Intermittent Hypoxia-initiated Plasticity in Humans: A Multi-pronged Therapeutic Approach to Treat Sleep Apnea and Overlapping Co-morbidities

Summary

The prevalence of obstructive sleep apnea (OSA) is high in the United States and is a major health concern. This disorder is linked to numerous heart, blood vessel and nervous system abnormalities, along with increased tiredness while performing exercise likely because of a reduced blood supply to skeletal muscles. The gold standard treatment of OSA with continuous positive airway pressure (CPAP) in many cases does not lead to significant improvements in health outcomes because the recommended number of hours of treatment per night is often not achieved. Thus, development of novel treatments to eliminate apnea and lessen the occurrence of associated health conditions is important. The investigators will address this mandate by determining if repeated exposure to mild intermittent hypoxia (MIH) reduces heart and blood vessel dysfunction and tiredness/ fatigue experienced while exercise performance. The investigators propose that exposure to MIH has a multipart effect. MIH directly targets heart and blood vessel associated conditions, while simultaneously increasing upper airway stability and improving sleep quality. These modifications may serve to directly decrease breathing episodes and may also serve to improve usage of CPAP. Independent of its effect, MIH may serve as an adjunctive therapy which provides another path to reducing heart and blood vessel abnormalities that might ultimately result in improvements in exercise capacity and reverse performance fatigue in individuals with OSA.

Conditions

• Obstructive Sleep Apnea

Interventions

OTHER

Mild Intermittent Hypoxia

The MIH protocol will be comprised of a 20-minute baseline period followed by exposure to twelve two-minute episodes of hypoxia \[partial pressure of end-tidal oxygen (PETO2)= 50 mmHg\]. Each episode will be interspersed with a 2-minute recovery period under normoxic conditions. The final episode will be followed by a 30-minute end-recovery period. The partial pressure of end-tidal carbon dioxide (PETCO2) will be sustained 2 mmHg above baseline values for the last ten minutes of baseline and throughout the remainder of the protocol. To rapidly induce a PETO2 of 50 mmHg participants will inspire a gas mixture comprised of 8 % oxygen and 92 % nitrogen from a non-diffusible bag. To maintain PETO2 (i.e. 50 mmHg) and PETCO2 (i.e. 2 mmHg above baseline) at the desired levels supplemental oxygen and carbon dioxide will be added to the inspiratory line from the output of a flow meter device that receives inputs from tanks of 100 % oxygen and 100 % carbon dioxide.

OTHER

Sham MIH

During "sham MIH" the participants will be exposed to compressed air (the equivalent of room air).

Sponsors & Collaborators

• John D. Dingell VA Medical Center

  collaborator FED

• VA Office of Research and Development

  lead FED

Principal Investigators

• Jason H Mateika, PhD MS BS · John D. Dingell VA Medical Center, Detroit, MI

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

30 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-01-01

Primary Completion

2026-12-31

Completion

2027-12-31

Countries

• United States

Study Locations