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Combined Upper-airway and Breathing Control Therapies for Obstructive Sleep Apnea

Primary Purpose

Obstructive Sleep Apnea

Status

Active

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Oral appliance

Oxygen

Oral appliance plus oxygen

No treatment

About this trial

This is an interventional treatment trial for Obstructive Sleep Apnea focused on measuring Obstructive Sleep Apnea, Ventilatory Control Instability, Complex Sleep Apnea

Eligibility Criteria

21 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Brigham and Women's Hospital
Sleep and Circadian Medicine Laboratory, BASE Facility, Monash University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All patients

Arm Description

Patients will receive all four interventions in randomized order. Note: Data will not be analyzed separately for the 16 cross-over combinations of intervention order: Interventions: Oral appliance | Oral appliance plus oxygen | Oxygen | No treatment

Outcomes

Primary Outcome Measures

Change in apnea hypopnea index (AHI), percent of baseline.

Primary test is difference between combination therapy and oral appliance

Secondary Outcome Measures

Change in frequency of arousals, percent of baseline.

Primary test is difference between combination therapy and oral appliance

Patient reported sleep quality (better/same/worse)

Primary test is difference between combination therapy and oral appliance

Morning minus evening systolic blood pressure

Primary test is difference between combination therapy and oral appliance

Morning minus evening diastolic blood pressure

Primary test is difference between combination therapy and oral appliance

Full Information

NCT ID

NCT03189173

First Posted

June 14, 2017

Last Updated

July 12, 2023

Sponsor

Brigham and Women's Hospital

Collaborators

Monash University, American Heart Association, National Heart, Lung, and Blood Institute (NHLBI), Heart Foundation of Australia

1. Study Identification

Unique Protocol Identification Number

NCT03189173

Brief Title

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

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 6, 2017 (Actual)

Primary Completion Date

December 1, 2023 (Anticipated)

Study Completion Date

December 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Brigham and Women's Hospital

Collaborators

Monash University, American Heart Association, National Heart, Lung, and Blood Institute (NHLBI), Heart Foundation of Australia

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Obstructive Sleep Apnea

Keywords

Obstructive Sleep Apnea, Ventilatory Control Instability, Complex Sleep Apnea

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

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.

Masking

None (Open Label)

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".

Allocation

N/A

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

All patients

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

Oral appliance

Other Intervention Name(s)

Mandibular advancement device

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Oxygen

Other Intervention Name(s)

Supplemental inspired oxygen

Intervention Description

Supplemental oxygen will be delivered at 4 L/min via nasal cannula to improve ventilatory control stability.

Intervention Type

Other

Intervention Name(s)

Oral appliance plus oxygen

Other Intervention Name(s)

Combination therapy

Intervention Description

Both treatments will be administered simultaneously.

Intervention Type

Other

Intervention Name(s)

No treatment

Other Intervention Name(s)

Sham

Intervention Description

Subjects will not wear an oral appliance, and will be administered sham (room air) at 4 L/min via nasal cannula.

Primary Outcome Measure Information:

Title

Change in apnea hypopnea index (AHI), percent of baseline.

Description

Primary test is difference between combination therapy and oral appliance

Time Frame

Single night

Secondary Outcome Measure Information:

Title

Change in frequency of arousals, percent of baseline.

Description

Primary test is difference between combination therapy and oral appliance

Time Frame

Single night

Title

Patient reported sleep quality (better/same/worse)

Description

Primary test is difference between combination therapy and oral appliance

Time Frame

Single night

Title

Morning minus evening systolic blood pressure

Description

Primary test is difference between combination therapy and oral appliance

Time Frame

Single night

Title

Morning minus evening diastolic blood pressure

Description

Primary test is difference between combination therapy and oral appliance

Time Frame

Single night

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

79 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Scott A Sands, PhD

Organizational Affiliation

Brigham and Women's Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Bradley A Edwards, PhD

Organizational Affiliation

Monash University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Brigham and Women's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Sleep and Circadian Medicine Laboratory, BASE Facility, Monash University

City

Notting Hill

State/Province

Victoria

ZIP/Postal Code

3168

Country

Australia

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Fully-deidentified subject data will be shared via an online repository.

Learn more about this trial

Combined Upper-airway and Breathing Control Therapies for Obstructive Sleep Apnea

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