Mild Intermittent Hypoxia for Obstructive Sleep Apnea

Overseen By Shipra Puri

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: VA Office of Research and Development

Must not be taking: Sleep supplements, others

Disqualifiers: High blood pressure, pulmonary hypertension, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for people with obstructive sleep apnea (OSA), a condition that disrupts breathing during sleep and can lead to cardiovascular issues and exercise fatigue. The treatment involves mild intermittent hypoxia (MIH), which means controlled exposure to lower oxygen levels. Researchers aim to determine if this can improve cardiovascular health and reduce exercise-related tiredness. Suitable participants include those with newly diagnosed sleep apnea, high blood pressure, and pre-diabetes, who have not yet tried CPAP therapy. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's effects and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in OSA treatment.

Will I have to stop taking my current medications?

Yes, participants must stop taking their current medications, except for a single prescribed medication for hypertension.

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

Research has shown that mild intermittent hypoxia (MIH) can be safe for people. In studies with older adults, 15 sessions of MIH reduced symptoms of stable angina, which is chest pain caused by reduced blood flow to the heart, without major safety issues. Other research has found that MIH can improve exercise ability and is generally well-tolerated. Additionally, daily exposure to mild MIH has been reported to lower blood pressure in people with obstructive sleep apnea (OSA) and high blood pressure.

Overall, these studies suggest that MIH is generally safe for humans, with few reports of side effects. This is encouraging, especially for those seeking new treatments for conditions like OSA. However, discussing potential risks with a healthcare provider before joining any clinical trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about mild intermittent hypoxia (MIH) for obstructive sleep apnea because it offers a novel approach by temporarily lowering oxygen levels to stimulate physiological adaptations. Unlike standard treatments like CPAP machines, which mechanically assist breathing during sleep, MIH aims to naturally enhance the body's response to low oxygen, potentially improving breathing patterns over time. This method could provide a less intrusive and more sustainable option for managing sleep apnea, addressing the root causes rather than just the symptoms.

What evidence suggests that mild intermittent hypoxia could be an effective treatment for obstructive sleep apnea?

Research has shown that mild intermittent hypoxia (MIH), which participants in this trial may receive, might benefit people with obstructive sleep apnea (OSA). Studies have found that MIH can lower blood pressure in individuals with OSA who also have high blood pressure. Other research indicates that MIH can enhance exercise ability and reduce fatigue during exercise, benefiting OSA patients. Additionally, MIH has been linked to improved cholesterol levels, which can enhance heart and blood vessel health. These findings suggest that MIH could be a promising new approach to improving health for those with OSA. ^{1 2 4 6 7}

Who Is on the Research Team?

Jason H Mateika, PhD MS BS

Principal Investigator

John D. Dingell VA Medical Center, Detroit, MI

Are You a Good Fit for This Trial?

This trial is for adults aged 30-60 with a BMI under 40, newly diagnosed obstructive sleep apnea (OSA), and hypertension. They must have normal lung function, EKG readings, controlled alcohol intake, and not be on CPAP treatment or multiple medications. Pre-diabetic individuals with specific cholesterol levels can join too.

Inclusion Criteria

My lung function is normal, my heart's electrical activity is normal, and I drink less than 2 oz of alcohol per night.

My lungs work normally, my heart's electrical activity is normal, and I drink less than 2 oz of alcohol nightly.

I have never used a CPAP machine before.

Exclusion Criteria

I have a known disease such as pulmonary hypertension.

I am only on one medication for high blood pressure that's hard to control.

Pregnant females

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mild intermittent hypoxia (MIH) or sham MIH treatment to assess its effects on sleep apnea and associated comorbidities

8 weeks

Daily visits (in-person) for MIH administration

Follow-up

Participants are monitored for changes in blood pressure, microvascular function, and other health outcomes after treatment

8 weeks

Regular follow-up visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Mild Intermittent Hypoxia
• Sham MIH

Trial Overview The study tests whether mild intermittent hypoxia (MIH) can improve heart health and reduce fatigue during exercise in OSA patients by increasing airway stability and enhancing sleep quality. It compares MIH to a sham procedure to see if it's an effective standalone or adjunct therapy.

How Is the Trial Designed?

Group I: Mild Intermittent Hypoxia (MIH) Experimental Treatment 1 Intervention

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.

Group II: Sham Mild Intermittent Hypoxia (Sham MIH) Placebo Group 1 Intervention

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

Mild Intermittent Hypoxia is already approved in United States, European Union for the following indications:

Approved in United States as Mild Intermittent Hypoxia for:

• Obstructive Sleep Apnea (OSA)
• Cardiovascular dysfunction
• Exercise performance fatigue

Approved in European Union as Intermittent Hypoxia-Hyperoxia Treatment for:

• Obstructive Sleep Apnea (OSA)
• Cardiovascular conditions
• Respiratory conditions

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

John D. Dingell VA Medical Center

Collaborator

Trials

10

Recruited

1,100+

Published Research Related to This Trial

Intermittent hypoxia (IH) negatively impacts the human nasal mucosa by decreasing ciliary beat frequency (CBF) and increasing inflammatory cytokines, which can lead to airway inflammation.

