OSA Treatment for Sleep Apnea

(ESSENTIAL Trial)

Recruiting at 3 trial locations

Overseen By Lisa Takemori

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: California Pacific Medical Center Research Institute

Must not be taking: Sedatives, Stimulants, Neuroleptics, others

Disqualifiers: Chronic insomnia, CNS disease, others

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

Compensation: Varies

Number of Visits: 15

Duration: 3 months

200 Participants Needed

Trial Summary

What is the purpose of this trial?

The Effects of Successful OSA TreatmENT on Memory and AD BIomarkers in Older AduLts (ESSENTIAL) study is a 5-year, multicenter randomized open-label trial that will screen 400 cognitively normal older adults recruited from well-established sleep clinics at 4 academic medical centers, with newly diagnosed moderate-severe OSA. An expected 200 OSA patients will be then randomized to one of two groups: i) a 3-month OSA treatment by any combination of PAP, OAT, and positional therapy that results in an "effective" AHI4%\< 10/hour and AHI3A\<20/hour (see below); ii) a waitlist control group to receive treatment at the conclusion of the 3-month intervention period. Both groups will continue follow-up for 24 months on stable therapy to determine if sustained improvements in sleep are associated with improvement in cognitive function and AD biomarkers.

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 sedatives, stimulants, or certain other drugs that could affect cognitive tests. Melatonin is allowed.

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

Mandibular advancement devices (MADs) are effective in treating obstructive sleep apnea (OSA) by improving the Apnea Hypopnea Index and symptoms in 92% of patients, especially for those with mild to moderate OSA or severe cases intolerant to CPAP. Positional therapy also helps by keeping the airway open in positional OSA, though its evidence base is still developing. ^{1 2 3 4 5}

Is the OSA treatment generally safe for humans?

Mandibular advancement devices (MADs) are generally considered safe for treating obstructive sleep apnea, although they may cause long-term changes in the position of teeth and jaw alignment. Patients often prefer MADs over CPAP, and they are recommended for those with mild to moderate sleep apnea or those who cannot tolerate CPAP. ^{3 4 6 7 8}

How does the OSA Treatment for Sleep Apnea differ from other treatments?

The OSA Treatment for Sleep Apnea is unique because it combines oral appliance therapy, positional therapy, and positive airway pressure, offering multiple approaches to keep the airway open during sleep. This combination allows for personalized treatment, especially for those who cannot tolerate CPAP (a machine that uses mild air pressure to keep the airways open) or have specific sleep positions that worsen their condition. ^{1 4 5 9 10}

Research Team

Andrew Varga, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Katie L Stone, PhD

Principal Investigator

California Pacific Medical Center Research Institute

Ricardo Osorio, MD

Principal Investigator

New York University

Eligibility Criteria

This trial is for adults aged 55-75 with moderate to severe obstructive sleep apnea (OSA), who are cognitively normal, have at least a high school education, and can speak English or Spanish. They shouldn't be on OSA treatment already or have other sleep disorders, significant brain vascular damage, serious health issues, drug abuse history, or be taking certain medications affecting cognition.

Inclusion Criteria

I am willing to receive treatment for sleep apnea.

I have moderate to severe sleep apnea with significant breathing pauses.

Cognitively normal (MoCA≥24, Clinical Dementia Rating [CDR]=0) with a minimum of 12 years of education

Exclusion Criteria

I do not have serious health issues like hormone disorders, blood diseases, substance abuse, mental health issues, brain conditions, or pregnancy.

I need extra oxygen due to a sleep or breathing issue.

I have no history of stroke, transient ischemic attacks, or significant brain lesions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

A 3-month OSA treatment by any combination of PAP, OAT, and positional therapy

3 months

Baseline, 3 months

Follow-up

Participants are monitored for sustained improvements in sleep and cognitive function

24 months

12 months (cognitive evaluation), 24 months (blood draw and cognitive evaluations)

Waitlist Control

Participants in the waitlist control group receive treatment after the 3-month intervention period

3 months

Treatment Details

Interventions

• Oral appliance therapy
• Positional therapy
• Positive airway pressure

Trial Overview The ESSENTIAL study tests if treating OSA in older adults improves memory and Alzheimer's disease biomarkers. Participants will either receive immediate OSA treatment using PAP, oral appliances or positional therapy for three months or be placed on a waitlist control group with later treatment. Both groups are followed up for two years.

