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NCT Number: NCT04119999

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

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.

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Key information

Conditions

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

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

NUHS Cardiosleep research laboratory

Singapore

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • 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.

Exclusion criteria

  • 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)

Treatment and study plan

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

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

Primary outcomes

  1. 24-hour mean BP (24MBP)

    Time frame: 6 months

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

Secondary outcomes

  1. 24-hour systolic BP (24SBP)

    Time frame: 6 months and 12 months

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

  2. 24-hour pulse pressure (24PP)

    Time frame: 6 months and 12 months

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

  3. Nocturnal dipping

    Time frame: 6 months and 12 months

    Difference in prevalence of nocturnal dipping between the patients in the MAD and CPAP groups as determined by 24-hour ambulatory BP monitoring.

  4. Ectopic beat

    Time frame: 12 months

    Difference in prevalence of ectopic beats between the patients in the MAD and CPAP groups as determined by continuous ECG monitoring

  5. Myocardial remodeling

    Time frame: 12 months

    Difference in LV and LA dimensions between the patients in the MAD and CPAP groups as determined by cardiac MRI

  6. Epworth Sleepiness Scale (ESS) score

    Time frame: 6 months and 12 months

    Difference in change in ESS score between the MAD and CPAP groups

  7. Sleep Apnea Quality of Life Index (SAQLI)

    Time frame: 6 months and 12 months

    Difference in change in SAQLI score between the MAD and CPAP groups

  8. Functional Outcome of Sleep Questionnaire (FOSQ)

    Time frame: 6 months and 12 months

    Difference in change in SAQLI score between the MAD and CPAP groups

  9. 36-Item Short Form Health Survey (SF-36)

    Time frame: 6 months and 12 months

    Difference in change in SF-36 score between the MAD and CPAP groups

  10. EuroQol 5Q (EQ5D)

    Time frame: 6 months and 12 months

    Difference in change in EQ5D score between the MAD and CPAP groups

  11. Daytime systolic BP

    Time frame: 6 months and 12 months

    Difference in change in daytime systolic BP between the patients in the MAD and CPAP

  12. Nighttime systolic BP

    Time frame: 6 months and 12 months

    Difference in change in nighttime systolic BP between the patients in the MAD and CPAP

  13. Percentage of patient with 24-hour systolic BP<130 mmHg

    Time frame: 6 months and 12 months

    Difference in percentage of patients with 24-hour systolic BP<130 mmHg in the MAD and CPAP groups

  14. Percentage of patient with 24-hour systolic BP<120 mmHg

    Time frame: 6 months and 12 months

    Difference in percentage of patients with 24-hour systolic BP<120 mmHg in the MAD and CPAP groups

  15. NT-proBNP

    Time frame: 6 months and 12 months

    Change in the plasma level of NT-proBNP from baseline to 6-month follow-up

  16. High sensitivity troponin

    Time frame: 6 months and 12 months

    Change in the plasma level of high sensitivity troponin from baseline to 6-month follow-up

  17. High sensitive C-reactive protein

    Time frame: 6 months and 12 months

    Change in the plasma level of high sensitive C-reactive protein from baseline to 6-month follow-up

Other outcomes

  1. Subgroup analysis

    Time frame: 6 months and 12 months

    Prespecified subgroups include - Age, Gender, BMI, wrist circumference, AHI, ODI, ESS, DM, IHD, number of HT medicine, Device adherence

Sponsors and collaborators

Lead sponsor

National University of Singapore

Other

Collaborators

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

Registry information

Acronym: CRESCENT

Important dates

Study start
2019
Primary completion
2023
Study completion
2024
First posted
Oct 9, 2019
Registry last updated
Feb 20, 2024

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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