Mild Intermittent Hypoxia for Sleep Apnea

Recruiting at 1 trial location

Overseen By Shipra Puri, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Wayne State University

Must not be taking: Blood pressure meds, Melatonin

Disqualifiers: Current CPAP use, Night shift, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: 3 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist people with sleep apnea by using mild intermittent hypoxia (IH) alongside regular CPAP therapy (Continuous Positive Airway Pressure). Researchers believe this combination might enhance CPAP's effectiveness and adherence, potentially reducing sleep apnea's side effects. The trial will also examine the treatment's impact on heart health, metabolism, and brain function. Individuals who might qualify have untreated sleep apnea with frequent breathing disruptions and high blood pressure. Participants will experience mild IH during the day and continue using CPAP at night. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could improve sleep apnea treatment options.

Will I have to stop taking my current medications?

Yes, you will need to stop taking medications for high blood pressure and sleep-promoting supplements like melatonin to participate in this trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that mild intermittent hypoxia (IH) is generally safe. In past studies, those exposed to mild IH experienced benefits such as lower blood pressure and improved blood vessel function. These positive effects appeared in individuals with high blood pressure, even without sleep apnea.

Regarding safety, studies indicate that mild IH can enhance heart and nervous system functions in those with sleep apnea. This suggests it is well-tolerated and may offer several health benefits. Importantly, no serious side effects were reported in the studies reviewed.

Overall, current research suggests that mild IH is a safe and promising method for improving health in individuals with conditions like sleep apnea. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a novel approach to treating sleep apnea using mild intermittent hypoxia (IH) alongside standard CPAP therapy. Unlike traditional treatments that rely solely on CPAP, this method introduces short episodes of reduced oxygen levels during wakefulness, potentially enhancing the body's adaptive responses. The unique aspect of this trial is its focus on the potential cardiovascular benefits of IH, particularly for patients with both sleep apnea and hypertension. This could lead to improved blood pressure regulation and overall cardiovascular health, offering a promising new direction for treatment.

What evidence suggests that this trial's treatments could be effective for sleep apnea?

In this trial, participants in the experimental group will receive mild intermittent hypoxia (IH) alongside CPAP therapy. Research has shown that mild IH can benefit individuals with obstructive sleep apnea (OSA). Specifically, studies have found that mild IH can lower blood pressure in those with high blood pressure and OSA, which may benefit heart health. It can also enhance upper airway function, potentially reducing the need for CPAP machines during sleep. This improvement might make it easier for individuals to continue CPAP treatment. Using mild IH with CPAP could stabilize breathing and enhance heart and metabolic health. These findings suggest that mild IH could be a promising addition to OSA treatment. ^{1 2 3 6 7}

Who Is on the Research Team?

Jason H Mateika, Ph.D.

Principal Investigator

Wayne State University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with a BMI under 40, newly diagnosed sleep apnea, prehypertension or Stage 1 hypertension, and normal lung function. Spinal cord injury patients meeting specific criteria can also join. Exclusions include other diseases besides high blood pressure and sleep apnea, certain medications, effective CPAP users, night shift workers or recent time zone travelers.

Inclusion Criteria

Your body mass index is less than 40.

You have just been diagnosed with sleep apnea and have not started treatment for it.

You have been diagnosed with prehypertension or Stage 1 hypertension according to the American Heart Association.

Exclusion Criteria

You have a medical condition other than high blood pressure and sleep apnea.

You are taking medications for high blood pressure or sleep aids like melatonin.

You use a CPAP machine for at least 4 hours every night.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo mild intermittent hypoxia (IH) protocol during wakefulness for 15 days over a 3-week period, coupled with CPAP treatment during sleep.

3 weeks

Daily sessions for 15 days

Follow-up

Participants are monitored for changes in blood pressure, respiratory function, and other health metrics after treatment.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Continuous positive airway pressure (CPAP)
• Mild intermittent hypoxia
• Sham protocol

Trial Overview The study tests if mild intermittent hypoxia (IH) can serve as an adjunct therapy to improve the effectiveness of CPAP in treating obstructive sleep apnea by increasing upper airway stability and compliance with treatment. It will also assess IH's direct effects on cardiovascular health, metabolism, and neurocognitive functions.

How Is the Trial Designed?

Group I: Experimental Group Experimental Treatment 2 Interventions

The experimental group is comprised of participants with OSA and hypertension \[either able bodied (Aim 1) or with spinal cord injury (Aim 2)\] that will be treated with mild IH and CPAP. In the present proposal, the mild IH protocol will be administered during wakefulness each day for 15 days over a 3-week period to participants that will also be treated with CPAP during sleep. The mild IH 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 PETCO2 will be sustained 2 mmHg above baseline values for the last ten minutes of baseline and throughout the remainder of the protocol.

