Spinal Cord InjuriesMIH and ADNCT05351827
Mild Intermittent Hypoxia: A Prophylactic for Autonomic Dysfunction in Individuals With Spinal Cord Injuries
A study testing Mild Intermittent Hypoxia in people with Spinal Cord Injuries and Autonomic Dysreflexia, run by VA Office of Research and Development at 1 site in United States.
Trial summary
The prevalence of autonomic dysfunction and sleep disordered breathing (SDB) is increased in individuals with spinal cord injury (SCI). The loss of autonomic control results in autonomic dysreflexia (AD) and orthostatic hypotension (OH) which explains the increase in cardiovascular related mortality in these Veterans. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Spinal Cord Injuries, Autonomic Dysreflexia
- What is being tested?
- Mild Intermittent Hypoxia
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2022to 29 Oct 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Motor incomplete spinal cord injury at or above the 12th thoracic vertebrae
- Signs or symptoms of autonomic dysfunction (this will be determined by the Autonomic Dysfunction Following Spinal Cord Injury (ADFSCI) and ISAFSCI questions. The ADFSCI requires a score of 1 on questions 16 and 22, and the International Standards to document Autonomic Function following SCI (ISAFSCI) requires a score of 1 on any parameter)
- Chronic injuries (>1 year post injury)
Who cannot join
- Pregnant
- Smoker
- Drug addiction
- Complete spinal cord injury
- Spinal cord injury below the 6th thoracic vertebrae
- Insulin dependent diabetes
- Shift workers (i.e., disrupted circadian rhythm)
- Active skin breakdown or pressure sores
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
John D. Dingell VA Medical Center, Detroit, MI
Detroit, Michigan, 48201-1916
Gino Panza, PhD, (313) 576-1000 ext. 64414, Gino.Panza@va.gov
Erin Olgren, PhD MS, (313) 576-4448, erin.olgren@va.gov
About this study
The prevalence of autonomic dysfunction and sleep disordered breathing (SDB) is increased in individuals with spinal cord injury (SCI). The loss of autonomic control results in autonomic dysreflexia (AD) and orthostatic hypotension (OH) which explains the increase in cardiovascular related mortality in these Veterans. There is no effective prophylaxis for autonomic dysfunction. The lack of prophylactic treatment for autonomic dysfunction, and no best clinical practices for SDB in SCI, are significant health concerns for Veterans with SCI. Therefore, the investigators will investigate the effectiveness of mild intermittent hypoxia (MIH) as a prophylactic for autonomic dysfunction in patients with SCI. The investigators propose that MIH targets several mechanisms associated with autonomic control and the co-morbidities associated with SDB. Specifically, exposure to MIH will promote restoration of homeostatic BP control, which would be beneficial to participation in daily activities and independence in those with SCI.
Read the detailed description
Individuals with a spinal cord injury (SCI) above the 6th thoracic vertebrae experience severe autonomic dysfunction. These individuals lose the ability to control blood pressure (BP) during a noxious or non-noxious stimulus below the injury (Autonomic Dysreflexia [AD]) and during positional changes (Orthostatic Hypotension [OH]). The loss of descending autonomic control and subsequent loss of BP control are highly prevalent in individuals with SCI. More importantly, many individuals are unaware of the loss of BP control as most individuals remain asymptomatic. These potentially life-threatening oscillations in BP are known to induce further damage; creating a vicious cycle of continued autonomic and cardiovascular dysfunction which explains the increased cardiovascular related mortality. Unfortunately, there is no effect prophylaxis for autonomic dysfunction in these individuals. Furthermore, the prevalence of sleep disordered breathing (SDB) is high in individuals with SCI (tetraplegia can exceed 90%), and there is no current best clinical practice guidelines for treating SDB in individuals with SCI. The primary treatment is with continuous positive airway pressure (CPAP). Unfortunately, treatment adherence remains poor. Moreover, SDB is known to negatively impact autonomic, cardiovascular, and microvascular function in individuals without SCI. In individuals without an SCI, adherence to CPAP has shown to improve microvascular function. Although no direct evidence is available, individuals with SCI have shown to have a reduction in the frequency of AD when adherent to CPAP suggesting the microvasculature may be a pro-active therapeutic target for AD and OH. Both autonomic dysfunction and SDB are negatively impacted by the lack of motor function following SCI resulting in deconditioning, atrophy of the muscles and vessels, insulin resistance, and reduced metabolic rate. It has been suggested higher CPAP pressure during in-home treatment coupled with increased upper airway resistances are primary physiological barriers to CPAP treatment. Therefore, treatment options that directly improve the blood pressure response to sympathetic activation, upper airway function as well as improve microvascular function are imperative for those with a SCI. The overall goal of the present proposal is to investigate if daily exposure to mild intermittent hypoxia (MIH) can ameliorate autonomic dysfunction in persons with SCI as well as improve mitochondrial and microvascular function. The investigators will recruit individuals with SCI, concurrent SDB, and signs of autonomic dysfunction who will be randomly assign to one of two groups. Treatment will be administered for 8 days over a 2-week period. Both groups will be treated with nightly in-home CPAP over the 8 days. Lastly, individuals will be tested before, and after MIH as well as return to the laboratory 4 weeks later to undergo post-MIH autonomic, cardiovascular, and peripheral muscle function tests. Participants will return 4-weeks later to investigate if there is a sustained impact of therapeutic MIH on autonomic function and SDB. The dissemination of these outcomes could transform the approach to treating autonomic dysfunction and SDB in individuals with SCI. Therefore, this project will determine if MIH combined with CPAP can be used as prophylaxis for autonomic dysfunction in participants with SCI and autonomic dysfunction.
