A Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling

NCT04119999 | Completed DMC

• 1 other identifier: Senior CSA
• Study Type: interventional
• Target: 321
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this proposal is to evaluate whether mandibular advancement device (MAD) is non-inferior to continuous positive airway pressure (CPAP) in the treatment of obstructive sleep apnea (OSA) and blood pressure reduction. OSA and hypertension are highly prevalent disorders with profound impacts on health. Apart from improving quality of-life, an effective OSA treatment could improve cardiovascular risk partly through blood pressure reduction, particularly in patients with high cardiovascular risk in whom blood pressure control is often suboptimal. Although CPAP is useful, the high non-acceptance and non-adherence preclude its widespread use. East Asians have a restrictive craniofacial phenotype that predisposes them to OSA and the associated cardiovascular stress. CPAP, while considered the first-line therapy for OSA, has failed to improve cardiovascular outcomes in randomized trials till date because it is poorly tolerated. MADs are oral appliances that correct the restrictive craniofacial phenotype present in East Asians by protruding the lower jaw to reduce upper airway collapsibility. MADs are better tolerated than CPAP, and this may be an important determinant of the overall effectiveness in treating OSA, and thus ameliorating the downstream adverse health outcomes. We hypothesize that MADs are non-inferior to CPAP in treating OSA and reducing cardiovascular risk by blood pressure reduction in East Asians. We will recruit East Asian subjects with hypertension and high cardiovascular risk for polysomnography. Patients diagnosed with OSA (n=220) will be randomized to MAD or CPAP groups in a 1:1 ratio for a treatment duration of 6 months. The primary endpoint is the 24-hour mean blood pressure as determined by ambulatory monitoring. The secondary endpoints include sleep-time systolic BP, target blood pressure, cardiovascular biomarkers, and myocardial remodeling. Association between OSA and silent paroxysmal atrial fibrillation will also be determined. If MADs are shown to be effective, the next step is to evaluate our novel device- drug-eluting MAD that the team is developing.

Conditions

Hypertension,Essential; Obstructive Sleep Apnea

Keywords

sleep; remodeling; blood pressure; trial

Outcome Measures

Primary Outcomes (1)

• 24-hour mean BP (24MBP)

  Difference in 24-hour mean BP (24MBP) between the patients in the MAD and CPAP groups as determined by 24-hour ambulatory BP monitoring.

  6 months

Secondary Outcomes (17)

• 24-hour systolic BP (24SBP)

  6 months and 12 months

• 24-hour pulse pressure (24PP)

  6 months and 12 months

• Nocturnal dipping

  6 months and 12 months

• Ectopic beat

  12 months

• Myocardial remodeling

  12 months

Other Outcomes (1)

• Subgroup analysis

  6 months and 12 months

Study Arms (2)

CPAP

ACTIVE COMPARATOR

Continuous Positive Airway Pressure

Device: Continuous Positive Airway Pressure

MAD

EXPERIMENTAL

Mandibular Advancement Device

Device: Mandibular Advancement Device

Interventions

Mandibular Advancement Device DEVICE

Mandibular advancement device (MAD) has been a novel method in the management of snoring and OSA. For mild to moderate sleep apnea, MADs have been a boon. A guideline published by American Academy of Sleep Medicine stated that MAD was indicated as first-line therapy for mild OSA and a second-line therapy for moderate to severe OSA

MAD

Continuous Positive Airway Pressure DEVICE

Continuous positive airway pressure (CPAP) is a form of positive airway pressure ventilator, which applies mild air pressure on a continuous basis to keep the airways continuously open in people with OSA

CPAP

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of at least 40 years
• Chinese (based on the Identity Card or other Identity Document if the subject is a non-Singapore citizen or permanent resident)
• Physician diagnosed essential hypertension, on at least 1 medication for BP control
• High cardiovascular risk, as defined by one or more of the following: (a) diabetes mellitus, (b) stroke, (c) significant coronary artery disease (at least one stenosis of \>50% diameter in at least one major epicardial artery), (d) chronic kidney disease, excluding polycystic kidney disease, with an estimated glomerular filtration rate of \<60 ml/min/1.73m2, or (e) age of 75 years or older.