Group II: Control Group Placebo Group 2 Interventions

The control group is comprised of hypertensive OSA participants \[either able bodied (Aim 1) or with spinal cord injury (Aim 2)\] that will be exposed to a sham protocol in addition to being treated with CPAP during sleep. The sham protocol will be administered during wakefulness for 15 days over a 3-week period. During the sham protocol the participants will be exposed to atmospheric levels of oxygen and carbon dioxide for the duration of the protocol.

Continuous positive airway pressure (CPAP) is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as CPAP for:

• Obstructive Sleep Apnea (OSA)

Approved in United States as CPAP for:

• Obstructive Sleep Apnea (OSA)
• Central Sleep Apnea (CSA)

Approved in Canada as CPAP for:

• Obstructive Sleep Apnea (OSA)

Approved in Japan as CPAP for:

• Obstructive Sleep Apnea (OSA)

Who Is Running the Clinical Trial?

Wayne State University

Lead Sponsor

Trials

318

Recruited

111,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study of 54 patients with sleep apnoea/hypopnoea syndrome, the average nightly usage of CPAP therapy was only 4.7 hours, which is less than the recommended duration for effective treatment.

There was no correlation between the severity of sleep apnoea and the amount of CPAP used, and patients who experienced side effects from the therapy tended to use it significantly less, highlighting the importance of monitoring and addressing side effects to improve compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compliance with CPAP therapy in patients with the sleep apnoea/hypopnoea syndrome. Engleman, HM., Martin, SE., Douglas, NJ.[2019]

In a meta-analysis of 18 studies involving 4146 patients, CPAP therapy did not significantly reduce the risk of cardiovascular events compared to control groups, suggesting its efficacy in this area is unclear.

However, CPAP therapy was associated with significantly lower daytime sleepiness and reduced 24-hour systolic and diastolic blood pressure, indicating potential benefits in improving sleep quality and cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of CPAP therapy on cardiovascular events and mortality in patients with obstructive sleep apnea: a meta-analysis. Guo, J., Sun, Y., Xue, LJ., et al.[2022]

In a study involving 21 patients with obstructive sleep apnea (OSA), the wakefulness promoter modafinil significantly improved driving simulator performance and neurocognitive function during periods of interrupted CPAP therapy.

Modafinil also reduced subjective sleepiness, indicating it can effectively help maintain alertness and performance in patients experiencing declines due to CPAP withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modafinil effects during acute continuous positive airway pressure withdrawal: a randomized crossover double-blind placebo-controlled trial. Williams, SC., Marshall, NS., Kennerson, M., et al.[2018]

In a study involving 98 subjects with obstructive sleep apnoea (OSA), different methods of CPAP pressure delivery (autotitration vs. fixed pressure) showed no significant differences in clinical outcomes after 6 months of treatment.

The findings suggest that the method of determining CPAP pressure does not impact the effectiveness of treatment for OSA, indicating that simpler methods may be just as effective as more complex autotitration systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of three ways to determine and deliver pressure during nasal CPAP therapy for obstructive sleep apnoea. West, SD., Jones, DR., Stradling, JR.[2018]

High flow nasal insufflation (HFNI) was well tolerated by three patients with moderate to severe obstructive sleep apnea (OSA) who struggled with CPAP compliance, showing no significant desaturation episodes postoperatively.

HFNI improved patient comfort compared to CPAP therapy and may provide a beneficial alternative treatment option in the perioperative setting by enhancing airflow and reducing hypopnea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative use of high flow nasal insufflation for obstructive sleep apnea. Gobindram, A., Singh, PA., Quek, KH.[2020]

In a study of 16 patients with mild sleep apnoea/hypopnoea syndrome (SAHS), CPAP treatment led to significant improvements in symptoms, mental flexibility, and depression ratings, indicating its potential benefits even in mild cases.

Despite no significant changes in sleepiness, 10 out of 16 patients preferred CPAP treatment, suggesting that it can enhance quality of life for some individuals with mild SAHS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of CPAP therapy on daytime function in patients with mild sleep apnoea/hypopnoea syndrome. Engleman, HM., Martin, SE., Deary, IJ., et al.[2022]

Exposure to mild intermittent hypoxia significantly reduced the therapeutic continuous positive airway pressure (CPAP) needed to eliminate breathing events in 10 male participants, suggesting a potential improvement in treatment compliance for sleep apnea.