In a study comparing normoxic conditions to IH over 72 hours, the IH group exhibited significant changes in CBF and cytokine levels, but there was no difference in cell survival rates, suggesting that while IH affects mucosal function, it does not directly cause cell death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of intermittent hypoxia on human nasal mucosa. In, SM., Park, DY., Lee, KI., et al.[2021]

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]

Obstructive sleep apnea (OSA) involves frequent episodes of upper airway obstruction and hypoxia during sleep, leading to significant health issues and making it a major socio-sanitary concern, especially in adults over 35.

Carotid body chemoreceptors play a crucial role in the pathophysiology of OSA, suggesting that targeted research on these receptors could lead to better understanding and treatment strategies for the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Some reflections on intermittent hypoxia. Does it constitute the translational niche for carotid body chemoreceptor researchers? Gonzalez, C., Yubero, S., Gomez-Niño, MA., et al.[2021]

Both intermittent hypoxia/normoxia training (IHT) and intermittent hypoxia/hyperoxia training (IHHT) significantly reduced fasting glucose and cholesterol levels in prediabetic patients, with effects lasting up to one month after training ended.

IHHT may offer advantages over IHT by potentially reducing session duration due to shorter reoxygenation periods, making it a more efficient training method for improving metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Hypoxia/Hyperoxia Versus Intermittent Hypoxia/Normoxia: Comparative Study in Prediabetes. Serebrovska, TV., Grib, ON., Portnichenko, VI., et al.[2020]

Intermittent hypoxia (IH) may have beneficial effects, particularly in promoting respiratory plasticity that could help mitigate obstructive sleep apnea (OSA) when used alongside continuous positive airway pressure (CPAP) therapy.

Mild forms of IH could enhance the stability of the upper airway, potentially reducing the amount of CPAP needed, which may improve patient compliance and overall treatment outcomes for OSA and related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent hypoxia initiated plasticity in humans: A multipronged therapeutic approach to treat sleep apnea and overlapping co-morbidities. Mateika, JH., Komnenov, D.[2019]

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]

Intermittent hypoxia (IH) from obstructive sleep apnea (OSA) leads to significant systemic and vascular inflammation in mice, which contributes to cardiovascular complications, highlighting the need for better understanding of OSA's pathophysiology.

Blocking the RANTES/CCL5 signaling pathway during IH exposure prevented vascular inflammation and structural changes, suggesting that targeting this inflammatory response could be a potential treatment strategy for mitigating the cardiovascular risks associated with OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The inflammatory preatherosclerotic remodeling induced by intermittent hypoxia is attenuated by RANTES/CCL5 inhibition. Arnaud, C., Beguin, PC., Lantuejoul, S., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9168371/

Effects of Intermittent Hypoxia in Training Regimes and in ... The study showed the same positive effect of IHNT and IHHT: decreased total blood cholesterol and LDL; and an equally smaller drop in SpO2 ...

2. medsci.org medsci.org/v20p1551.htm

Intermittent Hypoxia Conditioning: A Potential Multi-Organ ... This review presents a comprehensive analysis of existing studies on intermittent hypoxia and its potential advantages in various organs.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03736382

Mild Intermittent Hypoxia and Its Multipronged Effect on ... Daily Exposure to Mild Intermittent Hypoxia Reduces Blood Pressure in Male Patients with Obstructive Sleep Apnea and Hypertension. Am J Respir Crit Care Med ...

4. liebertpub.com liebertpub.com/doi/10.1089/ham.2019.0053

Intermittent Hypoxia/Hyperoxia Versus ... However, hypoxic training significantly and equally reduced the level of LDLC in IHHT and IHT groups (by 17%). A low level of LDLC remained for ...

5. sportsmedicine-open.springeropen.com sportsmedicine-open.springeropen.com/articles/10.1186/s40798-022-00450-x

Effects of Intermittent Hypoxia–Hyperoxia on Performance ... In this context, studies have shown that intermittent hypoxic exposure improved aerobic capacity and exercise tolerance in elderly males with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9156652/

Effects of Intermittent Hypoxia–Hyperoxia on Performance In this context, studies have shown that intermittent hypoxic exposure improved aerobic capacity and exercise tolerance in elderly males with ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1569904824001514

Safety and effectiveness of acute intermittent hypoxia ... AIH is generally safe and effective for inducing neural plastic responses. · AIH does not impact cognition or cerebral perfusion rates. · AIH acutely results in a ...