You may not qualify if:

• Known OSA on treatment
• Cheyne-Stokes breathing or predominantly central sleep apnea (\>50%)
• Known secondary hypertension: from renal (renal artery stenosis, chronic renal failure); endocrine (aldosterone excess, pheochromocytoma, cushing's syndrome, hyperthyroidism) or cardiac causes (aortic coarctation)
• Contraindications to CMR: implantable devices, cerebral aneurysm clips, cochlear implants, renal impairment (GRF \<30ml/min/1.73m2), claustrophobia and pregnant women
• Contraindications to MAD: \<6 to 10 teeth in each arch, inability to advance the mandible and open the jaw widely, pre-existing temporomandibular joint problems, severe bruxism
• Limited life expectancy (\< 1 year)
• Hypertensive crisis, acute coronary syndromes or acute heart failure in the past 30 days
• Known AF (not suitable for CMR and affects remodelling analysis)

Sponsors & Collaborators

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

Study Sites (1)

NUHS Cardiosleep research laboratory

Singapore, Singapore

Location

Related Publications (4)

• Colpani JT, Ou YH, Kosasih AM, Lee FKF, Chan SP, Tan HH, Wong RCW, Chin CW, Cistulli PA, Lee CH. Mandibular Advancement Device versus CPAP in Severe Obstructive Sleep Apnea. J Dent Res. 2026 Jan;105(1):112-119. doi: 10.1177/00220345251361796. Epub 2025 Sep 1.

  PMID: 40888163 DERIVED

• Colpani JT, Ou YH, Thakumar AV, Cheong CS, Loke W, Sia CH, Teo YH, Chan SP, Chin CW, Kojodjojo P, Chan MY, Cistulli PA, Luo N, Lee CH. Patient-reported quality of life outcomes with mandibular advancement versus continuous positive airway pressure: insights from the CRESCENT trial. Sleep. 2025 Nov 10;48(11):zsaf022. doi: 10.1093/sleep/zsaf022.

  PMID: 39887015 DERIVED

• Ou YH, Colpani JT, Cheong CS, Loke W, Thant AT, Shih EC, Lee F, Chan SP, Sia CH, Koo CY, Wong S, Chua A, Khoo CM, Kong W, Chin CW, Kojodjojo P, Wong PE, Chan MY, Richards AM, Cistulli PA, Lee CH. Mandibular Advancement vs CPAP for Blood Pressure Reduction in Patients With Obstructive Sleep Apnea. J Am Coll Cardiol. 2024 May 7;83(18):1760-1772. doi: 10.1016/j.jacc.2024.03.359. Epub 2024 Apr 6.

  PMID: 38588926 DERIVED

• Ou YH, Colpani JT, Chan SP, Loke W, Cheong CS, Kong W, Chin CW, Kojodjojo P, Wong P, Cistulli P, Lee CH. Mandibular advancement device versus CPAP in lowering 24-hour blood pressure in patients with obstructive sleep apnoea and hypertension: the CRESCENT trial protocol. BMJ Open. 2023 May 31;13(5):e072853. doi: 10.1136/bmjopen-2023-072853.

  PMID: 37258080 DERIVED

MeSH Terms

Conditions

Essential Hypertension; Sleep Apnea, Obstructive

Interventions

Occlusal Splints; Continuous Positive Airway Pressure

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases; Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Orthotic Devices; Orthopedic Equipment; Surgical Equipment; Equipment and Supplies; Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy

Study Officials

• Chi-Hang Lee, MD

  National University of Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 7, 2019
• First Posted: October 9, 2019
• Study Start: October 16, 2019
• Primary Completion: August 31, 2023
• Study Completion: February 15, 2024
• Last Updated: February 20, 2024

Record last verified: 2024-02

Locations

SG (1)