Combination Therapy Associating CPAP and Mandibular Advancement Device in OSA

Hypertension Clinical Trial

— PPC-OAM  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04021810
• Other study ID #: 38RC17.350
• Status: Terminated
• Phase: N/A
• Start date: November 18, 2019
• Est. completion date: May 18, 2021

Study information

• Verified date: May 2022
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: May 18, 2021
• Est. primary completion date: March 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Apnea
• Hypertension
• Obstructive Sleep Apnea Syndrome
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Device:
• Continuous Positive Airway Pressure (CPAP) and patient education
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.
• Mandibular Advancement Device
Adjustable oral prosthesis which retains the lower mandible in an anterior position, thus limiting sleep apneas

Locations

Country	Name	City	State
France	Nouvelle Clinique Bel Air	Bordeaux
France	University Hospital Grenoble	Grenoble
France	University Hospital Montpellier	Montpellier
France	Cabinet Médical	Perpignan

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Grenoble	ONIRIS

Country where clinical trial is conducted

France, 

References & Publications (11)

Bailly S, Destors M, Grillet Y, Richard P, Stach B, Vivodtzev I, Timsit JF, Lévy P, Tamisier R, Pépin JL; scientific council and investigators of the French national sleep apnea registry (OSFP). Obstructive Sleep Apnea: A Cluster Analysis at Time of Diagn — View Citation

Bratton DJ, Gaisl T, Schlatzer C, Kohler M. Comparison of the effects of continuous positive airway pressure and mandibular advancement devices on sleepiness in patients with obstructive sleep apnoea: a network meta-analysis. Lancet Respir Med. 2015 Nov;3 — View Citation

Bratton DJ, Gaisl T, Wons AM, Kohler M. CPAP vs Mandibular Advancement Devices and Blood Pressure in Patients With Obstructive Sleep Apnea: A Systematic Review and Meta-analysis. JAMA. 2015 Dec 1;314(21):2280-93. doi: 10.1001/jama.2015.16303. Review. — View Citation

Kendzerska T, Gershon AS, Hawker G, Leung RS, Tomlinson G. Obstructive sleep apnea and risk of cardiovascular events and all-cause mortality: a decade-long historical cohort study. PLoS Med. 2014 Feb 4;11(2):e1001599. doi: 10.1371/journal.pmed.1001599. eC — View Citation

Lévy P, Kohler M, McNicholas WT, Barbé F, McEvoy RD, Somers VK, Lavie L, Pépin JL. Obstructive sleep apnoea syndrome. Nat Rev Dis Primers. 2015 Jun 25;1:15015. doi: 10.1038/nrdp.2015.15. Review. — View Citation

Malhotra A, Orr JE, Owens RL. On the cutting edge of obstructive sleep apnoea: where next? Lancet Respir Med. 2015 May;3(5):397-403. doi: 10.1016/S2213-2600(15)00051-X. Epub 2015 Apr 14. Review. — View Citation

Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005 Mar 19-25;365(9464):1046- — View Citation

Mokhlesi B, Hagen EW, Finn LA, Hla KM, Carter JR, Peppard PE. Obstructive sleep apnoea during REM sleep and incident non-dipping of nocturnal blood pressure: a longitudinal analysis of the Wisconsin Sleep Cohort. Thorax. 2015 Nov;70(11):1062-9. doi: 10.11 — View Citation

Pépin JL, Tamisier R, Baguet JP, Lepaulle B, Arbib F, Arnol N, Timsit JF, Lévy P. Fixed-pressure CPAP versus auto-adjusting CPAP: comparison of efficacy on blood pressure in obstructive sleep apnoea, a randomised clinical trial. Thorax. 2016 Aug;71(8):726 — View Citation

Pépin JL, Tamisier R, Barone-Rochette G, Launois SH, Lévy P, Baguet JP. Comparison of continuous positive airway pressure and valsartan in hypertensive patients with sleep apnea. Am J Respir Crit Care Med. 2010 Oct 1;182(7):954-60. doi: 10.1164/rccm.20091 — View Citation

Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993 Apr 29;328(17):1230-5. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nightime Mean Blood Pressure	Difference in nighttime Mean Blood Pressure before and after treatment, measured by ambulatory blood pressure	3 months
Secondary	Other 24h ambulatory blood pressure measurements	24h ambulatory blood pressure measurements (systolic, diastolic and mean, diurnal and nocturnal) before and after treatment	3 months
Secondary	Blood Pressure Variability	Blood Pressure variability before and after treatment, measured by ambulatory blood pressure measurements	3 months
Secondary	Percent Dippers/dipping phenotypes	Percentage of dipper patients (>10% drop in nocturnal Blood Pressure compared with daytime BP)	3 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Serum concentration of Triglycerides	Serum concentration of Triglyceride, before and after treatment	3 months
Secondary	Concentration of fasting Glucose	Concentration of fasting glucose, before and after treatment	3 months
Secondary	Amount of HbA1C	Amount of HbA1c, before and after treatment	3 months
Secondary	Incidence of adverse events related to the treatment	Number of adverse events related to the treatment during the 3-month period	3 months
Secondary	Compliance to treatment(s)	Use of the device(s) defined by number of hour per night and number of night per week	3 months
Secondary	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