Adherence and Preference of Continuous Positive Airway Pressure Versus Mandibular Advancement Splints in Obstructive Sleep Apnea Patients: A Randomized Trial

Study Overview
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Brief Summary
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Obstructive sleep apnea (OSA) is a major health problem affecting over 1,000,000 Canadians. It is the cause of significant healthcare costs with increased morbidity and mortality. The two most common and effective therapies used to treat OSA are: (1) Continuous or Automatic Positive Airway Pressure (PAP), and (2) Mandibular Advancement Splints (MAS). While both therapies reduce upper airway collapse during sleep, they differ in efficacy, acceptance, cost and side-effects, but surprisingly are similar in improving quality of life, sleepiness and blood pressure. PAP is more effective in reducing apneas while MAS is easier to use. Until now, studies have used self-reported adherence data on MAS versus objective adherence on PAP. Many studies have hypothesized that the sub-optimal efficacy with MAS therapy is counterbalanced by the superior adherence relative to PAP, resulting in a similar effectiveness for both treatments. Compliance smart chips are a recent innovation for MAS and could be used to prove this hypothesis and allow a new and complete comparison of effectiveness (efficacy + adherence) between MAS and PAP. Understanding the patient's objective adherence and long-term symptomatic improvement would provide vital information to doctors and dentists in choosing the right treatment for patients. Sixty OSA patients will receive both PAP and MAS in a random sequence. This innovative study lead by two experienced new investigators, and a research team of multidisciplinary experts, will assess objective adherence, treatment efficacy, patient preference, sleepiness and quality of life of each treatment used at home for 1 month per treatment. After this, patients will be able to go back and forth between both treatments during an additional 6-month period. The results of this study will be used by healthcare policy makers as well as clinicians who need to be part of the treatment plan decision for the many Canadians who suffer from sleep apnea.

Detailed Description
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The primary aim of this study is to assess objective adherence to treatment, for PAP and MAS, and to evaluate if there will be similar effectiveness (efficacy+adherence) between PAP and MAS treatment for patients with mild to severe OSA. The secondary aim is to assess if patient preference does correlate to the final treatment adherence. An exploratory aim is to assess if the strategy of patients having both treatments available to use interchangeably could further improve treatment adherence, sleepiness, quality of life and fatigue. Having a better insight into patient adherence will improve the cost-effectiveness of treatment and will improve the health and quality of life for many Canadians who suffer from sleep apnea. The proposed trial is a randomized open-label, two-treatment, two-period cross-over trial followed by an observational trial. Sixty OSA patients (10≤AHI≤50) will receive both PAP and MAS. As a recent innovation, we have adherence monitors for MAS that can give a new and comprehensive comparative analysis of the effectiveness between MAS and PAP. In the randomized trial phase the two treatments will be used separately for 1 month each (after treatment adaptation/titration of 1-2 months for each device). Treatment efficacy and daily treatment use data will be assessed together with changes in symptoms (quality of life, sleepiness and fatigue). Patient initial preference will be determined by using a patient decision aid. This will be followed by the observational trial phase, where all patients will have access to both interventions at home for 6 months and be allowed to choose on a daily basis the intervention to use. The intervention duration of 6 months is to allow for a sustained response in long-term adherence and to observe changes in quality of life.

Official Title
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Adherence and Preference of Continuous Positive Airway Pressure Versus Mandibular Advancement Splints in Obstructive Sleep Apnea Patients: A Randomized Trial