- Conditions
- Spinal Cord Injuries, Autonomic Dysreflexia
- Being tested
- Mild Intermittent Hypoxia, Sham
- Medical subject headings
- Spinal Cord Injuries, Autonomic Dysreflexia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mild Intermittent HypoxiaOther
Participants will breathe 8% oxygen through a non-diffusible bag that is connected to a 5-way stopcock. The inspiration side of the system is then connected to a 2-way non-rebreathing valve which is connected to a pneumotachometer that is connected to a tight fitting facemask. 100% oxygen and carbon dioxide are titrated into the system to ensure the appropriate hypoxic and hypercapnic stimulus is delivered. The investigators will lower oxygen to 55-60 mmHg and maintain end-tidal carbon dioxide 1-3 mmHg above individual baseline values. The protocol starts with 10 minutes of baseline breathing (room air) then followed by 10 more minutes of breathing room air with the additional carbon dioxide. Thereafter, individuals undergo 12 2-minute bouts of hypoxia with 2 minutes of normoxia (room air) interspersed between episodes. The intervention protocol concludes with 20 minutes of monitoring all breathing and cardiovascular measurements.
ShamOther
Participants will breathe 21% oxygen through a non-diffusible bag that is connected to a 5-way stopcock. The inspiration side of the system is then connected to a 2-way non-rebreathing valve which is connected to a pneumotachometer that is connected to a tight fitting facemask. No supplemental oxygen or carbon dioxide will be used during the sham protocol. The protocol starts with 10 minutes of baseline breathing (room air) then followed by 10 more minutes of breathing room air with the additional carbon dioxide. Thereafter, individuals undergo 12 2-minute bouts of hypoxia with 2 minutes of normoxia (room air) interspersed between episodes. The intervention protocol concludes with 20 minutes of monitoring all breathing and cardiovascular measurements.
| Study group | Role | What they receive |
|---|---|---|
| Mild Intermittent Hypoxia | Experimental | This arm of the protocol will receive mild intermittent hypoxia (8% oxygen) with end-tidal carbon dioxide maintained 1-3 millimeters of mercury above baseline, while in the laboratory. If diagnosed with sleep apnea, participants will be treated with continuous positive airway pressure for the duration of the intervention. Receives: Other: Mild Intermittent Hypoxia |
| Sham | Sham comparator | This arm of the protocol will receive sham air (21% oxygen) while in the laboratory. No additional gases will be employed. If diagnosed with sleep apnea, participants will be treated with continuous positive airway pressure for the duration of the intervention. Receives: Other: Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
Autonomic Dysreflexia
Change in systolic blood pressure during thigh occlusion test.
Measured: 6 minutes, Pre-Intervention, 1 Day after intervention (i.e. post intervention)
Secondary outcomes (1)
Orthostatic Hypotension
The change in systolic blood pressure following positional change (supine to seated)
Measured: 6 minutes, Pre-Intervention, 1 Day after intervention (i.e. post intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2022
- Study start1 Oct 2022
- Primary completion29 Oct 2027 (estimated)
- Study completion29 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Spinal Cord InjuriesStudies 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
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- John D. Dingell VA Medical Center
- Responsible party
- Sponsor
- Investigators
- Gino Panza, PhD, Principal investigator, John D. Dingell VA Medical Center, Detroit, MI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05351827
- Sponsor's protocol ID
- B3847-W
- Other IDs
- IRB-22-04-4550
- Acronym
- MIH and AD
- Status last verified
- Aug 2026
- First submitted
- 18 Apr 2022
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Soltesz AE, Zhao F, Wecht JM, Mateika JH, Panza GS. Mild intermittent hypoxia may improve autonomic dysfunction in persons living with spinal cord injury: a preliminary snapshot. Front Neurosci. 2025 Jul 22;19:1600772. doi: 10.3389/fnins.2025.1600772. eCollection 2025.
