CPAP + Medication + Oxygen for Obstructive Sleep Apnea

(ExPRESSION Trial)

Overseen By Pamela DeYoung

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Diego

Must not be taking: Opioids, Benzodiazepines, Theophylline, others

Disqualifiers: Pregnancy, Heart disease, Cancer, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the causes of Obstructive Sleep Apnea (OSA) and evaluate how different treatments might work for individuals. Participants will try therapies such as CPAP (a machine that helps keep airways open), Eszopiclone (a sleep aid), and oxygen to determine which reduces symptoms like sleepiness and high blood pressure. The study seeks to understand if these treatments can be more effective based on the underlying cause of OSA. Suitable candidates have been diagnosed with OSA or suspect they have it and are not currently using effective treatment. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you regularly use medications that affect breathing, like opioids or sedatives, or if you are already using the study drug, Eszopiclone.

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

A previous study showed that eszopiclone helps people with obstructive sleep apnea stay asleep longer by making it harder to wake up during sleep. However, it may cause drowsiness the next day, especially without a full night's sleep.

Supplemental oxygen has improved oxygen levels in people with obstructive sleep apnea, which might help with high blood pressure during the day. However, oxygen therapy can sometimes prolong breathing pauses (apneas).

Eszopiclone is already approved for treating insomnia, indicating general safety, but possible side effects like morning drowsiness should be noted. Supplemental oxygen is usually safe, but its effects on sleep apnea can vary.

This trial is in an early phase, so researchers are still learning about the safety and effectiveness of these treatments when used together. Understanding how these treatments work with obstructive sleep apnea might help create more personalized therapies in the future. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores the combination of CPAP therapy with Eszopiclone and oxygen to treat obstructive sleep apnea (OSA), potentially enhancing the standard approach. Traditional treatments usually involve just CPAP, which keeps airways open during sleep, but can be uncomfortable for some. By introducing Eszopiclone, a sleep aid, the trial aims to improve sleep quality and adherence to CPAP therapy. The use of supplemental oxygen may further enhance oxygen levels during sleep, potentially reducing sleep disruptions and improving overall outcomes. This multi-faceted approach could offer a more effective and comfortable solution for those struggling with OSA.

What evidence suggests that this trial's treatments could be effective for Obstructive Sleep Apnea?

This trial will compare different treatment approaches for Obstructive Sleep Apnea (OSA). Research has shown that using a Continuous Positive Airway Pressure (CPAP) machine can reduce the severity of OSA. Studies have found that CPAP improves quality of life, reduces daytime sleepiness, and lowers high blood pressure. It is also associated with a reduced risk of heart problems and can help people live longer.

Participants in this trial may receive Eszopiclone, a sleep aid that does not worsen sleep apnea. Instead, it improves sleep quality by promoting longer and more efficient sleep. It also enhances the comfort of CPAP therapy, which can improve adherence.

Another treatment option in this trial is Supplemental Oxygen therapy. This can decrease the frequency of breathing interruptions during sleep and increase blood oxygen levels. However, it does not lower blood pressure in people with OSA. ^{6 7 8 9 10}

Who Is on the Research Team?

Atul Malhotra, MD

Principal Investigator

Professor, Medicine

Christopher Schmickl

Principal Investigator

Postdoc Fellow, Medicine

Are You a Good Fit for This Trial?

This trial is for men and women aged 21-65 with a physician's diagnosis of OSA, or suspected to have it, who are not active smokers/vapers and do not have uncontrolled high blood pressure, chronic lung disease requiring oxygen, recent hospitalization, heavy alcohol use, certain heart conditions, active cancer or other specific health issues. BMI must be between 20 - 35 kg/m2.

Inclusion Criteria

I am between 21 and 65 years old.

Your body mass index (BMI) is between 20 and 35.

I have been diagnosed with obstructive sleep apnea.

Exclusion Criteria

I have not been treated for any sleep disorders like narcolepsy.

I am following my treatment plan for sleep apnea.

I have been regularly taking Eszopiclone.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Studies

Two initial baseline overnight studies to assess participants' sleep patterns and OSA manifestations

2 weeks

2 visits (in-person)

Experimental Studies

Two experimental overnight studies where subjects receive Eszopiclone or oxygen in random order

2 weeks

2 visits (in-person)

Treatment

Participants receive CPAP therapy, either immediately or after a delay, for 8 weeks

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Continuous Positive Airway Pressure (CPAP)
• Eszopiclone
• Supplemental Oxygen

Trial Overview The study aims to understand why people develop Obstructive Sleep Apnea (OSA) and how this relates to the effectiveness of treatments like CPAP machines, eszopiclone medication for sleep aid, and supplemental oxygen therapy in managing symptoms such as sleepiness and high blood pressure.

How Is the Trial Designed?

Group I: Usual PAP Start Experimental Treatment 2 Interventions

After two initial baseline overnight studies, and two experimental overnight studies during which subjects will receive Eszopiclone (2mg before bedtime) or oxygen (4L/min via nasal cannula for the duration of the time in bed) in random order, subjects will remain untreated until they are set up with their clinically prescribed CPAP (typically takes about 8 weeks).

