Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Mild Intermittent Hypoxia: A Prophylactic for Autonomic Dysfunction in Individuals With Spinal Cord Injuries (MIH and AD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05351827
Recruitment Status : Not yet recruiting
First Posted : April 28, 2022
Last Update Posted : June 16, 2022
Sponsor:
Collaborator:
John D. Dingell VA Medical Center
Information provided by (Responsible Party):
VA Office of Research and Development

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Spinal Cord Injuries Autonomic Dysreflexia Other: Mild Intermittent Hypoxia Other: Sham Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Mild Intermittent Hypoxia: A Prophylactic for Autonomic Dysfunction in Individuals With Spinal Cord Injuries
Estimated Study Start Date : October 1, 2022
Estimated Primary Completion Date : October 29, 2026
Estimated Study Completion Date : October 29, 2026

Resource links provided by the National Library of Medicine


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.
Other: Mild Intermittent Hypoxia
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.
Other: Sham
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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)

  3. Spinal Cord Independence Measure (SCIM III) [ Time Frame: Pre-Intervention, 1 Day after intervention, 2 weeks after intervention ]
    Survey


Other Outcome Measures:
  1. Mitochondrial Capacity [ Time Frame: 6 minutes, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention ]
    Oxygen consumption during thigh occlusion

  2. Microvascular function [ Time Frame: 6 minutes, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention ]
    Maximum hyperemic response following 6-minute occlusion test

  3. Cardiac Function [ Time Frame: Pre-Intervention, 1 Day after intervention, 2 weeks after intervention ]
    Echocardiograms. The primary measure is left ventricular stroke volume.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18-60
  2. Motor incomplete spinal cord injury at or above the 6th thoracic vertebrae
  3. 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)
  4. Chronic injuries (> 1 year post injury)

Exclusion Criteria:

  1. Pregnant
  2. Smoker
  3. Drug addiction
  4. <18 or >60 years of age
  5. Complete spinal cord injury
  6. Spinal cord injury below the 6th thoracic vertebrae
  7. Insulin dependent diabetes
  8. Shift workers (ie disrupted circadian rhythm)
  9. Active skin breakdown or pressure sores

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05351827


Contacts
Layout table for location contacts
Contact: Gino Panza, PhD (313) 576-1000 ext 64414 Gino.Panza@va.gov

Locations
Layout table for location information
United States, Michigan
John D. Dingell VA Medical Center, Detroit, MI
Detroit, Michigan, United States, 48201
Contact: Gino Panza, PhD    313-576-1000 ext 64414    Gino.Panza@va.gov   
Contact: Erin Olgren, PhD MS    (313) 576-4448    erin.olgren@va.gov   
Principal Investigator: Gino Panza, PhD         
Sponsors and Collaborators
VA Office of Research and Development
John D. Dingell VA Medical Center
Investigators
Layout table for investigator information
Principal Investigator: Gino Panza, PhD John D. Dingell VA Medical Center, Detroit, MI
Layout table for additonal information
Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT05351827    
Other Study ID Numbers: B3847-W
IRB-22-04-4550 ( Other Identifier: John D. Dingell VA Medical Center )
First Posted: April 28, 2022    Key Record Dates
Last Update Posted: June 16, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Spinal Cord Injuries
Autonomic Nervous System Diseases
Primary Dysautonomias
Autonomic Dysreflexia
Hypoxia
Wounds and Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Signs and Symptoms, Respiratory