# Mild intermittent hypoxia:  A therapeutic modality to mitigate co-morbidities and promote recovery of respiratory motor function in spinal cord injured patients with sleep apnea

> **NIH VA IK1** · JOHN D DINGELL VA MEDICAL CENTER · 2021 · —

## Abstract

The prevalence of obstructive sleep apnea (OSA) is high in Veterans with an intact spinal cord99 and the
prevalence is even greater (i.e.74%) in patients with tetraplegia19. Incomplete spinal cord injury (SCI) with
concurrent OSA is accompanied by autonomic, cardiovascular and neurocognitive co-morbidities, as well as,
respiratory and limb motor dysfunction. Treatment options to mitigate these co-morbidities while promoting
recovery of respiratory motor function range from limited to non-existent96. The overall goal of the present
proposal is to investigate if daily exposure to mild intermittent hypoxia (MIH) [can increase upper airway
muscle activity leading to increased nightly in-home] continuous positive airway pressure [(CPAP) usage
(Hours/night). The direct effects of MIH in combination with the improved nightly in-home CPAP] can serve as
a multipronged therapeutic approach to mitigate autonomic, cardiovascular and neurocognitive co-morbidities
while promoting recovery of respiratory motor function in individuals suffering from SCI and concurrent OSA.
We believe that exposure to daily MIH could reduce the positive pressure required to treat sleep apnea at
home and as a result could improve in-home treatment adherence. Improved adherence could contribute to
mitigating the co-morbidities listed above. In addition, MIH might also directly impact these co-morbidities while
promoting recovery of respiratory neuromuscular function. To accomplish our goal we will recruit individuals
with SCI and concurrent OSA, and randomly assign them to one of two groups. [The participants will be
blinded to group assignment]. One group will be treated daily with MIH for a period of 15 days over a 3 week
period (i.e. 5 days/week) and the other group will be exposed to ambient air (i.e. control group). In addition,
both groups will be treated with [nightly in-home] CPAP over the length of the protocol. At the beginning,
middle and end of the protocol a number of measures will be obtained to assess if exposure to MIH can
effectively mitigate the co-morbidities listed above, [as well as reduce the therapeutic pressure required to
treat] OSA. Blood pressure is a primary outcome and will be measured over a 24 hour period with an
ambulatory automated BP monitoring device before and after the protocol. Additionally, automated and manual
measures of BP will be obtained before, during, and after MIH treatment sessions. Neurocognitive function at
the beginning and end of the protocol will be assessed using tests that focus on vigilance, memory and
executive function. Autonomic function will be assessed on a day to day basis during therapy via heart rate and
BP variability analysis. The therapeutic CPAP pressure, and active and passive critical closing pressure of the
upper airway will be measured at the beginning, middle and end of the protocol. [Additionally, carbon dioxide
retention will be measured daily during the first 10 minutes of each visit by monitoring end tidal...

## Key facts

- **NIH application ID:** 10421046
- **Project number:** 5IK1RX002945-03
- **Recipient organization:** JOHN D DINGELL VA MEDICAL CENTER
- **Principal Investigator:** Gino S Panza
- **Activity code:** IK1 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-11-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10421046

## Citation

> US National Institutes of Health, RePORTER application 10421046, Mild intermittent hypoxia:  A therapeutic modality to mitigate co-morbidities and promote recovery of respiratory motor function in spinal cord injured patients with sleep apnea (5IK1RX002945-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10421046. Licensed CC0.

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