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NCT Number: NCT06983769

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

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.

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Key information

Conditions

Obstructive Sleep Apnea (OSA) Apnea Cognition Disorders Cognitive Dysfunction Dyssomnias Mental Disorders Microcephaly, Primary Autosomal Recessive, 6 Mild Cognitive Impairment Nervous System Diseases Neurocognitive Disorders Respiration Disorders Respiratory Tract Diseases Sleep Apnea Syndromes Sleep Apnea, Obstructive Sleep Disorders, Intrinsic Sleep Wake Disorders

Age range

45 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

National University Hospital

Kent Ridge, Please Select, 267383, Singapore

Location status: Recruiting

Location contact

Chi-Hang Lee, MD

CONTACT

[email protected]

91263120

About this study

Aim #1: The primary objective is to compare the effectiveness of MAD and CPAP in improving cognitive function in participants with OSA and cardiovascular risk. The key endpoints of the trial will include cognitive function using the Montreal Cognitive Assessment (MoCA). Participants diagnosed with moderate-to-severe OSA, mild cognitive impairment, and cardiovascular risk will be randomly assigned to either the MAD or CPAP group (1:1). Baseline assessments, along with six- and twelve-month follow-ups, will include the administration of the MoCA. The analysis of covariance (ANCOVA) will be used to compare the between-group differences in the changes observed in various measures of cognitive function. We hypothesize that MAD is non-inferior to CPAP in improving cognitive function.

Aim #2: The second objective is to examine whether brain structural and functional integrity at baseline can predict cognitive recovery after OSA treatment. Besides traditional brain macrostructural measures (grey matter volume, cortical thickness, and white matter hyperintensity), we hypothesize that brain microstructural and functional measures at baseline capturing individual differences in cerebral blood flow (via perfusion), cerebrovascular damage (via diffusion-derived freewater in both grey matter and white matter), functional network in higher-order cognitive networks (via task-free fMRI), and blood-brain barrier integrity (diffusion-prepared perfusion) will predict post-treatment cognition in OSA patients (see Preliminary work).

Aim #3: To understand the relative contribution of the complex disease pathophysiology of OSA and its treatment in cognitive function. We aim to understand the relative contribution of the complex disease pathophysiology of OSA and its treatment in cognitive function. We will explore the relationship between improvement in MoCA score from baseline to 12 months follow-up and the following parameters (1) OSA pathophysiology: Epworth Sleepiness Scale, apnea-hypopnea index, oxygen desaturation index, time with SpO2<90% (T90), arousal index. (2) OSA treatment with CPAP/MAD: CPAP/MAD device adherence

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

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

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.

Primary outcomes

  1. Montreal Cognitive Assessment (MoCA)

    Time frame: Baseline, 6 months (primary endpoint), and 12 months

    A score for cognitive function

Secondary outcomes

  1. Ambulatory Blood Pressure

    Time frame: Baseline, 6 months and 12 months

    Blood Pressure

  2. Epworth Sleepiness Scale

    Time frame: Baseline, 6 months and 12 months

    Measure of daytime sleepiness

  3. Sleep Apnea Quality of Life Index (SAQLI)

    Time frame: Baseline, 6 months and 12 months

    Sleep-related quality of life

  4. EQ-5D-5L

    Time frame: Baseline, 6 months and 12 months

    Generic health-related quality-of-life measure across five domains (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), enhanced with four bolt-on items relevant to sleep and cardiovascular health, and a visual analogue scale (VAS) for self-rated health.

  5. Residual AHI

    Time frame: Baseline, 6 months and 12 months

    Residual AHI is a measure of treatment effectiveness. Trial participants will undergo overnight sleep studies at baseline (pre-treatment), 6-month, and 12-month follow-up.

  6. Device adherence

    Time frame: 6 months and 12 months

    Device adherence will be monitored based on the adherence sensors of the MAD and CPAP

  7. Biomarkers

    Time frame: Baseline, 6 months, 12 months

    NT-pro-BNP, high-sensitivity C-reactive protein, and high-sensitivity troponin, angiopoietin-2, Tie-2, Eselectin, vascular endothelial growth factor [VEGF-A]), and Soluble receptor of advanced glycation endproducts [sRAGE]

Study contacts

Contact information is provided by the study sponsor or research team.

Chi-Hang Lee, MBBS, MD

CONTACT

[email protected]

+6567722493 ext. 2493

Sponsors and collaborators

Lead sponsor

National University Hospital, Singapore

Other

Collaborators

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

Registry information

Official study title

Cognition Recovery in Sleep Apnea Patients With Cardiovascular Risk by Evaluating Nasal CPAP Versus Dental Oral Appliance

Acronym: CRESCENDO

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
May 21, 2025
Registry last updated
Jan 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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