- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05351827
Mild Intermittent Hypoxia: A Prophylactic for Autonomic Dysfunction in Individuals With Spinal Cord Injuries (MIH and AD)
October 3, 2023 updated by: VA Office of Research and Development
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Estimated)
24
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Gino Panza, PhD
- Phone Number: 64414 (313) 576-1000
- Email: Gino.Panza@va.gov
Study Locations
-
-
Michigan
-
Detroit, Michigan, United States, 48201-1916
- Recruiting
- John D. Dingell VA Medical Center, Detroit, MI
-
Contact:
- Gino Panza, PhD
- Phone Number: 64414 313-576-1000
- Email: Gino.Panza@va.gov
-
Principal Investigator:
- Gino Panza, PhD
-
Contact:
- Erin Olgren, PhD MS
- Phone Number: (313) 576-4448
- Email: erin.olgren@va.gov
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 60 years (Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Age 18-60
- Motor incomplete spinal cord injury at or above the 6th thoracic vertebrae
- Signs or symptoms of autonomic dysfunction (this will be determined by the ADFSCI and ISAFSCI questions. The ADFSCI requires a score of 1 on questions 16 and 22, and the ISAFSCI requires a score of 1 on any parameter)
- Chronic injuries (> 1 year post injury)
Exclusion Criteria:
- Pregnant
- Smoker
- Drug addiction
- <18 or >60 years of age
- Complete spinal cord injury
- Spinal cord injury below the 6th thoracic vertebrae
- Insulin dependent diabetes
- Shift workers (ie disrupted circadian rhythm)
- Active skin breakdown or pressure sores
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Mild Intermittent Hypoxia
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.
|
Participants will breathe 8% oxygen through a non-diffusable 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.
|
Sham Comparator: Sham
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.
|
Participants will breathe 21% oxygen through a non-diffusable 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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Autonomic Dysreflexia
Time Frame: 6 minutes, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention
|
Change in systolic blood pressure during dual-thigh occlusion test.
|
6 minutes, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
24-hour blood pressure variability
Time Frame: 24-hours, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention
|
Brachial systolic blood pressure fluctuations greater than 20 mmHg above baseline and 10 mmHg below baseline.
|
24-hours, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention
|
Orthostatic Hypotension
Time Frame: 15 minutes, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention
|
The change in systolic blood pressure following positional change (supine to seated)
|
15 minutes, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention
|
Spinal Cord Independence Measure (SCIM III)
Time Frame: Pre-Intervention, 1 Day after intervention, 2 weeks after intervention
|
Survey
|
Pre-Intervention, 1 Day after intervention, 2 weeks after intervention
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mitochondrial Capacity
Time Frame: 6 minutes, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention
|
Oxygen consumption during thigh occlusion
|
6 minutes, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention
|
Microvascular function
Time Frame: 6 minutes, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention
|
Maximum hyperemic response following 6-minute occlusion test
|
6 minutes, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention
|
Cardiac Function
Time Frame: Pre-Intervention, 1 Day after intervention, 2 weeks after intervention
|
Echocardiograms.
The primary measure is left ventricular stroke volume.
|
Pre-Intervention, 1 Day after intervention, 2 weeks after intervention
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Gino Panza, PhD, John D. Dingell VA Medical Center, Detroit, MI
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 1, 2022
Primary Completion (Estimated)
October 29, 2026
Study Completion (Estimated)
October 29, 2026
Study Registration Dates
First Submitted
April 18, 2022
First Submitted That Met QC Criteria
April 22, 2022
First Posted (Actual)
April 28, 2022
Study Record Updates
Last Update Posted (Actual)
October 4, 2023
Last Update Submitted That Met QC Criteria
October 3, 2023
Last Verified
October 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- B3847-W
- IRB-22-04-4550 (Other Identifier: John D. Dingell VA Medical Center)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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