Clinical trial NCT04021810: Combination Therapy Associating CPAP and Mandibular Advancement Device in OSA
Official title: Combination Therapy Associating CPAP and Mandibular Advancement Device ( MAD) in Obstructive Sleep Apnea (OSA) Low CPAP Compliers: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Obstructive Sleep Apnea Syndrome
Hypertension
Keywords: Sleep Apnea
CPAP
Mandibular Advancement Device
Arterial Hypertension
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: ONIRIS
First posted: 2019-07-16
Enrollment: 5
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Nightime Mean Blood Pressure
timeFrame: 3 months
Secondary outcomes:
measure: Other 24h ambulatory blood pressure measurements
timeFrame: 3 months
measure: Blood Pressure Variability
timeFrame: 3 months
measure: Percent Dippers/dipping phenotypes
timeFrame: 3 months
measure: 3-days home Blood Pressure measurements (systolic, diastolic)
timeFrame: 3 months
measure: Epworth Score
timeFrame: 3 months
measure: Quality of Life score
timeFrame: 3 months
measure: Serum concentration of Cholesterol
timeFrame: 3 months
measure: Serum concentration of Triglycerides
timeFrame: 3 months
measure: Concentration of fasting Glucose
timeFrame: 3 months
measure: Amount of HbA1C
timeFrame: 3 months
measure: Incidence of adverse events related to the treatment
timeFrame: 3 months
measure: Compliance to treatment(s)
timeFrame: 3 months
measure: Efficacy determined by comparison of Apnea-Hypopnea Index (AHI), number of central and obstructive apneas and hypopneas, before and after treatment
timeFrame: 3 months
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Nouvelle Clinique Bel Air
city: Grenoble
country: France
facility: University Hospital Grenoble
city: Montpellier
country: France
facility: University Hospital Montpellier
city: Perpignan
country: France
facility: Cabinet Médical
Study officials:
affiliation: University Hospital, Grenoble
name: Jean-Louis Pépin, Pr, PhD
role: PRINCIPAL_INVESTIGATOR
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