Group II: Early PAP Start Experimental Treatment 3 Interventions

After two initial baseline overnight studies, and two experimental overnight studies during which subjects will receive Eszopiclone (2mg before bedtime) or oxygen (4L/min via nasal cannula for the duration of the time in bed) in random order, subjects will be set up with a loaner CPAP for 8 weeks to initiate therapy right away.

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)
• Sleep Apnea Syndromes
• Sleep Wake Disorders

Approved in United States as CPAP for:

• Obstructive Sleep Apnea (OSA)
• Sleep Apnea Syndromes
• Sleep Wake Disorders

Approved in Canada as CPAP for:

• Obstructive Sleep Apnea (OSA)
• Sleep Apnea Syndromes
• Sleep Wake Disorders

Approved in Japan as CPAP for:

• Obstructive Sleep Apnea (OSA)
• Sleep Apnea Syndromes
• Sleep Wake Disorders

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Published Research Related to This Trial

Nasal continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea (OSA), but it can cause side effects that may lead to discontinuation of therapy.

In this report, two patients developed irritant contact dermatitis (ICD) after using CPAP masks for several years, highlighting a potential skin-related side effect of long-term CPAP use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irritant contact dermatitis due to the use of a continuous positive airway pressure nasal mask: 2 case reports and review of the literature. Egesi, A., Davis, MD.[2013]

The nasal expiratory positive airway pressure (EPAP) device significantly reduced the apnea-hypopnea index (AHI) from 15.7 to 4.7 events per hour after 12 months of treatment, indicating effective long-term management of obstructive sleep apnea (OSA).

Patients reported a 74.4% reduction in snoring and a significant decrease in daytime sleepiness, as measured by the Epworth Sleepiness Scale, demonstrating both efficacy and improved quality of life with excellent adherence to the device (89.3% of nights used).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term use of a nasal expiratory positive airway pressure (EPAP) device as a treatment for obstructive sleep apnea (OSA). Kryger, MH., Berry, RB., Massie, CA.[2021]

In a study involving 63 patients with obstructive sleep apnea, the use of the topical nasal steroid fluticasone propionate did not reduce nasal symptoms caused by CPAP therapy after four weeks of treatment.

There was no significant difference in CPAP adherence between patients using fluticasone and those using a placebo, indicating that the steroid did not improve compliance with CPAP despite its common prescription for nasal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical nasal steroid treatment does not improve CPAP compliance in unselected patients with OSAS. Strobel, W., Schlageter, M., Andersson, M., et al.[2015]

In a study of 46 adults with obstructive sleep apnea, both Fixed CPAP and Auto-adjusting Pressure (APAP) significantly reduced the Apnoea Hypopnoea Index (AHI) to similar levels, indicating both are effective treatments.

Patient preference leaned towards APAP, especially among those with a higher BMI, suggesting that while both therapies are effective, individual comfort and pressure settings may influence treatment choice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing fixed and auto adjusting continuous positive airway pressure (CPAP) amongst symptomatic Obstructive Sleep Apnoea patients - A randomised controlled trial. Gan, WL., Ban, AYL., Mohamed Faisal, AH.[2021]

In a study of 227 patients with obstructive sleep apnea, adherence to positive airway pressure (PAP) treatment declined over time for all groups, but initial adherence levels influenced the effectiveness of subsequent interventions.

Motivational enhancement therapy (MET) was particularly beneficial for patients with moderate initial adherence, while education (ED) was more effective for those with high initial adherence, suggesting that tailored approaches based on early adherence can improve long-term treatment compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motivational enhancement to improve adherence to positive airway pressure in patients with obstructive sleep apnea: a randomized controlled trial. Aloia, MS., Arnedt, JT., Strand, M., et al.[2022]

EPAP nasal devices are a promising treatment for obstructive sleep apnea (OSA), showing a reduction in the apnea/hypopnea index (AHI) and daytime sleepiness, with patients generally preferring them over CPAP.

While CPAP is more effective for improving sleep apnea, EPAP can provide similar symptom relief for patients with mild to moderate OSA who cannot tolerate CPAP, although more well-designed clinical trials are needed to fully assess its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of EPAP nasal device therapy for obstructive sleep apnea syndrome. Wu, H., Yuan, X., Zhan, X., et al.[2021]

In a case study of a patient with obstructive sleep apnea syndrome (OSAS), the use of nasal continuous positive airway pressure (NCPAP) allowed for safe management during general anesthesia despite the use of conventional anesthetics and analgesics.

NCPAP not only prevented airway obstruction but also minimized pain during the perioperative period, suggesting it can effectively support anesthesia in OSAS patients without major complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative management of obstructive sleep apnea with nasal continuous positive airway pressure. Arisaka, H., Sakuraba, S., Kobayashi, R., et al.[2021]

In a study of 21 patients with central sleep apnea and related conditions, both noninvasive positive pressure ventilation (NPPV) and adaptive servoventilation (ASV) significantly reduced apnea/hypopnea index (AHI) and respiratory arousal index (RAI), indicating their effectiveness in improving breathing and sleep quality.

