Obstructive Sleep Apnea
Conditions
Keywords
Obstructive Sleep Apnea, Ventilatory Control Instability, Complex Sleep Apnea
Brief summary
The current study combines two treatments for obstructive sleep apnea (OSA), oral appliances and supplemental inspired oxygen. The following aims will be tested: Aim 1. To determine whether supplemental inspired oxygen further reduces OSA severity (apnea-hypopnea index) in patients using an oral appliance. Aim 2. To determine whether baseline OSA phenotypes can predict the efficacy of oral appliances versus supplemental oxygen versus both treatments in combination. We will test whether responders to oral appliances have distinct pathophysiological characteristics compared with oxygen responders.
Detailed description
Pre-specified primary analysis for Aim 1 is the change in AHI with combination treatment versus oral appliance alone (%reduction versus placebo; including hypopnea events without desaturation/arousals). Aim 2 seeks to identify subgroups of patients that have the greatest reduction in AHI (responders) with each treatment (post-hoc). We will use baseline physiological measures of the four traits causing OSA (collapsibility, responsiveness, loop gain, arousal threshold) to determine which characteristics predict responses to each intervention (leave-one-out support vector machine modeling). Clinical measures of the same traits will be estimated from the placebo night to confirm that responses can be predicted with clinically-available data. We will also test whether responders to oral appliances have a greater response to oxygen than oral appliance non-responders (and vice-versa), to address whether responders to both treatments are similar or different.
Interventions
DEVICEOral appliance
An oral appliance (dental mouthpiece) will be used to improve upper airway patency. Patients who do not have their own custom dental oral appliance (various brands, commonly Herbst/Somnomed) will be provided with a device (BluePro, BlueSom) for the duration of the study. Patients will also be administered sham (room air) at 4 L/min via nasal cannula.
DRUGOxygen
Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.
OTHEROral appliance plus oxygen
Both treatments will be administered simultaneously.
OTHERNo treatment
Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.
Sponsors
Monash University
American Heart Association
National Heart, Lung, and Blood Institute (NHLBI)
Heart Foundation of Australia
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Supplemental oxygen versus air assignment nights will be blinded to participants, but will be known by the investigator. Oral appliances will be open label.
Intervention model description
Subjects will receive mandibular advancement, supplemental oxygen, mandibular advancement plus supplemental oxygen, and no treatment in randomized order. On nights without supplemental oxygen, subjects will be administered sham (air, single blinded). Oral appliance use will not be masked.
Eligibility
Sex/Gender
ALL
Age
21 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed OSA or suspected OSA based on snoring
Exclusion criteria
* Severe co-morbidities (cardiovascular, renal, lung disease, neurological), including: Congestive heart failure, Neurological conditions that may affect sleep or breathing (e.g. neuromuscular diseases e.g. myasthenia gravis; neurodegenerative diseases e.g. Alzheimer's/Parkinson's) * Medications that will substantially affect respiration, including opioids, barbiturates, theophylline, doxapram, acetazolamide, pseudoephedrine * Claustrophobia * Insomnia and other non-respiratory sleep disorders * Inability to sleep supine * Contraindications to oral appliances, including insufficient teeth to support the device, periodontal problems inducing tooth mobility, active temporomandibular joint disorder * Allergy to lidocaine or oxymetazoline HCl
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in apnea hypopnea index (AHI), percent of baseline. | Single night | Primary test is difference between combination therapy and oral appliance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in frequency of arousals, percent of baseline. | Single night | Primary test is difference between combination therapy and oral appliance |
| Patient reported sleep quality (visual analog scale) | Single night | Primary test is difference between combination therapy and oral appliance |
| Morning minus evening systolic blood pressure | Single night | Primary test is difference between combination therapy and oral appliance |
| Morning minus evening diastolic blood pressure | Single night | Primary test is difference between combination therapy and oral appliance |
Countries
Australia, United States
Outcome results
None listed