Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| R01HL090897 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| American Heart Association | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Inspired Oxygen First | Active Comparator | 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). |
|
| Sham First | Sham Comparator | 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Inspired oxygen (40%) | Drug | Supplemental oxygen at 40% inspired via venturi mask (15 L/min). Equivalent to 5 L/min via nasal cannula. |
|
| 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 |
| 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| SCOTT A Sands, PhD | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30139771 | Derived | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Oxygen First | Participants participate in inspired oxygen arm (40% oxygen) first, then the air night (21% oxygen) second Inspired oxygen (40%): Supplemental oxygen at approximately 40% e.g. via Pink venturi mask |
| FG001 | Air First | Participants participate in the air night (sham) first, then the oxygen night second. Sham: Medical air with 21% oxygen e.g. via Pink venturi mask |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Oxygen First | Participants participate in inspired oxygen arm (40% oxygen) first, then the air night (21% oxygen) second Inspired oxygen (40%): Supplemental oxygen at approximately 40% e.g. via Pink venturi mask |
| BG001 | Air First |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Patients with AHI>20 | Posted | Mean | Standard Error | events/hour | 1 night |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Inspired Oxygen | Inspired Oxygen 40% | 0 |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Scott Sands, PhD | Brigham and Women's Hospital | 6172780911 | sasands@bwh.harvard.edu |
Not provided
| ID | Term |
|---|---|
| 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 |
|---|---|
| C005703 | salicylhydroxamic acid |
| D000388 | Air |
| ID | Term |
|---|---|
| D001272 | Atmosphere |
| D004777 | Environment |
| D055669 | Ecological and Environmental Phenomena |
| D001686 | Biological Phenomena |
Not provided
Not provided
Not provided
Not provided
Not provided
Participants were not informed whether they were breathing supplemental inspired oxygen or sham (air) on the study night. Technicians and investigators performing the study were not masked in order to carefully ensure delivery of treatment.
|
| Sham | Other | Medical air with 21% oxygen via venturi mask (15 L/min). |
|
|
| 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 |
Participants participate in the air night (sham) first, then the oxygen night second.
Sham: Medical air with 21% oxygen e.g. via Pink venturi mask
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Inspired oxygen (40%) for 1 night via venturi mask. |
| OG001 | Sham | Sham: Medical air with 21% oxygen via venturi mask |
|
|
|
| Secondary | 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. | Patients with AHI>20 | Posted | Mean | Standard Error | events/hr | 1 night |
|
|
|
| Secondary | 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). | Patients with AHI>20 | Posted | Mean | Standard Error | mmHg | 1 night |
|
|
|
| Secondary | 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). | Patients with AHI>20 | Posted | Mean | Standard Error | mmHg | 1 night |
|
|
|
| Secondary | 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. | Patients with AHI>20. One patient, whose treatment and sham nights were separated by an extended duration (due to scheduling), did not provide data for this outcome measure. | Posted | Mean | Standard Deviation | units on a scale | 1 night |
|
|
|
| Secondary | 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). | Patients with AHI>20 | Posted | Mean | Standard Error | Scores on a scale | 1 night |
|
|
|
| 46 |
| 0 |
| 46 |
| 0 |
| 46 |
| EG001 | Sham | Sham, room air | 0 | 45 | 0 | 45 | 0 | 45 |
Not provided
Not provided
Not provided
| D020920 |
| Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D008685 |
| Meteorological Concepts |
| D004778 | Environment and Public Health |
| Patients with favorable pathophysiology |
|
|
| Patients with unfavorable pathophysiology |
|
|
| Patients with favorable pathophysiology |
|
|
| Patients with unfavorable pathophysiology |
|
|
| Patients with favorable pathophysiology |
|
|
| Patients with unfavorable pathophysiology |
|
|
|
| Patients with unfavorable pathophysiology |
|
|
| Patients with favorable pathophysiology |
|
|
| Patients with unfavorable pathophysiology |
|
|