Estimating Apnea Phenotypes From Polysomnography: Oxygen

Study Overview
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Brief Summary
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This study seeks to employ advanced methods to estimate the individual factors contributing to sleep apnea from standard recordings made during routine clinical sleep studies. This study focuses on breathing control or loop gain as one of the factors contributing to sleep apnea. Increased levels of oxygen in the air is known to make breathing more stable by lowering loop gain. Here, our goal is to use a new method capable of detecting a reduction in loop gain with oxygen. The investigators also aim to test whether a high loop gain measured at baseline/placebo predicts a greater improvement in sleep apnea with oxygen therapy.

Detailed Description
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In a single-blinded randomized crossover study, inspired oxygen/air (40%/21%) is delivered on two separate nights. Loop gain is measured from routine polysomnography using a novel mathematical method. A value of loop gain >1 reflects unstable breathing, and a value less than but approaching 1 denotes a system more prone to oscillate. Loop gain is measured as the changes in ventilatory drive/effort that arises subsequent to changes in ventilation (e.g. due to obstructive apnea). A simple chemoreflex model (gain, time constant, delay) is fit to surrogate ventilation data (derived from airflow) during sleep. The best model is one that best matches the elevated ventilatory drive (measured as ventilation in the absence of airflow obstruction) based on the prior apneic/hypopneic fall in ventilation. Loop gain is calculated from this model. We aim to use loop gain measured on and off oxygen to determine whether a strong response (reduction in apnea severity) can be predicted by a higher loop gain (in the sham arm) using our method. We also assessed whether assessing upper airway anatomy/collapsibility, dilator muscle responsiveness, and the arousal threshold helped to predict responses to treatment.

Official Title
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Estimating Apnea Phenotypes From Routine Polysomnography: Application to Oxygen Therapy

Conditions
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Sleep Apnea

Intervention / Treatment
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* Drug: Inspired oxygen (40%)
* Other: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Apnea/hypopnea index >20 events per hour Age 20-79 years Exclusion Criteria: COPD with desaturation (resting SpO2<96%) Use of respiratory stimulants or depressants Pregnancy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 79 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Inspired Oxygen First<br>Participants breathe air with additional inspired oxygen (40%) for 1 night during an overnight sleep study (15 L/min via venturi mask). 1 week later participants will crossover to Sham (sham comparator). | Drug: Inspired oxygen (40%)<br>* Supplemental oxygen at 40% inspired via venturi mask (15 L/min). Equivalent to 5 L/min via nasal cannula.<br>* Other names: Supplemental oxygen;Other: Sham<br>* Medical air with 21% oxygen via venturi mask (15 L/min).<br>* Other names: Medical air;|
| Sham Comparator: Sham First<br>Participants breathe air without additional inspired oxygen for 1 night during sleep (15 L/min via Venturi mask). 1 week later participants will crossover to Inspire Oxygen (active intervention). | Drug: Inspired oxygen (40%)<br>* Supplemental oxygen at 40% inspired via venturi mask (15 L/min). Equivalent to 5 L/min via nasal cannula.<br>* Other names: Supplemental oxygen;Other: Sham<br>* Medical air with 21% oxygen via venturi mask (15 L/min).<br>* Other names: Medical air;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apnea-hypopnea Index | Apnea-hypopnea index (AHI) will be compared between oxygen and sham nights. Hypopneas are based on 30% reduction in airflow (no desaturation or arousal criteria). AHI data are exclusive to non-REM supine sleep. The results presented here are for the AHI at each intervention (per intervention) regardless of the sequence (preferred clinicaltrials.gov format). Please note, however, that the a priori outcome measure was the reduction in AHI with oxygen as a percent of sham values, i.e. (AHI on sham - AHI on oxygen)/(AHI on sham) % (a comparison with greater statistical power), compared between patient subgroups (see Statistical Analysis section). Subgroups were defined a priori as higher (>=0.7) versus lower loop gain (<0.7), but tests were also performed in subgroups defined by favorable versus unfavorable pathophysiology. | 1 night | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of EEG Arousals (Events Per Hour) | Frequency of scored EEG arousals per hour of non-REM sleep. Note: Our objective was to describe changes in secondary outcomes within phenotypic subgroups. Overall effects (unselected patients / ignoring phenotypic subgroups) are first presented below, followed by effects in favorable vs. unfavorable subgroups. | 1 night | 
| Overnight Change in Systolic Blood Pressure | The change in systolic blood pressure overnight. Two supine oscillometric measurements of blood pressure are made: just prior to lights out (evening), and after lights on (morning). | 1 night | 
| Overnight Change in Diastolic Blood Pressure | The change in diastolic blood pressure overnight. Two supine oscillometric measurements of blood pressure are made: just prior to lights out (evening), and after lights on (morning). | 1 night | 
| Subjective Sleep Quality (Oxygen vs Sham) | Better(+1)/Same(0)/Worse(-1) on oxygen vs sham, i.e. a relative comparison between arms. When subjects had completed the entire study, they were asked to compare subjectively their sleep quality on the first versus second study. | 1 night | 
| Subjective Sleepiness/Alertness (Stanford Sleepiness Scale) | Assessed in the morning after the single night of treatment. Minimum score: 1 (alert), maximum score: 7 (not alert). | 1 night |