Unlike the sham protocol, which resulted in flow limitation and increased upper airway resistance, the intermittent hypoxia protocol maintained airway stability, indicating that this approach may enhance upper airway muscle activity and provide additional therapeutic benefits for sleep apnea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure to intermittent hypoxia and sustained hypercapnia reduces therapeutic CPAP in participants with obstructive sleep apnea. El-Chami, M., Sudan, S., Lin, HS., et al.[2019]

In a study of 4275 patients with obstructive sleep apnea (OSA), those treated with continuous positive airway pressure (CPAP) showed a lower incidence of stroke (3.41 vs 5.43 per 1000 person-years) compared to those who did not receive CPAP treatment.

While CPAP treatment suggested a protective effect against stroke (hazard ratio of 0.68), the results were not statistically significant, indicating that further research is needed to confirm these findings and assess the quality and duration of CPAP use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous positive pressure therapy usage and incident stroke in patients with obstructive sleep apnea: A nationwide population-based cohort study. Chang, ET., Chen, W., Wang, LY., et al.[2021]

A newly developed telemonitoring system for CPAP therapy was designed through a comprehensive process involving input from sleep specialists, patients, and system developers, aiming to enhance adherence in patients with obstructive sleep apnea (OSA).

Usability tests indicated that while there were some functionality issues reported by users, the system has the potential to improve communication and support for patients, which could lead to better adherence to CPAP therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A telemonitoring system to support CPAP therapy in patients with obstructive sleep apnea: a participatory approach in analysis, design, and evaluation. Aalaei, S., Amini, M., Mazaheri Habibi, MR., et al.[2022]

Continuous positive airway pressure (CPAP) therapy is an effective treatment for obstructive sleep apnea, which can lead to reduced sympathetic nervous system activity and lower blood pressure.

CPAP therapy also improves inflammatory and metabolic parameters, contributing to a decreased risk of cardiovascular issues in patients with obstructive sleep apnea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Beneficial effect of continuous positive airway pressure therapy in obstructive sleep apnea syndrome]. Magyar, MT.[2015]

In a study of 16 patients with mild to moderate obstructive sleep apnea, acute intermittent hypoxia significantly reduced the apnea-hypopnea index by an average of 8.9 events per hour compared to normoxia, indicating its potential efficacy as a treatment.

Acute intermittent hypoxia also led to a significant decrease in the oxygen desaturation index, with 11 out of 16 participants responding positively, suggesting it may be a safe and effective therapeutic approach for managing obstructive sleep apnea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled crossover trial of acute intermittent and continuous hypoxia exposure in mild-moderate obstructive sleep apnea: A feasibility study. Zha, S., Liu, X., Chen, H., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9838631/

Daily Exposure to Mild Intermittent Hypoxia Reduces Blood ... MIH administered during wakefulness has been shown to significantly reduce blood pressure in untreated patients with hypertension without documented sleep apnea ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03736382

Mild Intermittent Hypoxia and Its Multipronged Effect on ... Thus, daily repeated exposure to IH could have significant therapeutic effects on limb motor function in individuals with SCI accompanied by sleep apnea.

3. atsjournals.org atsjournals.org/doi/full/10.1164/rccm.202201-0134LE

Mild Intermittent Hypoxia: A New Treatment Approach for ... Mild intermittent hypoxia (MIH) elicits beneficial cardiovascular and autonomic outcomes in males with obstructive sleep apnea (OSA) and concurrent ...

4. journals.physiology.org journals.physiology.org/doi/abs/10.1152/physiol.2025.40.S1.1536

Repeated Daily Exposure to Mild Intermittent Hypoxia ... Conclusion: Our results suggest that exposure to dMIH treatment combined with nightly CPAP use results in improved upper airway patency as ...

5. withpower.com withpower.com/trial/phase-2-sleep-apnea-syndromes-2023-7f728

Mild Intermittent Hypoxia for Obstructive Sleep Apnea Research suggests that mild intermittent hypoxia (IH) can lead to beneficial outcomes, such as increased stability of the upper airway, which may help reduce ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5085272/

Chronic intermittent hypoxia and obstructive sleep apnea A recent study showed that exposure to moderate IH (8% O2) with 20 hypoxic events/hour for 6 hours/day offers neuroprotection against brain lesion and cognitive ...

7. journals.physiology.org journals.physiology.org/doi/10.1152/physiol.2024.39.S1.1348

Repeated daily exposure to mild intermittent hypoxia leads ... Repeated daily exposure to mild intermittent hypoxia leads to a 8 week reduction in blood pressure and improvement in microvascular function in ...