Mild Intermittent Hypoxia: A Prophylactic for Autonomic Dysfunction in Individuals With Spinal Cord Injuries

NCT05351827 | Recruiting DMC

• 2 other identifiers: B3847-WIRB-22-04-4550
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Spinal Cord Injuries; Autonomic Dysreflexia

Outcome Measures

Primary Outcomes (1)

• Autonomic Dysreflexia

  Change in systolic blood pressure during dual-thigh occlusion test.

  6 minutes, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention

Secondary Outcomes (1)

• Orthostatic Hypotension

  15 minutes, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention

Other Outcomes (2)

• Mitochondrial Capacity

  6 minutes, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention

• Microvascular function

  6 minutes, Pre-Intervention, 1 Day after intervention, 2 weeks after intervention

Study Arms (2)

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.

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.

Other: Sham

Interventions

Mild Intermittent Hypoxia OTHER

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.

Mild Intermittent Hypoxia

Sham OTHER

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.

Sham

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-60
• Motor incomplete spinal cord injury at or above the 12th 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead
• John D. Dingell VA Medical Center: collaborator

Study Sites (1)

John D. Dingell VA Medical Center, Detroit, MI

Detroit, Michigan, 48201-1916, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 40766908 DERIVED

MeSH Terms

Conditions

Spinal Cord Injuries; Autonomic Dysreflexia

Interventions

salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Autonomic Nervous System Diseases

Study Officials

• Gino Panza, PhD

  John D. Dingell VA Medical Center, Detroit, MI

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gino Panza, PhD

CONTACT

(313) 576-1000; Gino.Panza@va.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2022
• First Posted: April 28, 2022
• Study Start: October 1, 2022
• Primary Completion (Estimated): October 29, 2026
• Study Completion (Estimated): October 29, 2026
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)