Spinal Cord InjuriesNCT02274116
Acute Intermittent Hypoxia on Leg Function Following Spinal Cord Injury
A study testing AIH - Intermittent Hypoxia - hypoxia air mixture in people with Spinal Cord Injuries, run by Spaulding Rehabilitation Hospital at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Spinal Cord Injuries
- What is being tested?
- AIH - Intermittent Hypoxia - hypoxia air mixture
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Spaulding Rehabilitation Hospital
Cambridge, Massachusetts, 02138
About this study
Official title: 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
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 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.
- Conditions
- Spinal Cord Injuries
- Being tested
- SHAM - Intermittent Room Air - room air mixture, AIH - Intermittent Hypoxia - hypoxia air mixture
- Keywords
- acute intermittent hypoxia, walking, spasticity, incomplete spinal cord injury, breathing, strength
- Medical subject headings
- Spinal Cord Injuries, Muscle Spasticity, Respiratory Aspiration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SHAM - Intermittent Room Air - room air mixtureOther
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.
AIH - Intermittent Hypoxia - hypoxia air mixtureOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Intermittent Hypoxia (AIH) | Active comparator | 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 Receives: Other: AIH - Intermittent Hypoxia - hypoxia air mixture |
| Intermittent Room Air (SHAM) | Sham comparator | 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 Receives: Other: SHAM - Intermittent Room Air - room air mixture |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in overground walking endurance
walking endurance (6 minute walk test - how far one can walk in 6 minutes)
Measured: Baseline, immediately following intervention (day 5), and at 1, 2, and 4 weeks
Secondary outcomes (1)
Change in overground walking speed
walking speed (10 meter walk test - how fast one can walk in 10 meters)
Measured: Baseline, immediately following intervention (day 5), and at 1, 2, and 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 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 (4)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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Spaulding Rehabilitation Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation Wings For Life
- Responsible party
- Principal investigator, Randy Trumbower, PT, PhD, Spaulding Rehabilitation Hospital
- Investigators
- Randy D Trumbower, PT, PhD, Principal investigator, Spaulding Rehabilitation Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02274116
- Sponsor's protocol ID
- 2017P001940c
- Status last verified
- Mar 2026
- First submitted
- 6 Oct 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 21821826Lovett-Barr MR, Satriotomo I, Muir GD, Wilkerson JE, Hoffman MS, Vinit S, Mitchell GS. Repetitive intermittent hypoxia induces respiratory and somatic motor recovery after chronic cervical spinal injury. J Neurosci. 2012 Mar 14;32(11):3591-600. doi: 10.1523/JNEUROSCI.2908-11.2012.
PubMed 22423083Dale-Nagle EA, Hoffman MS, MacFarlane PM, Satriotomo I, Lovett-Barr MR, Vinit S, Mitchell GS. Spinal plasticity following intermittent hypoxia: implications for spinal injury. Ann N Y Acad Sci. 2010 Jun;1198:252-9. doi: 10.1111/j.1749-6632.2010.05499.x.
PubMed 20536940
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
- Repetitive Exposure of Intermittent Hypoxia to Enhance Walking Recovery in Persons With Chronic Spinal Cord Injury
- ClinicalTrials.gov ID
- NCT02274116
- Acronym / sponsor ID
- 2017P001940c
- Conditions
- Spinal Cord Injuries
- Keywords
- acute intermittent hypoxia, walking, spasticity, incomplete spinal cord injury, breathing, strength
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Spaulding Rehabilitation HospitalUniversity, hospital or other
- Collaborators
- Foundation Wings For Life
- Study start
- Oct 2014
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Nov 2027 (estimated)
- First posted
- 24 Oct 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.
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
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 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 |
|---|---|---|
| Intermittent Hypoxia (AIH) | Active comparator | Other: AIH - Intermittent Hypoxia - hypoxia air mixtureSubjects 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 |
| Intermittent Room Air (SHAM) | Sham comparator | Other: SHAM - Intermittent Room Air - room air mixtureSubjects 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
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 |
|---|---|---|
| SHAM - Intermittent Room Air - room air mixtureParticipants 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. | Other | Intermittent Room Air (SHAM) |
| AIH - Intermittent Hypoxia - hypoxia air mixtureParticipants 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. | Other | Intermittent Hypoxia (AIH) |
Primary outcome
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)
1 secondary outcome
Change in overground walking speed
Time frame: Baseline, immediately following intervention (day 5), and at 1, 2, and 4 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 22423083Lovett-Barr MR, Satriotomo I, Muir GD, Wilkerson JE, Hoffman MS, Vinit S, Mitchell GS. Repetitive intermittent hypoxia induces respiratory and somatic motor recovery after chronic cervical spinal injury. J Neurosci. 2012 Mar 14;32(11):3591-600. doi: 10.1523/JNEUROSCI.2908-11.2012.
- Background: PubMed 20536940Dale-Nagle EA, Hoffman MS, MacFarlane PM, Satriotomo I, Lovett-Barr MR, Vinit S, Mitchell GS. Spinal plasticity following intermittent hypoxia: implications for spinal injury. Ann N Y Acad Sci. 2010 Jun;1198:252-9. doi: 10.1111/j.1749-6632.2010.05499.x.
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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. This study is not recruiting at the moment.
Randy D Trumbower, PT, PhD principal investigator
Spaulding Rehabilitation Hospital
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 - Intermittent Hypoxia - hypoxia air mixture 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 6 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: under way, not looking for participants, 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. Some participants in this study may receive a placebo. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in overground walking endurance (time frame: Baseline, immediately following intervention (day 5), and at 1, 2, and 4 weeks). 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 NCT02274116, which also lists 4 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.