Combination Therapy Associating CPAP and Mandibular Advancement Device in OSA

Study Overview
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Brief Summary
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The aim of this study is to evaluate the efficacy of a combination of Continuous Positive Airway Pressure (CPAP) and a Mandibular Advancement Device (MAD) on nocturnal Blood Pressure control in hypertensive patients in obstructive sleep apnea low CPAP compliers (less than 4 hours per night). Hypertensive patients demonstrating low CPAP adherence will be selected during a screening visit; they will be then randomized to one of the three following arms: Education to CPAP (CPAP only), Treatment by a MAD (MAD only) or a combination of both CPAP and MAD (CPAP+MAD). Mean systolic, diastolic, diurnal and nocturnal blood pressure will be assessed during 24-h Ambulatory Blood Pressure monitoring, before and after a 3-month treatment intervention. Biological laboratory parameters, patients reported outcomes (daytime sleepiness and Quality of Life), will also be evaluated before and after 3 months of treatment.

Detailed Description
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The aim of this study is to test the efficacy of a combination of Continuous Positive Airway Pressure (CPAP) treatment and a Mandibular Advancement Device (MAD) on the control of nocturnal Blood Pressure over a 3-month period in hypertensive obstructive sleep apnea being low CPAP compliers. This is a prospective, randomized, open-label and multi-centric study. The investigators plan to include 105 hypertensive patients demonstrating low CPAP adherence (less than 4 hours per night). Patients will be randomly assigned to one of the following treatments: Education for improving CPAP adherence ('CPAP Only' group: patients will continue their CPAP treatment and be supported by regular coaching aimed at increasing their compliance to treatment); Mandibular Advancement Device ('MAD Only' group: patients will switch their treatment from CPAP to a MAD); a combination of CPAP and MAD ('CPAP + MAD' group: patients will be treated by both devices used simultaneously). The duration of the study is 3 months. At the selection visit, patients will undergo a polysomnography/respiratory polygraphy followed by 24h- Ambulatory Blood Pressure Monitoring, PROMs (Quality of Life, Epworth Sleepiness Score) and a blood sample for biological parameters analysis. Patients will be then randomized to one of the three groups. Patients assigned to the 'CPAP only group' will be contacted by the homecare provider to arrange coaching sessions in order to improve their compliance to CPAP (phone calls and/or home visits). Patients assigned to the 'MAD Only group' will be proposed a Mandibular Advancement Device. Patients assigned to the 'CPAP+MAD group' will have both CPAP (with coaching) and a MAD. After a 3-month treatment period, the same measurements (24h-Ambulatory Blood pressure, polysomnography/respiratory polygraphy, questionnaires, and blood sample analysis) will be repeated to compare efficacy of the 3 interventions. Tolerance (number of adverse events) and adherence to treatments will also be assessed. The 'CPAP+MAD' group will be compared to the other two groups in order to evaluate the benefit of the combination therapy.

Official Title
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Combination Therapy Associating CPAP and Mandibular Advancement Device ( MAD) in Obstructive Sleep Apnea (OSA) Low CPAP Compliers: A Randomized Controlled Trial

Conditions
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Obstructive Sleep Apnea Syndrome, Hypertension

Intervention / Treatment
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* Device: Continuous Positive Airway Pressure (CPAP) and patient education
* Device: Mandibular Advancement Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Arterial Hypertension (Clinical Blood Pressure > 140/90 mmHg or patient under medication with nocturnal hypertension seen in the Ambulatory Blood Pressure Measurement) Severe obstructive sleep apnea syndrome, treated by CPAP for more than 6 months and less than 5 years, with a compliance <4h/night No contraindication to a treatment by Mandibular Advancement Device Ability to understand study procedures and signed informed consent Covered by French social security system or equivalent Exclusion Criteria: Central Obstructive Apnea (>20% Central Apneas/Hypopneas) Pregnant or breastfeeding womens Prisoners or persons who require protection by the law Persons within the exclusion period of another study Contraindication to a mandibular advancement device (oral-dental pathology, pathology of the temporo-mandibular articulation, poor periodontal status)

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CPAP only<br>Obstructive sleep apnea patients with CPAP treatment only | Device: Continuous Positive Airway Pressure (CPAP) and patient education<br>* Mask connected to a pump (CPAP machine) that forces air into the nasal passages at pressures high enough to overcome obstructions in the airways. Plus patient education.<br>|
| Active Comparator: Mandibular Advancement Device only<br>Obstructive sleep apnea patients with Mandibular Advancement Device only | Device: Mandibular Advancement Device<br>* Adjustable oral prosthesis which retains the lower mandible in an anterior position, thus limiting sleep apneas<br>|
| Experimental: CPAP + Mandibular Advancement Device<br>Obstructive sleep apnea patients with combined CPAP and Mandibular Advancement Device | Device: Continuous Positive Airway Pressure (CPAP) and patient education<br>* Mask connected to a pump (CPAP machine) that forces air into the nasal passages at pressures high enough to overcome obstructions in the airways. Plus patient education.<br>Device: Mandibular Advancement Device<br>* Adjustable oral prosthesis which retains the lower mandible in an anterior position, thus limiting sleep apneas<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nightime Mean Blood Pressure | Difference in nighttime Mean Blood Pressure before and after treatment, measured by ambulatory blood pressure | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Other 24h ambulatory blood pressure measurements | 24h ambulatory blood pressure measurements (systolic, diastolic and mean, diurnal and nocturnal) before and after treatment | 3 months | 
| Blood Pressure Variability | Blood Pressure variability before and after treatment, measured by ambulatory blood pressure measurements | 3 months | 
| Percent Dippers/dipping phenotypes | Percentage of dipper patients (>10% drop in nocturnal Blood Pressure compared with daytime BP) | 3 months | 
| 3-days home Blood Pressure measurements (systolic, diastolic) | self-measurement of Systolic and Diastolic Blood Pressure, measured over 3 days, twice a day, before and after interventions | 3 months | 
| Epworth Score | Score on the Epworth Sleepiness Questionnaire, before and after treatment. The ESS is a self-administered questionnaire with 8 questions. Patients are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 sub-item scores( 0-3) can range from 0 to 24. The higher the ESS score the greater the likelihood that the person has daytime sleepiness. | 3 months | 
| Quality of Life score | Score on the Quality Of Life Questionnaire SF12, before and after treatment. The SF-12 is a self-administered short survey with 12 questions assessing quality of life. The questions are combined, scored, and weighted to create two subscales (mental and social score and physical score) that provide glimpses into health-related quality of life. The lower the scores the more disability. | 3 months | 
| Serum concentration of Cholesterol | Serum concentration of low-density lipoprotein cholesterol (LPL-C) and high-density lipoprotein cholesterol (HDL-C), before and after treatment. | 3 months | 
| Serum concentration of Triglycerides | Serum concentration of Triglyceride, before and after treatment | 3 months | 
| Concentration of fasting Glucose | Concentration of fasting glucose, before and after treatment | 3 months | 
| Amount of HbA1C | Amount of HbA1c, before and after treatment | 3 months | 
| Incidence of adverse events related to the treatment | Number of adverse events related to the treatment during the 3-month period | 3 months | 
| Compliance to treatment(s) | Use of the device(s) defined by number of hour per night and number of night per week | 3 months | 
| Efficacy determined by comparison of Apnea-Hypopnea Index (AHI), number of central and obstructive apneas and hypopneas, before and after treatment | AHI, central and obstructive apneas and hyponeas index, measured by polysomnography or polygraphy, before and after treatment | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep Apnea, CPAP, Mandibular Advancement Device, Arterial Hypertension