CPAP vs MAD for OSA in Patients With Cognitive Impairment. A Randomized Clinical Trial

NCT06983769 | Recruiting DMC

• 1 other identifier: ECOS. 2024-3614
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 1

Brief Summary

Obstructive sleep apnea (OSA) is a prevalent condition that significantly impacts the sleep health and overall well-being of millions of adults worldwide. It is characterized by breathing difficulties during sleep caused by an obstructed upper airway, leading to fragmented sleep, oxygen deprivation, and increased sympathetic activity. OSA and its associated health problems contribute to an annual economic burden exceeding $150 billion in the United States. Studies have shown that individuals with OSA are 26% more likely to develop cognitive impairment compared to those without the condition. However, despite the effectiveness of continuous positive airway pressure (CPAP) therapy, many patients struggle with acceptance and adherence to this treatment. As an alternative, mandibular advancement devices (MADs) have gained acceptance among OSA patients by improving upper airway anatomy through repositioning of the jaw and tongue, thus reducing collapsibility. This non-invasive approach shows promise, particularly in addressing the unique craniofacial features commonly found in East Asian OSA patients. To further investigate the efficacy of MAD versus CPAP therapy, a multi-center, randomized clinical trial is proposed. The trial aims to evaluate cognitive function using established assessment tools and explore the relationship between different Asian ethnicities and changes in cognitive function, ambulatory blood pressure, and cerebral oxygen saturation. Additionally, brain MRI will be utilized to examine whether baseline brain structure and function can predict treatment response in OSA patients. Participants diagnosed with moderate-to-severe OSA will be randomly assigned to either the MAD or CPAP group in a 1:1 ratio. Baseline assessments, along with six-month and one-year follow-ups, will be conducted to assess the impact of the interventions. This trial seeks to provide valuable insights into the effectiveness of MAD versus CPAP therapy in Asian populations, specifically focusing on their effects on cognitive function and other relevant outcomes in individuals with OSA.

Conditions

Obstructive Sleep Apnea (OSA); Mild Cognitive Impairment

Keywords

Sleep, Cognition, Mandibular advancement device, CPAP, Clinical trial,

Outcome Measures

Primary Outcomes (1)

• Montreal Cognitive Assessment (MoCA)

  A score for cognitive function

  Baseline, 6 months (primary endpoint), and 12 months

Secondary Outcomes (7)

• Ambulatory Blood Pressure

  Baseline, 6 months and 12 months

• Epworth Sleepiness Scale

  Baseline, 6 months and 12 months

• Sleep Apnea Quality of Life Index (SAQLI)

  Baseline, 6 months and 12 months

• EQ-5D-5L

  Baseline, 6 months and 12 months

• Residual AHI

  Baseline, 6 months and 12 months

Study Arms (2)

CPAP arm

ACTIVE COMPARATOR

CPAP stands for Continuous Positive Airway Pressure. It is the standard treatment for obstructive sleep apnea (OSA). A CPAP machine delivers a constant stream of air through a mask worn over the nose or nose and mouth during sleep. This air pressure keeps the airway open, preventing pauses in breathing caused by airway collapse. CPAP is highly effective, especially for moderate to severe OSA, but some patients may find it uncomfortable or difficult to tolerate.

Device: CPAP

MAD

EXPERIMENTAL

MAD stands for Mandibular Advancement Device. It is a custom-fitted oral appliance used primarily to treat obstructive sleep apnea (OSA) and snoring. The device works by gently advancing the lower jaw (mandible) forward, which helps keep the airway open during sleep by preventing the tongue and soft tissues from collapsing and blocking the airway. MADs are a non-invasive alternative to CPAP therapy and are especially suitable for patients with mild to moderate OSA or those who are intolerant to CPAP.

Device: MAD

Interventions

MAD DEVICE

Mandibular Advancement Device. It is a custom-fitted oral appliance used primarily to treat obstructive sleep apnea (OSA) and snoring. The device works by gently advancing the lower jaw (mandible) forward, which helps keep the airway open during sleep by preventing the tongue and soft tissues from collapsing and blocking the airway. MADs are a non-invasive alternative to CPAP therapy and are especially suitable for patients with mild to moderate OSA or those who are intolerant to CPAP

MAD

CPAP DEVICE

CPAP stands for Continuous Positive Airway Pressure. It is the standard treatment for obstructive sleep apnea (OSA). A CPAP machine delivers a constant stream of air through a mask worn over the nose or nose and mouth during sleep. This air pressure keeps the airway open, preventing pauses in breathing caused by airway collapse. CPAP is highly effective, especially for moderate to severe OSA, but some patients may find it uncomfortable or difficult to tolerate.

CPAP arm

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of at least 45 Chinese, Malay, Indian Referred to the sleep clinics of the CRESCENDO participating centers for suspected OSA, underwent a clinically indicated level 1 polysomnography, and diagnosed to have moderate-to-severe OSA (AHI ≥ 15 events/hour) Mild cognitive impairment: MoCA score \<27 (for those with \>10 years of education) and \<26 (for those with ≤10 years of education) Agree to follow the study protocol

You may not qualify if:

• Known OSA and already on regular treatment Severe cognitive impairment (MoCA \<10) Severe hypoxemia on polysomnography ODI \>60 or min SpO2 \<60% Known schizophrenia, bipolar disorder, severe depression, drug abuse or alcohol abuse Contraindications to MAD: less than six teeth in each arch; inability to advance the mandible and open the jaw widely. Pre-existing temporomandibular joint problems, severe bruxism, and advanced periodontal disease Limited life expectancy (\< one year) Cardiac or cerebrovascular events leading to hospitalization in the past three months Complex cardiovascular diseases: cyanotic congenital heart disease, moderate to severe pulmonary hypertension On regular medications that could affect the neurocognitive function and/or alertness

Sponsors & Collaborators

• University of Sydney: collaborator
• Ng Teng Fong General Hospital: collaborator
• Alexandra Hospital: collaborator
• National University Heart Centre, Singapore: collaborator
• National University Hospital, Singapore: lead
• National University of Singapore: collaborator

Study Sites (1)

National University Hospital

Kent Ridge, Please Select, 267383, Singapore

RECRUITING

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Cognitive Dysfunction; Microcephaly, Primary Autosomal Recessive, 6

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Chi-Hang Ronald Lee, MBBS, MD

  National University Heart Centre, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chi-Hang Lee, MBBS, MD

CONTACT

+6567722493; mdclchr@nus.edu.sg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Investigators responsible for conducting the MoCA, quality of life questionnaires, and reading the MRI brain will be masked
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 22, 2025
• First Posted: May 21, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)