Participant Groups

Group I: Waitlist control group Experimental Treatment 3 Interventions

A waitlist control group to receive treatment at the conclusion of the 3-month intervention period.

Group II: 3-month OSA treatment Active Control 3 Interventions

A 3-month OSA treatment by any combination of PAP, OAT, and positional therapy that results in an "effective" AHI3a\<15 (rapid multi-modal treatment RMMT).

Oral appliance therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Oral appliance therapy for:

• Obstructive sleep apnea (OSA)

Approved in European Union as Oral appliance therapy for:

• Obstructive sleep apnea (OSA)

Approved in Canada as Oral appliance therapy for:

• Obstructive sleep apnea (OSA)

Who Is Running the Clinical Trial?

California Pacific Medical Center Research Institute

Lead Sponsor

Trials

44

Recruited

10,600+

University of Arizona

Collaborator

Trials

545

Recruited

161,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Icahn School of Medicine at Mount Sinai

Collaborator

Trials

933

Recruited

579,000+

New York University

Collaborator

Trials

249

Recruited

229,000+

Findings from Research

Mandibular advancement devices (MADs) are an effective treatment for mild to moderate obstructive sleep apnea (OSA) and can also be used for severe cases when patients cannot tolerate positive airway pressure, as they help keep the airway open by mechanically moving the jaw forward.

Positional therapy, which encourages patients to avoid sleeping on their backs, shows promise for treating positional OSA, but the evidence supporting its effectiveness is still developing compared to MADs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-positive airway pressure modalities: mandibular advancement devices/positional therapy. Chan, AS., Lee, RW., Cistulli, PA.[2008]

Mandibular advancement devices (MADs) are an effective non-invasive treatment for obstructive sleep apnea (OSA), showing improvement in the Apnea Hypopnea Index and symptoms in 92% of patients across the studies reviewed.

The systematic review included 15 eligible studies, indicating a strong consensus on the efficacy of MADs, and suggests future advancements may involve integrating biosensors for better diagnosis and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral appliance therapy in obstructive sleep apnea and snoring - systematic review and new directions of development. Ilea, A., Timuș, D., Höpken, J., et al.[2021]

Mandibular advancement devices (MADs) significantly reduce the severity of obstructive sleep apnea (OSA) more effectively in patients with positional OSA compared to those with nonpositional OSA, based on a study of 72 patients.

The study found that the decrease in apnea severity, measured by the apnea-hypopnea index (AHI), was strongly associated with being in the positional group, indicating that MADs are particularly beneficial for this type of OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment outcomes of mandibular advancement devices in positional and nonpositional OSA patients. Chung, JW., Enciso, R., Levendowski, DJ., et al.[2018]

Continuous positive airway pressure (CPAP) therapy is more effective than mandibular advancement devices (MAD) in reducing the apnea hypopnea index (AHI) in patients with obstructive sleep apnea, based on a review of 14 randomized controlled trials involving 496 patients.

While CPAP significantly improved AHI and reduced the percentage of lighter sleep stages, it was associated with a decrease in social functioning scores compared to MAD, indicating a trade-off between efficacy and quality of life aspects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous positive airway pressure versus mandibular advancement device in the treatment of obstructive sleep apnea: a systematic review and meta-analysis. Li, P., Ning, XH., Lin, H., et al.[2021]

In a study of 126 patients with moderate to severe obstructive sleep apnea (OSA), CPAP therapy was more effective than mandibular advancement devices (MAD) in reducing apnea-hypopnea index (AHI), but patients reported better compliance with MAD.

Despite CPAP's superior efficacy in reducing AHI, both treatments showed similar improvements in neurobehavioral outcomes and quality of life, suggesting that higher compliance with MAD may balance its lower efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health outcomes of continuous positive airway pressure versus oral appliance treatment for obstructive sleep apnea: a randomized controlled trial. Phillips, CL., Grunstein, RR., Darendeliler, MA., et al.[2022]

In a 5-year follow-up study of 172 patients with obstructive sleep apnea (OSA) who were intolerant to CPAP, mandibular advancement devices (MADs) showed a treatment success rate of 52%, with varying effectiveness based on the severity of OSA: 25% for mild, 52% for moderate, and 63% for severe cases.

