Recruiting
Phase 1
Phase 2

Intermittent Hypoxia

Sponsor:

VA Office of Research and Development

Code:

NCT05558501

Conditions

Obstructive Sleep Apnea

Eligibility Criteria

Sex: All

Age: 30 - 60

Healthy Volunteers: Not accepted

Interventions

Mild Intermittent Hypoxia

Sham MIH

Study Details

Brief 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

Study ID

NCT05558501

Start date

Jan 1, 2023

Status verified date

Dec, 2025

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 30 - 60

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Male or female of any race, 30-60 years of age with a BMI of less than 40 kg/m2 and a weight to hip ratio of less than 1.3in males and 1.2 in females along with pure or predominantly (i.e., comprised of both a central and obstructive component)OSA (AHI less than or equal to 100 events per hour and an average oxygen desaturation level of 85 % or greater).
  • Participants will be newly diagnosed and not previously treated with CPAP.
  • Participants will also be diagnosed with hypertension. Participants will either be untreated or will be treated unsuccessfully with a single prescribed medication for hypertension. Hypertension will be classified according to the American Heart Association 2018 criteria which includes an elevated systolic blood pressure in the range of 120-129 and a diastolic pressure less than 80 mmHg in addition to stage I and stage II hypertension defined by a systolic blood pressure greater than 130 mmHg and a diastolic pressure greater than 80 mmHg.
  • Participants will also be included if they are pre-diabetic (HbA1C: 5.7 - 6.4 %; fasting blood glucose: 100 - 125 mg/dL) and have cholesterol levels ranging from 200-239 mg/dL.
  • All participants will have normal lung function and a normal EKG with no or minimal alcohol consumption (< 2 oz of alcohol/night).
  • Females will be studied at similar points in their menstrual cycle.

Exclusion Criteria:

  • Participants with baseline blood pressure greater than 160/110 will be excluded from participation.
  • Participants on any medications, with the exception of a single prescribed medication for individuals with resistant hypertension.
  • Participants with any other known disease (e.g. pulmonary hypertension).
  • Participants using any sleep promoting supplements including melatonin.
  • Night shift workers or participants who recently travelled across time zones.
  • Pregnant females.

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Mild Intermittent Hypoxia (MIH)

This arm of the protocol will receive mild intermittent hypoxia (8% oxygen) with end-tidal carbon dioxide maintained 2 millimeters of mercury above baseline, while in the laboratory.

sham comparator: Sham Mild Intermittent Hypoxia (Sham MIH)

This arm of the protocol will receive sham MIH (the equivalent of room air), while in the laboratory.

Interventions

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.

Sham MIH

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

Primary outcome measure

  • Change in Blood Pressure [ Time Frame: Change at 15 days, 4 and 8- weeks following treatment compared to baseline ]
  • Change in Microvascular Function (Maximal hyperemic Response) [ Time Frame: Change at 15 days, 4 and 8- weeks following treatment compared to baseline ]
  • Change in Microvascular Function (Time to reach Maximal Hyperemic Response) [ Time Frame: Change at 15 days, 4 and 8- weeks following treatment compared to baseline ]

Central Contacts and Locations

Central contacts

Jason H Mateika, PhD MS BS

(313) 576-4481jmateika@med.wayne.edu

Shipra Puri

(313) 576-1000shiprapuri@wayne.edu

Locations

John D. Dingell VA Medical Center, Detroit, MI

Recruiting

Detroit, Michigan, United States, 48201-1916

Contacts

Edi Levi, MD

313-576-4451edi.levi@va.gov

Erin Olgren, PhD MS

(313) 576-4448erin.olgren@va.gov

Principal Investigator:

Jason H Mateika, PhD MS BS

More Information

Sponsor

VA Office of Research and Development

Last update posted

Dec 4, 2025

Last verified

Dec, 2025

Keywords

  • Intermittent Hypoxia
  • Microvascular Function
  • Fatigability
  • Maximal Oxygen Consumption
  • Sympatho-Vagal Balance
  • CPAP Adherence
  • Arousal Threshold

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2025-12-04.