Clinical trial NCT01751971: Estimating Apnea Phenotypes From Polysomnography: Oxygen
Official title: Estimating Apnea Phenotypes From Routine Polysomnography: Application to Oxygen Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sleep Apnea
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: American Heart Association
First posted: 2012-12-18
Enrollment: 47
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Apnea-hypopnea Index
timeFrame: 1 night
Secondary outcomes:
measure: Frequency of EEG Arousals (Events Per Hour)
timeFrame: 1 night
measure: Overnight Change in Systolic Blood Pressure
timeFrame: 1 night
measure: Overnight Change in Diastolic Blood Pressure
timeFrame: 1 night
measure: Subjective Sleep Quality (Oxygen vs Sham)
timeFrame: 1 night
measure: Subjective Sleepiness/Alertness (Stanford Sleepiness Scale)
timeFrame: 1 night
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: SCOTT A Sands, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.