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

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-60
SponsorVA Office of Research and Development

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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)

Disqualifiers

Pregnant

Smoker

Drug addiction

Complete spinal cord injury

Trial design

Design model

Parallel

Treatments tested in this trial

  • Mild Intermittent Hypoxia

    Other intervention

    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.

  • Sham

    Other intervention

    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.

Treatment groups

24 Participants
are divided into 2 treatment groups
Group A: Mild Intermittent HypoxiaExperimental treatment 1 intervention
Group B: ShamSham comparator 1 intervention

Trial outcomes

Primary outcomes

1

Autonomic Dysreflexia

Change in systolic blood pressure during thigh occlusion test.

Time frame
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)

Time frame
6 minutes, Pre-Intervention, 1 Day after intervention (i.e. post intervention)

Other outcomes

1

Mitochondrial Capacity

Oxygen consumption during thigh occlusion

Time frame
6 minutes, Pre-Intervention, 1 Day after intervention (i.e. post intervention)
2

Microvascular function

Maximum hyperemic response following 6-minute occlusion test

Time frame
6 minutes, Pre-Intervention, 1 Day after intervention (i.e. post intervention)

Sponsors and contacts

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VA Office of Research and Development

Lead sponsor

John D. Dingell VA Medical Center

Collaborator