NCT05558501 · VA Office of Research and Development
Intermittent Hypoxia-initiated Plasticity in Humans: A Multi-pronged Therapeutic Approach to Treat Sleep Apnea and Overlapping Co-morbidities
What this study is about
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.
View original scientific description
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.
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).
Primary outcome measures
Change in Blood Pressure
Time frame: Change at 15 days, 4 and 8- weeks following treatment compared to baseline
Blood pressure measures over 24 hours will be obtained. Blood pressure will be measured every 20 minutes beginning on Sunday at 6 AM and ending Monday at 6 AM. Participants will wear an actigraph (Actiwatch Spectrum, Respironics) and record their activities in a journal to determine the arousal state (i.e., active wakefulness, quiet wakefulness and sleep) associated with each blood pressure measurement. The data will be separated into active-awake, rest-awake and sleep based on the activity log and corresponding data from an actigraph watch. The average value of blood pressure in a healthy individual is 120/80 mmHg. In their participants with OSA, the investigators expect the blood pressure to be higher at baseline and decrease 15 days after treatment. The investigators also expect that this reduction will be maintained at 4 and 8-weeks following treatment.
Change in Microvascular Function (Maximal hyperemic Response)
Time frame: Change at 15 days, 4 and 8- weeks following treatment compared to baseline
Microvascular reactivity associated with hyperemia induced by vascular occlusion will be determined by analyzing the maximal hyperemic response (MHR) of tissue saturation index (TSI) signal derived from near-infrared spectroscopy (NIRS) of the lateral gastrocnemius muscle of the non-dominant leg. The average value of TSI MHR of the NIRS signals in healthy individuals is 159±9 %. In their participants with OSA, the investigators expect these values to be lower at baseline and to increase 15 days after treatment. The investigators also expect that the increase will be maintained 4 and 8-weeks following treatment.
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
Microvascular reactivity associated with hyperemia induced by vascular occlusion will be determined by analyzing the time to reach maximal hyperemic response (tM) of tissue saturation index (TSI) signal derived from near-infrared spectroscopy (NIRS) of the lateral gastrocnemius muscle of the non-dominant leg. The average value of tM TSI in healthy individuals is 39±5 s. In their participants with OSA, the investigators expect these values to be higher at baseline and to lower 15 days after treatment. The investigators also expect that the decrease will be maintained 4 and 8-weeks following treatment.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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.
Where
- Detroit, Michigan
Collaborators
John D. Dingell VA Medical Center
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Dec 4, 2025 · Source of record for eligibility and locations