Despite a decline in treatment success rates over time, patient satisfaction remained high, with 96.5% wanting to continue MAD therapy and 93.3% using the device for at least 4 hours per night, indicating good adherence and no new safety concerns during long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mandibular advancement device use in obstructive sleep apnea: ORCADES study 5-year follow-up data. Vecchierini, MF., Attali, V., Collet, JM., et al.[2022]

A study of 117 patients using mandibular advancement devices (MADs) for an average of 4.6 years revealed moderate long-term dentoskeletal side effects, including decreases in overbite and overjet, and changes in incisor inclinations.

Certain factors, such as being a current smoker or having a pre-existing anterior open-bite, were linked to more significant changes in dental measurements, highlighting the need for careful patient selection and regular monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term dentoskeletal side effects of mandibular advancement therapy in patients with obstructive sleep apnea: data from the Pays de la Loire sleep cohort. Baldini, N., Gagnadoux, F., Trzepizur, W., et al.[2022]

Mandibular advancement devices (MADs) are effective in reducing the apnoea/hypopnoea index (AHI) and daytime sleepiness in patients with mild to moderate obstructive sleep apnoea (OSA), making them a recommended treatment option, especially for those who cannot tolerate CPAP.

Patients often prefer MADs over CPAP, and custom-made devices that are properly adjusted can lead to better outcomes, particularly for those with increased upper airway size due to mandibular advancement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-CPAP therapies in obstructive sleep apnoea: mandibular advancement device therapy. Marklund, M., Verbraecken, J., Randerath, W.[2022]

Continuous positive airway pressure (CPAP) is more effective than mandibular advancement devices (MADs) in reducing the apnea-hypopnea index (AHI) and improving lowest oxygen saturation in patients with obstructive sleep apnea, based on a meta-analysis of eight studies involving randomized controlled trials.

While both CPAP and MADs effectively reduce AHI and lowest oxygen saturation, there was no significant difference in the Epworth sleepiness scale (ESS) scores between the two treatments, indicating that both options can be viable, with CPAP remaining the gold standard.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous Positive Airway Pressure vs Mandibular Advancement Devices in the Treatment of Obstructive Sleep Apnea: An Updated Systematic Review and Meta-Analysis. Pattipati, M., Gudavalli, G., Zin, M., et al.[2022]

A trial using a titratable thermoplastic mandibular advancement device (MAD) showed a strong correlation with treatment outcomes in patients who later received a custom-made MAD, indicating that the thermoplastic device can effectively predict success in reducing obstructive sleep apnea severity.

Out of 111 patients, only 36 were analyzed, revealing that while the thermoplastic MAD had a high positive predictive value (86%) for treatment success, its low negative predictive value (46%) suggests it may not reliably identify patients who will not benefit from the custom-made MAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting treatment response to mandibular advancement therapy using a titratable thermoplastic device. Trzepizur, W., Adrian, B., Le Vaillant, M., et al.[2021]

References

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

Non-positive airway pressure modalities: mandibular advancement devices/positional therapy. [2008]

2. England pubmed.ncbi.nlm.nih.gov

Oral appliance therapy in obstructive sleep apnea and snoring - systematic review and new directions of development. [2021]

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

Treatment outcomes of mandibular advancement devices in positional and nonpositional OSA patients. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Continuous positive airway pressure versus mandibular advancement device in the treatment of obstructive sleep apnea: a systematic review and meta-analysis. [2021]

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

Health outcomes of continuous positive airway pressure versus oral appliance treatment for obstructive sleep apnea: a randomized controlled trial. [2022]

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

Mandibular advancement device use in obstructive sleep apnea: ORCADES study 5-year follow-up data. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Long-term dentoskeletal side effects of mandibular advancement therapy in patients with obstructive sleep apnea: data from the Pays de la Loire sleep cohort. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Non-CPAP therapies in obstructive sleep apnoea: mandibular advancement device therapy. [2022]

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

Continuous Positive Airway Pressure vs Mandibular Advancement Devices in the Treatment of Obstructive Sleep Apnea: An Updated Systematic Review and Meta-Analysis. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Predicting treatment response to mandibular advancement therapy using a titratable thermoplastic device. [2021]