenaLocomotionMovementMusculoskeletal Physiological PhenomenaMusculoskeletal and Neural Physiological PhenomenaExerciseMotor Activity

Study Officials

  • Randy D Trumbower, PT, PhD

    Harvard Medical School (HMS and HSDM)

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Randy D Trumbower, PT, PhD

CONTACT

617-952-6951randy.trumbower@mgh.harvard.edu

Stella Barth, BA

CONTACT

617-952-6822sbarth@partners.org

Study Design

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

Study Record Dates

First Submitted

November 20, 2014

First Posted

December 24, 2014

Study Start

October 1, 2014

Primary Completion (Estimated)

August 1, 2027

Study Completion (Estimated)

November 1, 2027

Last Updated

March 20, 2026

Record last verified: 2026-03

Locations

US(1)