PubMed 40766908
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mild Intermittent Hypoxia: A Prophylactic for Autonomic Dysfunction in Individuals With Spinal Cord Injuries
- ClinicalTrials.gov ID
- NCT05351827
- Acronym / sponsor ID
- MIH and AD / B3847-W
- Conditions
- Spinal Cord Injuries, Autonomic Dysreflexia
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- John D. Dingell VA Medical Center
- Study start
- 1 Oct 2022 (actual)
- Primary completion
- 29 Oct 2027 (estimated)
- Study completion
- 29 Oct 2027 (estimated)
- First posted
- 28 Apr 2022 (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.
The prevalence of autonomic dysfunction and sleep disordered breathing (SDB) is increased in individuals with spinal cord injury (SCI). The loss of autonomic control results in autonomic dysreflexia (AD) and orthostatic hypotension (OH) which explains the increase in cardiovascular related mortality in these Veterans. There is no effective prophylaxis for autonomic dysfunction. The lack of prophylactic treatment for autonomic dysfunction, and no best clinical practices for SDB in SCI, are significant health concerns for Veterans with SCI. Therefore, the investigators will investigate the effectiveness of mild intermittent hypoxia (MIH) as a prophylactic for autonomic dysfunction in patients with SCI. The investigators propose that MIH targets several mechanisms associated with autonomic control and the co-morbidities associated with SDB. Specifically, exposure to MIH will promote restoration of homeostatic BP control, which would be beneficial to participation in daily activities and independence in those with SCI.
Detailed description
Individuals with a spinal cord injury (SCI) above the 6th thoracic vertebrae experience severe autonomic dysfunction. These individuals lose the ability to control blood pressure (BP) during a noxious or non-noxious stimulus below the injury (Autonomic Dysreflexia [AD]) and during positional changes (Orthostatic Hypotension [OH]). The loss of descending autonomic control and subsequent loss of BP control are highly prevalent in individuals with SCI. More importantly, many individuals are unaware of the loss of BP control as most individuals remain asymptomatic. These potentially life-threatening oscillations in BP are known to induce further damage; creating a vicious cycle of continued autonomic and cardiovascular dysfunction which explains the increased cardiovascular related mortality. Unfortunately, there is no effect prophylaxis for autonomic dysfunction in these individuals. Furthermore, the prevalence of sleep disordered breathing (SDB) is high in individuals with SCI (tetraplegia can exceed 90%), and there is no current best clinical practice guidelines for treating SDB in individuals with SCI. The primary treatment is with continuous positive airway pressure (CPAP). Unfortunately, treatment adherence remains poor. Moreover, SDB is known to negatively impact autonomic, cardiovascular, and microvascular function in individuals without SCI. In individuals without an SCI, adherence to CPAP has shown to improve microvascular function. Although no direct evidence is available, individuals with SCI have shown to have a reduction in the frequency of AD when adherent to CPAP suggesting the microvasculature may be a pro-active therapeutic target for AD and OH. Both autonomic dysfunction and SDB are negatively impacted by the lack of motor function following SCI resulting in deconditioning, atrophy of the muscles and vessels, insulin resistance, and reduced metabolic rate. It has been suggested higher CPAP pressure during in-home treatment coupled with increased upper airway resistances are primary physiological barriers to CPAP treatment. Therefore, treatment options that directly improve the blood pressure response to sympathetic activation, upper airway function as well as improve microvascular function are imperative for those with a SCI. The overall goal of the present proposal is to investigate if daily exposure to mild intermittent hypoxia (MIH) can ameliorate autonomic dysfunction in persons with SCI as well as improve mitochondrial and microvascular function. The investigators will recruit individuals with SCI, concurrent SDB, and signs of autonomic dysfunction who will be randomly assign to one of two groups. Treatment will be administered for 8 days over a 2-week period. Both groups will be treated with nightly in-home CPAP over the 8 days. Lastly, individuals will be tested before, and after MIH as well as return to the laboratory 4 weeks later to undergo post-MIH autonomic, cardiovascular, and peripheral muscle function tests. Participants will return 4-weeks later to investigate if there is a sustained impact of therapeutic MIH on autonomic function and SDB. The dissemination of these outcomes could transform the approach to treating autonomic dysfunction and SDB in individuals with SCI. Therefore, this project will determine if MIH combined with CPAP can be used as prophylaxis for autonomic dysfunction in participants with SCI and autonomic dysfunction.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mild Intermittent Hypoxia | Experimental | Other: Mild Intermittent HypoxiaThis arm of the protocol will receive mild intermittent hypoxia (8% oxygen) with end-tidal carbon dioxide maintained 1-3 millimeters of mercury above baseline, while in the laboratory. If diagnosed with sleep apnea, participants will be treated with continuous positive airway pressure for the duration of the intervention. |
