SCIEarly Phase 1NCT03780829
AIH for Spinal Cord Repair
A Early Phase 1 study testing hypoxia, D-cycloserine and exercise training in people with SCI, run by VA Office of Research and Development at 1 site in United States.
Trial summary
Contusive cervical spinal cord injury (cSCI) impairs upper limb function (reach-and-grasp) which limits daily-life activities and thus decreases the quality of life. Promoting neuroplasticity may support upper limb recovery after SCI. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- SCI
- What is being tested?
- hypoxia, D-cycloserine and exercise training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Feb 2020to 5 Feb 2026
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male and females Veterans between 18-85 years
- Chronic cSCI (1 yr of injury)
- Cervical injury at C8 or above
- Sensory function: impaired (score of 1) but not absent (score of 0) or intact (score of 2) innervations in dermatomes C6, C7 and C8 during light touch and pin prick stimulus using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) sensory scores
- Motor function: Able to grasp small objects with one hand and able to perform a visible precision grasp between the index finger and thumb
- Motor scores ISNCSCI: 1 to 4 but not 5 on finger flexors and finger abductors on the hand tested.
Show all 10Show fewer
- These criteria were selected to ensure that hand impairment will not interfere with the ability to perform training and proposed tests
- Male and females (18-80 years)
- Right handed
- Able to complete precision and power grips
Who cannot join
- Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease
- Any debilitating disease prior to the SCI that caused exercise intolerance
- Premorbid, ongoing major depression or psychosis, altered cognitive status
- History of head injury or stroke
- Metal plate in skull
- History of seizures
Show all 20Show fewer
- Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold such as antipsychotic drugs
- chlorpromazine
- clozapine
- or tricyclic antidepressants
- Pregnant females
- Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal cord disease as spinal stenosis, spina bifida or herniated cervical disk
- AIH Exclusion Criteria (in addition to the above listed exclusion criteria):
- resting heart rate > 120 bpm
- resting systolic blood pressure >180 mmHg
- resting diastolic blood pressure >100 mmHg
- self-reported history of unstable angina or myocardial infarction within the previous month
- resting SpO2 > or equal to 95%
- cardiopulmonary complications such as COPD
- Same as for SCI individuals
Trial locations and contacts
1 site in 1 country.
United States1 site
Edward Hines Jr. VA Hospital, Hines, IL
Hines, Illinois, 60141-3030
About this study
Official title: Repetitive Acute Intermittent Hypoxia for Spinal Cord Repair
Contusive cervical spinal cord injury (cSCI) impairs upper limb function (reach-and-grasp) which limits daily-life activities and thus decreases the quality of life. Promoting neuroplasticity may support upper limb recovery after SCI. Repetitive exposure to acute intermittent hypoxia (rAIH) combined with motor training promotes recovery of motor function after SCI; however, the overall effects of rAIH/training are limited. The investigators will use an adult rat model of long-term contusive cSCI to study novel approaches to enhance the effect of rAIH/training on forelimb function and study the neuronal substrate underlying the effects. The findings will be used to direct the development of more effective rAIH/training approaches for people with contusive, functionally incomplete, cSCI. Because deficits in upper limb function are a major problem after stroke, amyotrophic lateral sclerosis, multiple sclerosis, and other motor disorders, this work may also be relevant for patients with other types of central nervous system (CNS) lesions.
Read the detailed description
The overall goal is to develop effective, clinically applicable, approaches to restore upper limb function (reach-and-grasp) after chronic contusive cervical spinal cord injury (cSCI). Impairments in upper limb function significantly reduce the quality of life for people with cSCI. Reach-and-grasp actions in animals and humans are largely controlled by the corticospinal tract (CST). The investigators argue that promoting plasticity within the CST may support the recovery of upper limb function after cSCI. Repetitive exposure to acute intermittent hypoxia (rAIH) combined with motor training is a safe, minimally invasive, treatment that elicits neuroplasticity resulting in improved recovery after cSCI, but its overall effects remain limited. The main goals are to: 1) enhance rAIH/training-induced aftereffects on forelimb function and increase the understanding of the neuronal substrates in an adult rat model of chronic contusive cSCI, and 2) use this knowledge to guide the development of more effective rAIH/training approaches to improve upper limb function in humans with chronic contusive cSCI.
