Obstructive Sleep Apnea (OSA)CRESCENDONCT06983769
CPAP vs MAD for OSA in Patients With Cognitive Impairment. A Randomized Clinical Trial
A study testing MAD and CPAP in people with Obstructive Sleep Apnea (OSA) and Mild Cognitive Impairment, run by National University Hospital, Singapore at 1 site in Singapore.
Trial 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… Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Obstructive Sleep Apnea (OSA), Mild Cognitive Impairment
- What is being tested?
- MAD and CPAP
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 260 participants
- Where
- 1 siteSingapore
- Study dates
- 1 Jan 2026to 31 Dec 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Singapore1 site, 1 recruiting
- Recruiting
National University Hospital
Kent Ridge, Please Select, 267383
Chi-Hang Lee, MD, 91263120, mdclchr@nus.edu.sg
About this study
Official title: Cognition Recovery in Sleep Apnea Patients With Cardiovascular Risk by Evaluating Nasal CPAP Versus Dental Oral Appliance
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.
Read the detailed description
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
- Being tested
- MAD, CPAP
- Keywords
- Sleep, Cognition, Mandibular advancement device, CPAP, Clinical trial,
- Medical subject headings
- Sleep Apnea, Obstructive, Cognitive Dysfunction, Microcephaly, Primary Autosomal Recessive, 6
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MADDevice
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
CPAPDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: MAD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montreal Cognitive Assessment (MoCA)
A score for cognitive function
Measured: Baseline, 6 months (primary endpoint), and 12 months
Secondary outcomes (7)
Ambulatory Blood Pressure
Blood Pressure
Measured: Baseline, 6 months and 12 months
Epworth Sleepiness Scale
Measure of daytime sleepiness
Measured: Baseline, 6 months and 12 months
Sleep Apnea Quality of Life Index (SAQLI)
Sleep-related quality of life
Measured: Baseline, 6 months and 12 months
EQ-5D-5L
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.
Measured: Baseline, 6 months and 12 months
Residual AHI
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.
Measured: Baseline, 6 months and 12 months
Device adherence
Device adherence will be monitored based on the adherence sensors of the MAD and CPAP
Measured: 6 months and 12 months
Biomarkers
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]
Measured: Baseline, 6 months, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2025
- Study start1 Jan 2026
- Primary completion30 Jun 2030 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obstructive Sleep Apnea (OSA)Studies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 260 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- National University of Singapore, Ng Teng Fong General Hospital, Alexandra Hospital, National University Heart Centre, Singapore, University of Sydney
- Responsible party
- Principal investigator, Cardiac, National University Hospital, Singapore
- Investigators
- Chi-Hang Ronald Lee, MBBS, MD, Principal investigator, National University Heart Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06983769
- Sponsor's protocol ID
- ECOS. 2024-3614
- Acronym
- CRESCENDO
- Status last verified
- Jan 2026
- First submitted
- 22 Apr 2025
- Last updated
- 21 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cognition Recovery in Sleep Apnea Patients With Cardiovascular Risk by Evaluating Nasal CPAP Versus Dental Oral Appliance
- ClinicalTrials.gov ID
- NCT06983769
- Acronym / sponsor ID
- CRESCENDO / ECOS. 2024-3614
- Keywords
- Sleep, Cognition, Mandibular advancement device, CPAP, Clinical trial,
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 260 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Collaborators
- National University of Singapore, Ng Teng Fong General Hospital, Alexandra Hospital, National University Heart Centre, Singapore, University of Sydney
- Study start
- 1 Jan 2026 (actual)
- Primary completion
- 30 Jun 2030 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 21 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CPAP arm | Active comparator | Device: CPAPCPAP 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. |
| MAD | Experimental | Device: MADMAD 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. |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MADMandibular 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 |
| CPAPCPAP 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 arm |
Primary outcome
Montreal Cognitive Assessment (MoCA)
Time frame: Baseline, 6 months (primary endpoint), and 12 months
A score for cognitive function
7 secondary outcomes
Ambulatory Blood Pressure
Time frame: Baseline, 6 months and 12 months
Epworth Sleepiness Scale
Time frame: Baseline, 6 months and 12 months
Sleep Apnea Quality of Life Index (SAQLI)
Time frame: Baseline, 6 months and 12 months
EQ-5D-5L
Time frame: Baseline, 6 months and 12 months
Residual AHI
Time frame: Baseline, 6 months and 12 months
Device adherence
Time frame: 6 months and 12 months
Biomarkers
Time frame: Baseline, 6 months, 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Chi-Hang Ronald Lee, MBBS, MD principal investigator
National University Heart Centre, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MAD and CPAP in people with Obstructive Sleep Apnea (OSA) and Mild Cognitive Impairment, run by National University Hospital, Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chi-Hang Lee, MBBS, MD (+6567722493 ext. 2493, mdclchr@nus.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montreal Cognitive Assessment (MoCA) (time frame: Baseline, 6 months (primary endpoint), and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2026.