[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT05351827":3,"trial-entities:NCT05351827":100,"trial-summary:NCT05351827":105},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":6,"overall_status":7,"completion_date":8,"status_verified_date":9,"last_update_date":10,"start_date":11,"sponsor_name":12,"lead_sponsor_class":13,"has_dmc":14,"brief_summary":15,"detailed_description":16,"conditions":17,"keywords":20,"study_type":21,"primary_purpose":22,"phases":23,"enrollment_info":25,"interventions":28,"primary_outcomes":38,"secondary_outcomes":42,"sex":46,"minimum_age":47,"maximum_age":48,"healthy_volunteers":49,"eligibility_criteria":50,"std_ages":65,"locations":67,"central_contacts":90,"overall_officials":92,"references":94,"see_also_links":99},"NCT05351827","B3847-W","Mild Intermittent Hypoxia: A Prophylactic for Autonomic Dysfunction in Individuals With Spinal Cord Injuries","RECRUITING","2027-10-29","2026-08","2026-08-14","2022-10-01","VA Office of Research and Development","FED",true,"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.","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.",[18,19],"Spinal Cord Injuries","Autonomic Dysreflexia",[],"INTERVENTIONAL","TREATMENT",[24],"NA",{"count":26,"type":27},24,"ESTIMATED",[29,34],{"type":30,"name":31,"description":32,"armGroupLabels":33},"OTHER","Mild Intermittent Hypoxia","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.",[31],{"type":30,"name":35,"description":36,"armGroupLabels":37},"Sham","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.",[35],[39],{"measure":19,"description":40,"timeFrame":41},"Change in systolic blood pressure during thigh occlusion test.","6 minutes, Pre-Intervention, 1 Day after intervention (i.e. post intervention)",[43],{"measure":44,"description":45,"timeFrame":41},"Orthostatic Hypotension","The change in systolic blood pressure following positional change (supine to seated)","ALL","18 Years","60 Years",false,{"inclusion":51,"exclusion":55,"raw_text":64},[52,53,54],"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)",[56,57,58,59,60,61,62,63],"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","Inclusion Criteria:\n\n* Motor incomplete spinal cord injury at or above the 12th thoracic vertebrae\n* 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)\n* Chronic injuries (\\>1 year post injury)\n\nExclusion Criteria:\n\n* Pregnant\n* Smoker\n* Drug addiction\n* Complete spinal cord injury\n* Spinal cord injury below the 6th thoracic vertebrae\n* Insulin dependent diabetes\n* Shift workers (i.e., disrupted circadian rhythm)\n* Active skin breakdown or pressure sores",[66],"ADULT",[68],{"facility":69,"status":7,"city":70,"state":71,"zip":72,"country":73,"contacts":74,"geoPoint":87},"John D. Dingell VA Medical Center, Detroit, MI","Detroit","Michigan","48201-1916","United States",[75,81,85],{"name":76,"role":77,"phone":78,"phoneExt":79,"email":80},"Gino Panza, PhD","CONTACT","(313) 576-1000","64414","Gino.Panza@va.gov",{"name":82,"role":77,"phone":83,"email":84},"Erin Olgren, PhD MS","(313) 576-4448","erin.olgren@va.gov",{"name":76,"role":86},"PRINCIPAL_INVESTIGATOR",{"lat":88,"lon":89},42.33143,-83.04575,[91],{"name":76,"role":77,"phone":78,"phoneExt":79,"email":80},[93],{"name":76,"affiliation":69,"role":86},[95],{"pmid":96,"type":97,"citation":98},"40766908","DERIVED","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\u002Ffnins.2025.1600772. eCollection 2025.",[],{"nct_id":4,"conditions":101,"biomarkers":104},[102,103],"Autonomic dysreflexia","Spinal Cord Injury",[],{"nct_id":4,"found":14,"summary":106,"prompt_version":116},{"design":107,"status":108,"heading":109,"summary":110,"follow_up":111,"word_count":112,"commitments":113,"compensation":114,"drugs_mentioned":115},"This is an interventional study, meaning participants will receive a specific treatment. It plans to enroll 24 participants, but the specific design (like if it's randomized or blinded) is not specified.","completed","Mild Intermittent Hypoxia for Autonomic Dysfunction in Spinal Cord Injuries","This study is investigating if breathing \"Mild Intermittent Hypoxia\" (air with less oxygen) can help prevent autonomic dysfunction in people with spinal cord injuries. Autonomic dysfunction can cause problems like Autonomic Dysreflexia (sudden, dangerous high blood pressure) and Orthostatic Hypotension (low blood pressure when standing up). Currently, there isn't an effective way to prevent these issues. You might be able to join if you are 18-60 years old, have an incomplete spinal cord injury at or above the T12 level, and show signs of autonomic dysfunction. The researchers will measure Autonomic Dysreflexia at different times: before the intervention, 6 minutes after, 1 day after, and 2 weeks after. The study status is unclear and plans to enroll 24 participants.","Participants will be followed for up to 2 weeks after the intervention to measure Autonomic Dysreflexia.",119,"Participants will breathe either 8% oxygen (Mild Intermittent Hypoxia) or 21% oxygen (Sham) through a facemask system. The duration or frequency of these sessions is not detailed.","Not stated in the trial record.",[31],"v2"]