In Specific Aim 1, using an adult rat model of chronic contusive cSCI, the investigators will investigate the effects of rAIH frequency and dose on rAIH/training-mediated functional recovery of the impaired forelimb. Also, the investigators will combine rAIH/training with N-methyl-D-aspartate receptor (NMDA)-mediated synaptic plasticity through D-cycloserine treatment and study the effects on recovery of forelimb function. Immunocytochemistry with imaging techniques will be used to assess structural neuronal plasticity in the CST after rAIH/training. In Specific Aim 2, in people with chronic incomplete cSCI, guided by the findings in Specific Aim 1, the investigators will study the effects of rAIH frequency and concurrent D-cycloserine treatment on rAIH/training-mediated upper limb function recovery. The investigators will comprehensively analyze the effects of rAIH on the strength of electrophysiological and functional aftereffects in the upper limb.
The proposed research will provide new knowledge on rAIH/training-mediated functional and anatomical aftereffects (Specific Aim 1), which will be used to develop effective rAIH/training protocols for people with contusive, functionally incomplete, cSCI (Specific Aim 2). The data from the investigators' experiments may lead to clinically applicable approaches that improve arm and hand function recovery after chronic contusive cSCI, which would positively impact the quality of life of Veterans with cSCI. The relevance of this proposal is emphasized by the limited efficacy of current strategies to improve upper limb function after cSCI.
- Conditions
- SCI
- Being tested
- hypoxia, sham hypoxia, D-cycloserine, sham-NMDA agonist, exercise training
- Keywords
- spinal cord injury, hypoxia, plasticity
- Medical subject headings
- Spinal Cord Injuries, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hypoxiaBehavioural
intermittent cycles of normoxia-hypoxia
sham hypoxiaBehavioural
intermittent cycles of sham hypoxia
D-cycloserineDrug
Also called NMDA agonist
NMDA agonist treatment
sham-NMDA agonistDrug
sham-NMDA agonist treatment
exercise trainingBehavioural
bimanual massed practice training
| Study group | Role | What they receive |
|---|---|---|
| hypoxia plus training | Experimental | combined hypoxia treatment with exercise training Receives: Behavioral: hypoxia; Behavioral: exercise training |
| sham hypoxia plus training | Sham comparator | combined sham hypoxia treatment with exercise training Receives: Behavioral: sham hypoxia; Behavioral: exercise training |
| hypoxia plus training plus NMDA agonist | Experimental | combined hypoxia treatment with exercise training and with NMDA agonist treatment Receives: Behavioral: hypoxia; Drug: D-cycloserine; Behavioral: exercise training |
| hypoxia plus training plus sham NMDA agonist | Placebo comparator | combined hypoxia treatment with exercise training and with sham NMDA agonist treatment Receives: Behavioral: hypoxia; Drug: sham-NMDA agonist; Behavioral: exercise training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in grip strength
Grip strength will be measured using a hand-held dynamometer, with an average force (measured in dynes) taken over the course of three trials. A rest break is provided between trials. Strength testing will be completed bilaterally.
Measured: baseline, 1st week, 2nd week, 4th week, 8th week, and 12th week
Change in pinch strength
Pinch strength will be assessed using a digital pinch gauge (unit of Force= Newton). The minimum value of zero will be assigned when a participant cannot actively squeeze the pinch meter between the thumb and index finger. The mean value of total of 3 trials will be assessed, with a rest break provided between trials.
Measured: baseline, 1st week, 2nd week, 4th week, 8th week, and 12th week
Change in motor evoked potential size
Resting and active motor thresholds (RMT and AMT) will be tested in each of the muscles using a stimulator.
Measured: 30 minutes before and 30 minutes after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2018
- Study start25 Feb 2020
- Primary completion5 Feb 2026
- Study completion5 Feb 2026
Why it stopped: the study no longer has funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SCIStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- repetitive intermittent hypoxia treatment combined with exercise and/or NMDA agonist
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Martin Oudega, PhD, Principal investigator, Edward Hines Jr. VA Hospital, Hines, IL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03780829
- Sponsor's protocol ID
- B2848-R
- Status last verified
- Feb 2026
- First submitted
- 12 Dec 2018
- Last updated
- 27 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repetitive Acute Intermittent Hypoxia for Spinal Cord Repair
- ClinicalTrials.gov ID
- NCT03780829
- Acronym / sponsor ID
- B2848-R
- Conditions
- SCI
- Keywords
- spinal cord injury, hypoxia, plasticity
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: the study no longer has funding
- Enrolment
- 50 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 25 Feb 2020 (actual)
- Primary completion
- 5 Feb 2026 (actual)
- Study completion
- 5 Feb 2026 (actual)
- First posted
- 19 Dec 2018 (actual)
- 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.
Contusive cervical spinal cord injury (cSCI) impairs upper limb function (reach-and-grasp) which limits daily-life activities and thus decreases the quality of life. Promoting neuroplasticity may support upper limb recovery after SCI. Repetitive exposure to acute intermittent hypoxia (rAIH) combined with motor training promotes recovery of motor function after SCI; however, the overall effects of rAIH/training are limited. The investigators will use an adult rat model of long-term contusive cSCI to study novel approaches to enhance the effect of rAIH/training on forelimb function and study the neuronal substrate underlying the effects. The findings will be used to direct the development of more effective rAIH/training approaches for people with contusive, functionally incomplete, cSCI. Because deficits in upper limb function are a major problem after stroke, amyotrophic lateral sclerosis, multiple sclerosis, and other motor disorders, this work may also be relevant for patients with other types of central nervous system (CNS) lesions.
Detailed description
The overall goal is to develop effective, clinically applicable, approaches to restore upper limb function (reach-and-grasp) after chronic contusive cervical spinal cord injury (cSCI). Impairments in upper limb function significantly reduce the quality of life for people with cSCI. Reach-and-grasp actions in animals and humans are largely controlled by the corticospinal tract (CST). The investigators argue that promoting plasticity within the CST may support the recovery of upper limb function after cSCI. Repetitive exposure to acute intermittent hypoxia (rAIH) combined with motor training is a safe, minimally invasive, treatment that elicits neuroplasticity resulting in improved recovery after cSCI, but its overall effects remain limited. The main goals are to: 1) enhance rAIH/training-induced aftereffects on forelimb function and increase the understanding of the neuronal substrates in an adult rat model of chronic contusive cSCI, and 2) use this knowledge to guide the development of more effective rAIH/training approaches to improve upper limb function in humans with chronic contusive cSCI.
In Specific Aim 1, using an adult rat model of chronic contusive cSCI, the investigators will investigate the effects of rAIH frequency and dose on rAIH/training-mediated functional recovery of the impaired forelimb. Also, the investigators will combine rAIH/training with N-methyl-D-aspartate receptor (NMDA)-mediated synaptic plasticity through D-cycloserine treatment and study the effects on recovery of forelimb function. Immunocytochemistry with imaging techniques will be used to assess structural neuronal plasticity in the CST after rAIH/training. In Specific Aim 2, in people with chronic incomplete cSCI, guided by the findings in Specific Aim 1, the investigators will study the effects of rAIH frequency and concurrent D-cycloserine treatment on rAIH/training-mediated upper limb function recovery. The investigators will comprehensively analyze the effects of rAIH on the strength of electrophysiological and functional aftereffects in the upper limb.
