Impact of the Mandibular Advancement Device on Sleep Apnea During CPAP Withdrawal

Study Overview
=================
Brief Summary
-----------------
Obstructive sleep apnea hypopnea syndrome (OSAS) is a frequent disease with neuropsychological and cardiovascular (CV) consequences. Continuous positive pressure (CPAP), the main treatment for OSAHS, is effective on the majority of symptoms but restrictive, which can promote non-compliance. Treatment interruptions are often observed in connection with intercurrent events such as nasal obstructions or even when patients are on the move. However, randomized trials have shown that stopping treatment, even for a short time, leads to a recurrence of symptoms and significant CV disturbances (increase in blood pressure, endothelial dysfunction, cardiac repolarization disorders). It seems important to consider strategies that promote therapeutic continuity. The mandibular advancement device (MAD) is an interesting tool in this regard. MAD is as effective as CPAP on symptoms and CV data. The investigators want to assess its effectiveness as a complementary treatment during treatment discontinuation on the main consequences of OSAHS.

Detailed Description
-----------------
Patients are recruited during sleep consultations in the Angers University Hospital pneumology department among patients followed for severe OSAHS and treated with CPAP. All of the scheduled examinations are carried out in the sleep laboratory of the CHU d'Angers. Patients meeting the inclusion criteria and not having any non-inclusion criteria are randomized to the MAD group or to the control group. For patients in the MAD group, an appointment with a stomatologist is organized to make and adjust a thermo-molded type MAD. An initial assessment is carried out for all patients during a day hospitalization specific to the study (study of endothelial function, blood pressure, Osler test, ECG, venous and urinary sampling, and completion of the study questionnaires). Patients are then asked to stop CPAP treatment for two weeks. Patients in the OAM group use OAM during this period. Patients in the control group do not receive any specific treatment for their OSAHS during this period. After 2 weeks of stopping CPAP, a second assessment, identical to the initial assessment, is carried out for all patients. This assessment is carried out during one night of hospitalization which also allows a PSG to be carried out under OAM or without treatment. At the end of this assessment, the study is terminated and the patients resume their usual use of CPAP.

Official Title
-----------------
Impact of the Mandibular Advancement Device on Sleep Apnea Syndrome During Discontinuation of Treatment With Continuous Positive Airway Pressure: Randomized Controlled Trial

Conditions
-----------------
Sleep Apnea, Obstructive, Endothelial Dysfunction

Intervention / Treatment
-----------------
* Device: Mandibular advancement device treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient accepting MAD treatment Patient with an apnea-hypopnea index (AHI) greater than 30 events per hour on the initial recording Patient with excessive daytime sleepiness during initial treatment (ESE>10) Patient treated for more than 12 months by CPAP with average compliance greater than 5 hours per night Exclusion Criteria: Initial severe daytime sleepiness characterized OSAS with ≥ 5 central apneas per hour of sleep at baseline recording Previously diagnosed severe cardiac and/or respiratory pathology: Body mass index ≥ 35 kg/m2 Known contraindication to OAM treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: control group<br>Patients will be ask not to use any OSAS treatment during the 2 weeks of the study (after the CPAP withdrawal) | |
| Experimental: mandibular advancement device<br>Patients will be asked to use mandibular advancement device during the 2 weeks CPAP withdrawal | Device: Mandibular advancement device treatment<br>* a titratable thermoplastic mandibular advancement device will be proposed to patient in the experimental group during the 2 weeks of CPAP withdrawal.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in subjective sleepiness | Sleepiness assessed using the Epworth Sleepiness Scale | before and two weeks after CPAP withdrawal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in objective sleepiness | Osler test | before and two weeks after CPAP withdrawal | 
| Change in subjective sleep quality | Pittsburgh sleep quality index | before and two weeks after CPAP withdrawal | 
| Change in executive function | trail making test | before and two weeks after CPAP withdrawal | 
| Change in 24 hour blood pressure | 24 hours systolic, diastolic and mean blood pressure (Blood pressure holter) | before and two weeks after CPAP withdrawal | 
| Change in endothelial function | endothelial function (assessed by reactive hyperemia arterial tonometry) | before and two weeks after CPAP withdrawal | 
| Change in cardiac repolarization | cardiac repolarization (QTc, TpTec intervals calculation on electrocardiographe)) | before and two weeks after CPAP withdrawal | 
| Change in catecholamines levels | urine catecholamines levels | before and two weeks after CPAP withdrawal | 
| Change in glucose levels | blood glucose levels | before and two weeks after CPAP withdrawal | 
| Change in Microparticles | blood microparticles levels | before and two weeks after CPAP withdrawal | 
| Change in oxydative stress | blood 8-isoprostane levels | before and two weeks after CPAP withdrawal | 
| Change in inflammation | blood CRPus levels | before and two weeks after CPAP withdrawal |