Clinical trial NCT03189173: Combined Upper-airway and Breathing Control Therapies for Obstructive Sleep Apnea
Official title: Combined Upper-airway and Breathing Control Therapies for Obstructive Sleep Apnea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obstructive Sleep Apnea
Keywords: Obstructive Sleep Apnea
Ventilatory Control Instability
Complex Sleep Apnea
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Monash University
name: American Heart Association
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Heart Foundation of Australia
First posted: 2017-06-16
Enrollment: 41
Sex: ALL
Minimum age (years): 21
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in apnea hypopnea index (AHI), percent of baseline.
timeFrame: Single night
Secondary outcomes:
measure: Change in frequency of arousals, percent of baseline.
timeFrame: Single night
measure: Patient reported sleep quality (visual analog scale)
timeFrame: Single night
measure: Morning minus evening systolic blood pressure
timeFrame: Single night
measure: Morning minus evening diastolic blood pressure
timeFrame: Single night
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Notting Hill
country: Australia
facility: Sleep and Circadian Medicine Laboratory, BASE Facility, Monash University
state: Victoria
Study officials:
affiliation: Brigham and Women's Hospital
name: Scott A Sands, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Monash University
name: Bradley A Edwards, PhD
role: PRINCIPAL_INVESTIGATOR
References: