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

Trial Summary

What is the purpose of this trial?

Mild intermittent hypoxia (IH) initiates sustained increases in chest wall and upper airway muscle activity in humans. This sustained increase is a form of respiratory plasticity known as long-term facilitation (LTF). Repeated daily exposure to mild IH that leads to the initiation of LTF of upper airway muscle activity could lead to increased stability of the upper airway. In line with PI's laboratory's mandate to develop innovative therapies to treat sleep apnea, this increased stability could ultimately reduce the continuous positive airway pressure (CPAP) required to treat obstructive sleep apnea (OSA) and improve compliance with this gold standard treatment. Improved compliance could ultimately serve to mitigate those comorbidities linked to sleep apnea. Moreover, in addition to improving CPAP compliance numerous studies indicate that mild IH has many direct beneficial effects on cardiovascular, neurocognitive and metabolic function. Thus, mild IH could serve as a multipronged therapeutic approach to treat sleep apnea. In accordance with this postulation, our proposal will determine if repeated daily exposure to mild IH serves as an adjunct therapy coupled with CPAP to mitigate associated co-morbidities via its direct effects on a variety of cardiovascular, metabolic and neurocognitive measures and indirectly by improving CPAP compliance. Modifications in autonomic (i.e. sympathetic nervous system activity) and cardiovascular (i.e. blood pressure) function will be the primary outcome measures coupled to secondary measures of metabolic and neurocognitive outcomes.

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.

What data supports the effectiveness of this treatment for sleep apnea?

Research shows that CPAP therapy is effective in treating moderate to severe sleep apnea, improving symptoms, and reducing cardiovascular risks. However, its benefits for mild cases are less clear, though it may still help with daytime function. ^{1 2 3 4 5}

Is mild intermittent hypoxia safe for humans?

The research articles primarily discuss CPAP therapy, which is generally considered safe for treating sleep apnea, though it can be uncomfortable for some users. There is no specific safety data on mild intermittent hypoxia in these articles. ^{2 5 6 7 8}

How does CPAP therapy differ from other treatments for sleep apnea?

CPAP therapy is unique because it uses a machine to deliver a steady stream of air through a mask to keep the airways open during sleep, which is different from other treatments that might involve lifestyle changes or surgery. It is considered the gold standard for treating obstructive sleep apnea, but it can be uncomfortable for some patients, leading to compliance issues. ^{1 5 9 10 11}

Research Team

Jason H Mateika, Ph.D.

Principal Investigator

Wayne State University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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 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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Effect of CPAP therapy on daytime function in patients with mild sleep apnoea/hypopnoea syndrome. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Effect of CPAP therapy on cardiovascular events and mortality in patients with obstructive sleep apnea: a meta-analysis. [2022]

3. Hungary pubmed.ncbi.nlm.nih.gov

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

4. England 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Compliance with CPAP therapy in patients with the sleep apnoea/hypopnoea syndrome. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Comparison of three ways to determine and deliver pressure during nasal CPAP therapy for obstructive sleep apnoea. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Modafinil effects during acute continuous positive airway pressure withdrawal: a randomized crossover double-blind placebo-controlled trial. [2018]

8. England 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. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Exposure to intermittent hypoxia and sustained hypercapnia reduces therapeutic CPAP in participants with obstructive sleep apnea. [2019]

10. England 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. [2023]

11. Korea (South) pubmed.ncbi.nlm.nih.gov

Postoperative use of high flow nasal insufflation for obstructive sleep apnea. [2020]