| Sham | Sham comparator | Other: ShamThis arm of the protocol will receive sham air (21% oxygen) while in the laboratory. No additional gases will be employed. If diagnosed with sleep apnea, participants will be treated with continuous positive airway pressure for the duration of the intervention. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Motor incomplete spinal cord injury at or above the 12th thoracic vertebrae
- Signs or symptoms of autonomic dysfunction (this will be determined by the Autonomic Dysfunction Following Spinal Cord Injury (ADFSCI) and ISAFSCI questions. The ADFSCI requires a score of 1 on questions 16 and 22, and the International Standards to document Autonomic Function following SCI (ISAFSCI) requires a score of 1 on any parameter)
- Chronic injuries (>1 year post injury)
Key exclusion criteria (8 listed)
- Pregnant
- Smoker
- Drug addiction
- Complete spinal cord injury
- Spinal cord injury below the 6th thoracic vertebrae
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 |
|---|---|---|
| Mild Intermittent HypoxiaParticipants will breathe 8% oxygen through a non-diffusible bag that is connected to a 5-way stopcock. The inspiration side of the system is then connected to a 2-way non-rebreathing valve which is connected to a pneumotachometer that is connected to a tight fitting facemask. 100% oxygen and carbon dioxide are titrated into the system to ensure the appropriate hypoxic and hypercapnic stimulus is delivered. The investigators will lower oxygen to 55-60 mmHg and maintain end-tidal carbon dioxide 1-3 mmHg above individual baseline values. The protocol starts with 10 minutes of baseline breathing (room air) then followed by 10 more minutes of breathing room air with the additional carbon dioxide. Thereafter, individuals undergo 12 2-minute bouts of hypoxia with 2 minutes of normoxia (room air) interspersed between episodes. The intervention protocol concludes with 20 minutes of monitoring all breathing and cardiovascular measurements. | Other | Mild Intermittent Hypoxia |
| ShamParticipants will breathe 21% oxygen through a non-diffusible bag that is connected to a 5-way stopcock. The inspiration side of the system is then connected to a 2-way non-rebreathing valve which is connected to a pneumotachometer that is connected to a tight fitting facemask. No supplemental oxygen or carbon dioxide will be used during the sham protocol. The protocol starts with 10 minutes of baseline breathing (room air) then followed by 10 more minutes of breathing room air with the additional carbon dioxide. Thereafter, individuals undergo 12 2-minute bouts of hypoxia with 2 minutes of normoxia (room air) interspersed between episodes. The intervention protocol concludes with 20 minutes of monitoring all breathing and cardiovascular measurements. | Other | Sham |
Primary outcome
Autonomic Dysreflexia
Time frame: 6 minutes, Pre-Intervention, 1 Day after intervention (i.e. post intervention)
Change in systolic blood pressure during thigh occlusion test.
1 secondary outcome
Orthostatic Hypotension
Time frame: 6 minutes, Pre-Intervention, 1 Day after intervention (i.e. post intervention)
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 14 Aug 2026.
- Derived from this study: PubMed 40766908Soltesz AE, Zhao F, Wecht JM, Mateika JH, Panza GS. Mild intermittent hypoxia may improve autonomic dysfunction in persons living with spinal cord injury: a preliminary snapshot. Front Neurosci. 2025 Jul 22;19:1600772. doi: 10.3389/fnins.2025.1600772. eCollection 2025.
- Individual participant dataSharing planned: No
Related trials for Spinal Cord Injuries
Recruiting
Implant for Walking After Incomplete SCI
Spinal Cord Injury (SCI), Gait
Recruiting
MindEx: A Novel, Multifocal, Cognitive Brain-Machine Interface System
Paralysis; Quadriplegic, Quadraplegia
Recruiting
tSCS Combined With Rehabilitation Training in Treating Paraplegic Patients After SCI
Spinal Cord Injury, Paraplegia, Spinal
Active, not recruitingObservational study
Natural History of Shoulder Pathology in Manual Wheelchair Users
Paraplegia, Spinal Cord Injuries
Recruiting
Neuromodulation for Metabolic Dysfunction
Spinal Cord Injuries (SCI), Prediabetes / Type 2 Diabetes
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.
Gino Panza, PhD principal investigator
John D. Dingell VA Medical Center, Detroit, MI
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mild Intermittent Hypoxia in people with Spinal Cord Injuries and Autonomic Dysreflexia, 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 3 inclusion and 8 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 14 Aug 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?
Contact Gino Panza, PhD ((313) 576-1000 ext. 64414, Gino.Panza@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Autonomic Dysreflexia (time frame: 6 minutes, Pre-Intervention, 1 Day after intervention (i.e. post intervention)). 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 NCT05351827, which also lists 1 linked publication.
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 14 Aug 2026.