ASV was found to be more effective than NPPV in lowering AHI and RAI, suggesting that ASV may be the preferred treatment option for patients with centrally mediated breathing abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive servoventilation versus noninvasive positive pressure ventilation for central, mixed, and complex sleep apnea syndromes. Morgenthaler, TI., Gay, PC., Gordon, N., et al.[2022]

In a study involving 36 outpatients with obstructive sleep apnea syndrome (OSAS), automatic CPAP machines using estimated reference pressures were found to be as effective as those using fixed pressures in alleviating sleep and breathing disorders.

The results suggest that automatic CPAP can be effectively administered without the need for a titration sleep study, allowing for easier adjustments based on individual characteristics, although one patient did experience treatment failure due to an underestimated pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of automatic continuous positive airway pressure therapy that uses an estimated required pressure in the treatment of the obstructive sleep apnea syndrome. Sériès, F., Marc, I.[2019]

In a study of 497 patients undergoing CPAP titration, those using oronasal masks required higher CPAP pressures and experienced worse sleep outcomes, including lower sleep efficiency and higher residual apnea-hypopnea index, compared to those using nasal or pillow masks.

The findings suggest that oronasal masks are less effective for treating obstructive sleep apnea and should not be the first choice for patients, as they can lead to poorer overall sleep quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing CPAP masks during initial titration for Obstructive Sleep Apnea Syndrome: one-year experience. Zonato, AI., Rosa, CFA., Oliveira, L., et al.[2023]

In a study of 59 obstructive sleep apnea (OSA) patients who were non-adherent to CPAP, 80% tolerated a new expiratory positive airway pressure (EPAP) nasal device, leading to significant reductions in apnea-hypopnea index (AHI) from 43.3 to 27.0 events per hour (p<0.001).

The EPAP device showed a high adherence rate of 92% during sleep, and patients reported improved sleepiness scores, indicating that it may be an effective and convenient alternative treatment for OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A convenient expiratory positive airway pressure nasal device for the treatment of sleep apnea in patients non-adherent with continuous positive airway pressure. Walsh, JK., Griffin, KS., Forst, EH., et al.[2011]

In a study of 77 patients with obstructive sleep apnea syndrome (OSAS), those who accepted CPAP treatment had significantly lower nasal resistance and higher apnea/hypopnea indices, indicating that nasal airflow is crucial for CPAP acceptance.

Nasal resistance was identified as a significant predictor of whether patients would accept CPAP therapy, suggesting that addressing nasal obstruction may improve treatment adherence for OSAS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of nasal resistance on initial acceptance of continuous positive airway pressure in treatment for obstructive sleep apnea syndrome. Sugiura, T., Noda, A., Nakata, S., et al.[2009]

Citations

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IMPACT OF CONTINOUS POSITIVE AIRWAY PRESSURE ... We found that long-term improvement in quality of life occurs with the use of CPAP in persons with severe and possibly moderate sleep apnea.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6374080/

Treatment of Adult Obstructive Sleep Apnea With Positive ... Overall, the analyses support the conclusion that CPAP is effective in reducing OSA severity as measured by the AHI or RDI, across the spectrum of OSA severity.

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Positive airway pressure therapy adherence and outcomes ... In patients with OSA, PAP therapy has been shown to significantly reduce daytime sleepiness and hypertension; improve quality of life measures3, ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2590041224000151

Continuous positive airway pressure treatment for ... This is consistent with previous data showing that optimal CPAP adherence is associated with reduced risk of major adverse cardiovascular events [6] and road ...

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Positive Airway Pressure, Mortality, and CV Risk in Older ... In this cohort study of Medicare beneficiaries with OSA, PAP utilization was associated with lower all-cause mortality and MACE incidence.

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LUNESTA® (eszopiclone) tablets - accessdata.fda.gov The risk of next-day psychomotor impairment is increased if LUNESTA is taken with less than a full night of sleep remaining (7- to 8 hours); if higher than the ...

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Safety and Efficacy of Eszopiclone With Mild to Moderate ... This study will compare the use of eszopiclone to placebo for subjects with mild to moderate obstructive sleep Apnea syndrome (OSAS). Frequency and duration of ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3415379/

Eszopiclone increases the respiratory arousal threshold and ... Eszopiclone increases the arousal threshold and lowers the AHI in obstructive sleep apnoea patients that do not have marked overnight hypoxaemia.

9. go.drugbank.com go.drugbank.com/drugs/DB00402

Eszopiclone: Uses, Interactions, Mechanism of Action Eszopiclone is a sedative-hypnotic used in the treatment of insomnia, improving both the latency phase and the maintenance phase of sleep.

10. reference.medscape.com reference.medscape.com/drug/lunesta-eszopiclone-342927

Lunesta (eszopiclone) dosing, indications, interactions, ... Data in adults (aged 25-40 yr) taking eszopiclone 3 mg showed blood levels may remain high enough the following morning (7.5 hr after administration) to ...