Spinal Cord InjuriesNCT02323945
Effects of Breathing Mild Bouts of Low Oxygen on Limb Mobility After Spinal Injury
A study testing AIH, Walk and Strength in people with Spinal Cord Injuries, run by Spaulding Rehabilitation Hospital at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Spinal Cord Injuries
- What is being tested?
- AIH, Walk and Strength
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2014to Nov 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Spaulding Rehabilitation Hospital
Cambridge, Massachusetts, 02138
Randy D Trumbower, PT, PhD, (617) 952-6951, randy.trumbower@mgh.harvard.edu
Melissa DeChellis, BA, (617) 952-6953, mpierre19@partners.org
About this study
Official title: Mechanisms of Intermittent Hypoxia-induced Motor Recovery in Persons With SCI
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.
Read the 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 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
- Spinal Cord Injuries
- Being tested
- AIH, Walk, Strength
- Keywords
- acute intermittent hypoxia, incomplete spinal cord injury, strength, walking, breathing
- Medical subject headings
- Spinal Cord Injuries, Respiratory Aspiration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AIHOther
Also called Acute Intermittent Hypoxia
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.
WalkOther
30 minutes of walking practice consisting of 5 repetitions of 6-minute walks
StrengthOther
30 minutes of isometric ankle plantar flexion torque practice broken into 3 sets of 10 repetitions
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: AIH; Other: 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. Receives: Other: AIH; Other: Strength |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in overground walking endurance
Endurance will be measured as the distance walked during 2 min and 6 min (6MWT).
Measured: 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.
Measured: 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
Speed will be assessed by the time required to walk 10 meters (10MWT).
Measured: Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2014 (estimated)
- Study startOct 2014
- Primary completionAug 2027 (estimated)
- Study completionNov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Spinal Cord InjuriesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Spaulding Rehabilitation Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation Wings For Life, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Randy Trumbower, PT, PhD, Spaulding Rehabilitation Hospital
- Investigators
- Randy D Trumbower, PT, PhD, Principal investigator, Harvard Medical School (HMS and HSDM)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02323945
- Sponsor's protocol ID
- 2017P001940a
- Other IDs
- 1R01HD081274-01
- Status last verified
- Mar 2026
- First submitted
- 20 Nov 2014
- Last updated
- 20 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 24285617Trumbower 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.
PubMed 21821826Hoffman 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.
PubMed 19900961Baker-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.
PubMed 14699417Hayes 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.
PubMed 24618214Tan AQ, Tuthill C, Corsten AN, Barth S, Trumbower RD. A single sequence of intermittent hypoxia does not alter stretch reflex excitability in able-bodied individuals. Exp Physiol. 2024 Apr;109(4):576-587. doi: 10.1113/EP091531. Epub 2024 Feb 14.
PubMed 38356241
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Intermittent Hypoxia-induced Motor Recovery in Persons With SCI
- ClinicalTrials.gov ID
- NCT02323945
- Acronym / sponsor ID
- 2017P001940a
- Conditions
- Spinal Cord Injuries
- Keywords
- acute intermittent hypoxia, incomplete spinal cord injury, strength, walking, breathing
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Spaulding Rehabilitation HospitalUniversity, hospital or other
- Collaborators
- Foundation Wings For Life, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Oct 2014
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Nov 2027 (estimated)
- First posted
- 24 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AIH/Walk | Active comparator | Other: AIH, Other: WalkSubjects 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. |
| AIH/Strength | Active comparator | Other: AIH, Other: StrengthSubjects 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AIHAlso: Acute Intermittent HypoxiaParticipants 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. | Other | AIH/Strength, AIH/Walk |
| Walk30 minutes of walking practice consisting of 5 repetitions of 6-minute walks | Other | AIH/Walk |
| Strength30 minutes of isometric ankle plantar flexion torque practice broken into 3 sets of 10 repetitions | Other | AIH/Strength |
Primary outcome
Change in overground walking endurance
Time frame: Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks)
Endurance will be measured as the distance walked during 2 min and 6 min (6MWT).
Change in muscle strength
Time frame: Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks)
Strength will be assessed as the maximum isometric torque produced by the ankle and measured by a 6 degrees-of-freedom (DOF) load cell.
1 secondary outcome
Change in overground walking speed
Time frame: Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2026.
- Background: PubMed 24285617Hayes 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.
- Background: PubMed 21821826Trumbower 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.
- Background: PubMed 19900961Hoffman 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.
- Background: PubMed 14699417Baker-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.
- Background: PubMed 24618214Hayes 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.
- Derived from this study: PubMed 38356241Tan AQ, Tuthill C, Corsten AN, Barth S, Trumbower RD. A single sequence of intermittent hypoxia does not alter stretch reflex excitability in able-bodied individuals. Exp Physiol. 2024 Apr;109(4):576-587. doi: 10.1113/EP091531. Epub 2024 Feb 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Randy D Trumbower, PT, PhD principal investigator
Harvard Medical School (HMS and HSDM)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing AIH, Walk and Strength in people with Spinal Cord Injuries, run by Spaulding Rehabilitation Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Randy D Trumbower, PT, PhD (617-952-6951, randy.trumbower@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in overground walking endurance (time frame: Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02323945, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2026.