Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 15SDG25890059 | Other Grant/Funding Number | American Heart Association | |
| R01HL128658 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Monash University | OTHER |
| American Heart Association | OTHER |
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| Heart Foundation of Australia |
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Combo, Mad, Sham, Oxygen | Experimental | Order of interventions: Combo, Mad, Sham, Oxygen |
|
| Combo, Oxygen, Mad, Sham | Experimental | Order of interventions: Combo, Oxygen, Mad, Sham |
|
| Combo, Oxygen, Sham, MAD | Experimental | Order of interventions: Combo, Oxygen, Sham, MAD |
|
| Combo, Sham, Mad, Oxygen | Experimental | Order of interventions: Combo, Sham, Mad, Oxygen |
|
| Combo, Sham, Oxygen, MAD | Experimental | Order of interventions: Combo, Sham, Oxygen, MAD |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral appliance | Device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in apnea hypopnea index (AHI), percent of baseline. | Primary test is difference between combination therapy and oral appliance | Single night |
| Measure | Description | Time Frame |
|---|---|---|
| Change in frequency of arousals, percent of baseline. | Primary test is difference between combination therapy and oral appliance | Single night |
| Patient reported sleep quality (visual analog scale) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
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)
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Scott A Sands, PhD | Brigham and Women's Hospital | Principal Investigator |
| Bradley A Edwards, PhD | Monash University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States | ||
| Sleep and Circadian Medicine Laboratory, BASE Facility, Monash University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39688178 | Derived | Hynes DJ, Mann DL, Landry SA, Joosten SA, Edwards BA, Hamilton GS. Night-to-night variability in obstructive sleep apnea severity, the physiological endotypes, and the frequency of flow limitation. Sleep. 2025 Apr 11;48(4):zsae295. doi: 10.1093/sleep/zsae295. |
Not provided
Not provided
Deidentified subject data will be shared via an online repository.
Not provided
6 months after publication
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D020181 | Sleep Apnea, Obstructive |
| D012891 | Sleep Apnea Syndromes |
| ID | Term |
|---|---|
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D020919 | Sleep Disorders, Intrinsic |
Not provided
Not provided
| ID | Term |
|---|---|
| D017090 | Occlusal Splints |
| D010100 | Oxygen |
| D003131 | Combined Modality Therapy |
| C005703 | salicylhydroxamic acid |
| ID | Term |
|---|---|
| D009989 | Orthotic Devices |
| D009983 | Orthopedic Equipment |
| D013523 | Surgical Equipment |
| D004864 | Equipment and Supplies |
Not provided
Not provided
| UNKNOWN |
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.
Not provided
Not provided
Supplemental oxygen versus air assignment nights will be blinded to participants, but will be known by the investigator. Oral appliances will be "open label".
| MAD, Combo, Oxygen, Sham | Experimental | Order of interventions: MAD, Combo, Oxygen, Sham |
|
| MAD, Combo, Sham, Oxygen | Experimental | Order of interventions: MAD, Combo, Sham, Oxygen |
|
| MAD, Oxygen, Combo, Sham | Experimental | Order of interventions: MAD, Oxygen, Combo, Sham |
|
| MAD, Oxygen, Sham, Combo | Experimental | Order of interventions: MAD, Oxygen, Sham, Combo |
|
| MAD, Sham, Combo, Oxygen | Experimental | Order of interventions: MAD, Sham, Combo, Oxygen |
|
| MAD, Sham, Oxygen, Combo | Experimental | Order of interventions: MAD, Sham, Oxygen, Combo |
|
| Oxygen, Combo, Sham, MAD | Experimental | Order of interventions: Oxygen, Combo, Sham, MAD |
|
| Oxygen, MAD, Sham, Combo | Experimental | Order of interventions: Oxygen, MAD, Sham, Combo |
|
| Oxygen, Sham, Combo, MAD | Experimental | Order of interventions: Oxygen, Sham, Combo, MAD |
|
| Oxygen, Sham, MAD, Combo | Experimental | Order of interventions: Oxygen, Sham, MAD, Combo |
|
| Sham, Combo, MAD, Oxygen | Experimental | Order of interventions: Sham, Combo, MAD, Oxygen |
|
| Sham, MAD, Combo, Oxygen | Experimental | Order of interventions: Sham, MAD, Combo, Oxygen |
|
| Sham, MAD, Oxygen, Combo | Experimental | Order of interventions: Sham, MAD, Oxygen, Combo |
|
| Sham, Oxygen, Combo, MAD | Experimental | Order of interventions: Sham, Oxygen, Combo, MAD |
|
| Sham, Oxygen, MAD, Combo | Experimental | Order of interventions: Sham, Oxygen, MAD, Combo |
|
|
|
| Oxygen | Drug | Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability. |
|
|
| Oral appliance plus oxygen | Other | Both treatments will be administered simultaneously. |
|
|
| No treatment | Other | Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula. |
|
|
Primary test is difference between combination therapy and oral appliance
| Single night |
| Morning minus evening systolic blood pressure | Primary test is difference between combination therapy and oral appliance | Single night |
| Morning minus evening diastolic blood pressure | Primary test is difference between combination therapy and oral appliance | Single night |
| Notting Hill |
| Victoria |
| 3168 |
| Australia |
| D020920 |
| Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D018011 |
| Chalcogens |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D005740 | Gases |
| D013812 | Therapeutics |