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Device: Positive Airway Pressure (PAP)
* Device: Mandibular Advancement Splints (MAS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: You may be able to participate in this study if: You are naïve to treatment (never used CPAP or oral appliance, nor had surgery for sleep apnea); You are between 19-75 years old; You have a Body Mass Index (BMI) ≤ 35; You have enough teeth (at least 8 per arch) for MAS; You have: an Apnea-Hypopnea Index (AHI) within the range 10 ≤ AHI ≤ 50 documented with polysomnography in the last 2 years; ***OR*** a Respiratory Disturbance Index (RDI) within the range 20 ≤ RDI ≤ 50 documented with level III portable sleep test; ***OR*** an Oxygen Desaturation Index (ODI) ≥ 10; and You have had a sleep test within the past 2 years. Exclusion Criteria: You may not be able to participate in this study if: You have extensive periodontal disease with significant tooth mobility (disease around your teeth); You are unable to protrude the jaw (unable to extend your jaw); You have a lack of a sufficient vertical opening to accommodate an appliance; You have uncontrolled congestive heart failure (defined as a prior clinical diagnosis, an ejection cutoff of 40% or a clinical sign in the opinion of a primary care physician or cardiologist) that makes it unsafe for you to participate in the trial in the opinion of the investigators; You have coronary artery disease unless stable for at least 6 months and considered by the investigators to have a stable disease; You have a history of angina (chest pain when your heart does not get enough blood), myocardial infarction (heart attack) or stroke; You have a history of major depressive disorder (such as bipolar disorder) along with current moderate or severe disease; You have cancer unless in remission (decreasing signs of your cancer being present) for more than 1 year; You have known renal (kidney) failure with need for dialysis; You are pregnant (if a female participant becomes pregnant during the trial, she will be withdrawn from the study); You have had a near miss or prior automobile accident due to sleepiness within the past 12 months; and/or At nighttime, 30% of the night is at ≤ 90% oxygen saturation levels.

Ages Eligible for Study
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Minimum Age: 19 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MAS-PAP<br>Mandibular advancement splints (MAS): dental splints used to keep the mandible in an advanced position opening the upper airway during sleep; followed by positive airway pressure (PAP) | Device: Positive Airway Pressure (PAP)<br>* Continuous or auto-adjusting positive airway pressure (i.e. CPAP, APAP, and described here as PAP): a device which consists of a face mask attached to a plastic tube and a machine that blows compressed air through a patient's airway during sleep to keep the airway open<br>* Other names: CPAP, auto-CPAP, APAP;Device: Mandibular Advancement Splints (MAS)<br>* Mandibular advancement splints (MAS): dental splints used to keep the mandible in an advanced position opening the upper airway during sleep<br>* Other names: Somnodent device;|
| Active Comparator: PAP-MAS<br>Positive airway pressure (PAP): a device which consists of a face mask attached to a plastic tube and a machine that blows compressed air through a patient's airway during sleep to keep the airway open; followed by mandibular advancement splints (MAS) | Device: Positive Airway Pressure (PAP)<br>* Continuous or auto-adjusting positive airway pressure (i.e. CPAP, APAP, and described here as PAP): a device which consists of a face mask attached to a plastic tube and a machine that blows compressed air through a patient's airway during sleep to keep the airway open<br>* Other names: CPAP, auto-CPAP, APAP;Device: Mandibular Advancement Splints (MAS)<br>* Mandibular advancement splints (MAS): dental splints used to keep the mandible in an advanced position opening the upper airway during sleep<br>* Other names: Somnodent device;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objectively measured adherence (hours/night and nights/week of intervention use). | Measuring objective adherence (hours/night and nights/week of intervention use), indicated by the smart chips and symptoms. | At 1 month in the MAS treatment arm | 
| Objectively measured adherence (hours/night and nights/week of intervention use). | Measuring changes in objectively measured adherence (hours/night and nights/week of intervention use), indicated by the smart chips and symptoms. | At 1 month in CPAP treatment arm | 
| Objectively measured adherence (hours/night and nights/week of intervention use). | Measuring changes in objectively measured adherence (hours/night and nights/week of intervention use), indicated by the smart chips and symptoms. | At 1 month of using both treatments interchangeably. | 
| Objectively measured adherence (hours/night and nights/week of intervention use). | Measuring changes in objectively measured adherence (hours/night and nights/week of intervention use), indicated by the smart chips and symptoms. | At 6 months of using both treatments interchangeably | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apnea-hypopnea index | Measuring apnea-hypopnea index (events/hour of sleep from Stardust-Phillips Respironics) to measure intervention efficacy (e.g. AHI) | At baseline | 
| Functional Outcomes of Sleep Questionnaire (FOSQ) responses | Measuring Functional Outcomes of Sleep Questionnaire (FOSQ) responses to evaluate disease specific quality of life. | At baseline | 
| Epworth Sleepiness Scale (ESS) questionnaire responses. | Measuring responses to Epworth Sleepiness Scale (ESS) Questionnaire to compare daytime sleepiness. | At baseline | 
| Chalder fatigue scale questionnaire responses | Measuring responses to the Chalder fatigue scale which assesses fatigue in the present state. | At baseline | 
| SF-36 survey responses | Measuring SF-36 survey responses which assesses general health status. | At baseline | 
| Apnea-hypopnea index | Measuring changes in apnea-hypopnea index (events/hour of sleep from Stardust-Phillips Respironics) to measure intervention efficacy (e.g. AHI) | At 1 month in MAS treatment arm | 
| Apnea-hypopnea index | Measuring changes in apnea-hypopnea index (events/hour of sleep from Stardust-Phillips Respironics) to measure intervention efficacy (e.g. AHI) | At 1 month in CPAP treatment arm | 
| Functional Outcomes of Sleep Questionnaire (FOSQ) responses. | Measuring changes in Functional Outcomes of Sleep Questionnaire (FOSQ) responses to evaluate disease specific quality of life. | At 1 month in MAS treatment arm | 
| Functional Outcomes of Sleep Questionnaire (FOSQ) responses. | Measuring changes in Functional Outcomes of Sleep Questionnaire (FOSQ) responses to evaluate disease specific quality of life. | At 1 month of using both treatments interchangeably | 
| Functional Outcomes of Sleep Questionnaire (FOSQ) responses | Measuring changes in Functional Outcomes of Sleep Questionnaire (FOSQ) responses to evaluate disease specific quality of life. | At 6 months of using both treatments interchangeably | 
| Functional Outcomes of Sleep Questionnaire (FOSQ) responses. | Measuring changes in Functional Outcomes of Sleep Questionnaire (FOSQ) responses to evaluate disease specific quality of life. | At 1 month in CPAP treatment arm | 
| Epworth Sleepiness Scale (ESS) questionnaire responses. | Measuring changes in Epworth Sleepiness Scale (ESS) Questionnaire responses to compare daytime sleepiness. | At 1 month in MAS treatment arm | 
| Epworth Sleepiness Scale (ESS) questionnaire responses. | Measuring changes in responses to Epworth Sleepiness Scale (ESS) Questionnaire to compare daytime sleepiness | At 1 month in CPAP treatment arm. | 
| Epworth Sleepiness Scale (ESS) questionnaire responses | Measuring changes in responses to Epworth Sleepiness Scale (ESS) Questionnaire to compare daytime sleepiness. | At 1 month of using both treatments interchangeably | 
| Epworth Sleepiness Scale (ESS) questionnaire responses. | Measuring changes in responses to Epworth Sleepiness Scale (ESS) Questionnaire to compare daytime sleepiness. | At 6 months of using both treatments interchangeably. | 
| Chalder fatigue scale questionnaire responses | Measuring changes in responses to the Chalder fatigue scale which assesses fatigue in the present state. | At 1 month in MAS treatment arm | 
| Chalder fatigue scale questionnaire responses | Measuring changes in responses to the Chalder fatigue scale which assesses fatigue in the present state. | At 1 month in CPAP treatment arm | 
| Chalder fatigue scale questionnaire responses | Measuring changes in responses to the Chalder fatigue scale which assesses fatigue in the present state. | At 1 month of using both treatments interchangeably | 
| Chalder fatigue scale questionnaire responses | Measuring changes in responses to the Chalder fatigue scale which assesses fatigue in the present state. | At 6 months of using both treatments interchangeably. | 
| SF-36 survey responses. | Measuring changes in SF-36 survey responses which assesses general health status. | At 1 month in MAS treatment arm | 
| SF-36 survey responses. | Measuring changes in SF-36 survey responses which assesses general health status. | At 1 month in CPAP treatment arm. | 
| SF-36 survey responses. | Measuring changes in SF-36 survey responses which assesses general health status. | At 1 month of using both treatments interchangeably. | 
| SF-36 survey responses. | Measuring changes in SF-36 survey responses which assesses general health status. | At 6 months of using both treatments interchangeably. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adherence, CPAP, Oral Appliance, Mandibular Advancement Splints, Preference