Estimating Apnea Phenotypes From Polysomnography: Oxygen (PSGtraits-O2)

Estimating Apnea Phenotypes From Routine Polysomnography: Application to Oxygen Therapy

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.

Study Overview

• Status: Completed
• Conditions: Sleep Apnea
• Intervention / Treatment: Drug: Inspired oxygen (40%); Other: Sham

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Inspired Oxygen First; 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%); Supplemental oxygen at 40% inspired via venturi mask (15 L/min). Equivalent to 5 L/min via nasal cannula.; Other Names: Supplemental oxygen; Other: Sham; Medical air with 21% oxygen via venturi mask (15 L/min).; Other Names: Medical air
Sham Comparator: Sham First; 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%); Supplemental oxygen at 40% inspired via venturi mask (15 L/min). Equivalent to 5 L/min via nasal cannula.; Other Names: Supplemental oxygen; Other: Sham; Medical air with 21% oxygen via venturi mask (15 L/min).; Other Names: Medical air

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); American Heart Association

Publications and helpful links

General Publications

• Sands SA, Edwards BA, Terrill PI, Butler JP, Owens RL, Taranto-Montemurro L, Azarbarzin A, Marques M, Hess LB, Smales ET, de Melo CM, White DP, Malhotra A, Wellman A. Identifying obstructive sleep apnoea patients responsive to supplemental oxygen therapy. Eur Respir J. 2018 Sep 27;52(3):1800674. doi: 10.1183/13993003.00674-2018. Print 2018 Sep.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: December 12, 2012
• First Submitted That Met QC Criteria: December 14, 2012
• First Posted (Estimate): December 18, 2012

Study Record Updates

• Last Update Posted (Actual): March 20, 2018
• Last Update Submitted That Met QC Criteria: March 19, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Apnea
• Other Study ID Numbers: 2005P001296-O2PSG; R01HL090897 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No