The proposed research will provide new knowledge on rAIH/training-mediated functional and anatomical aftereffects (Specific Aim 1), which will be used to develop effective rAIH/training protocols for people with contusive, functionally incomplete, cSCI (Specific Aim 2). The data from the investigators' experiments may lead to clinically applicable approaches that improve arm and hand function recovery after chronic contusive cSCI, which would positively impact the quality of life of Veterans with cSCI. The relevance of this proposal is emphasized by the limited efficacy of current strategies to improve upper limb function after cSCI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- Model description
- repetitive intermittent hypoxia treatment combined with exercise and/or NMDA agonist
| Arm | Type | Receives |
|---|---|---|
| hypoxia plus training | Experimental | Behavioral: hypoxia, Behavioral: exercise trainingcombined hypoxia treatment with exercise training |
| sham hypoxia plus training | Sham comparator | Behavioral: sham hypoxia, Behavioral: exercise trainingcombined sham hypoxia treatment with exercise training |
| hypoxia plus training plus NMDA agonist | Experimental | Behavioral: hypoxia, Drug: D-cycloserine, Behavioral: exercise trainingcombined hypoxia treatment with exercise training and with NMDA agonist treatment |
| hypoxia plus training plus sham NMDA agonist | Placebo comparator | Behavioral: hypoxia, Drug: sham-NMDA agonist, Behavioral: exercise trainingcombined hypoxia treatment with exercise training and with sham NMDA agonist treatment |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male and females Veterans between 18-85 years
- Chronic cSCI (1 yr of injury)
- Cervical injury at C8 or above
- Sensory function: impaired (score of 1) but not absent (score of 0) or intact (score of 2) innervations in dermatomes C6, C7 and C8 during light touch and pin prick stimulus using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) sensory scores
- Motor function: Able to grasp small objects with one hand and able to perform a visible precision grasp between the index finger and thumb
Key exclusion criteria (20 listed)
- Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease
- Any debilitating disease prior to the SCI that caused exercise intolerance
- Premorbid, ongoing major depression or psychosis, altered cognitive status
- History of head injury or stroke
- Metal plate in skull
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 |
|---|---|---|
| hypoxiaintermittent cycles of normoxia-hypoxia | Behavioural | hypoxia plus training, hypoxia plus training plus NMDA agonist, hypoxia plus training plus sham NMDA agonist |
| sham hypoxiaintermittent cycles of sham hypoxia | Behavioural | sham hypoxia plus training |
| D-cycloserineAlso: NMDA agonistNMDA agonist treatment | Drug | hypoxia plus training plus NMDA agonist |
| sham-NMDA agonistsham-NMDA agonist treatment | Drug | hypoxia plus training plus sham NMDA agonist |
| exercise trainingbimanual massed practice training | Behavioural | hypoxia plus training, hypoxia plus training plus NMDA agonist, hypoxia plus training plus sham NMDA agonist, sham hypoxia plus training |
Primary outcome
Change in grip strength
Time frame: baseline, 1st week, 2nd week, 4th week, 8th week, and 12th week
Grip strength will be measured using a hand-held dynamometer, with an average force (measured in dynes) taken over the course of three trials. A rest break is provided between trials. Strength testing will be completed bilaterally.
Change in pinch strength
Time frame: baseline, 1st week, 2nd week, 4th week, 8th week, and 12th week
Pinch strength will be assessed using a digital pinch gauge (unit of Force= Newton). The minimum value of zero will be assigned when a participant cannot actively squeeze the pinch meter between the thumb and index finger. The mean value of total of 3 trials will be assessed, with a rest break provided between trials.
Change in motor evoked potential size
Time frame: 30 minutes before and 30 minutes after intervention
Resting and active motor thresholds (RMT and AMT) will be tested in each of the muscles using a stimulator.
Results and safety
The study was stopped early (reason given: the study no longer has funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2026.
- Individual participant dataSharing planned: No
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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.
Martin Oudega, PhD principal investigator
Edward Hines Jr. VA Hospital, Hines, IL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing hypoxia, D-cycloserine and exercise training in people with SCI, run by VA Office of Research and Development 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 10 inclusion and 20 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: stopped early, as of the sponsor's last update on 27 Feb 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: the study no longer has funding). Results are not available in the source record.
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 grip strength (time frame: baseline, 1st week, 2nd week, 4th week, 8th week, and 12th week). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Feb 2026.