Trial Outcomes & Findings for Combination Therapy to Treat Sleep Apnea (NCT NCT01633827)

NCT ID: NCT01633827

Last Updated: 2017-03-03

Results Overview

Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual. In this table the investigators report the minimum ventilation that can be tolerated before an arousal from sleep (Varousal). It is calculated by slowly reducing the CPAP level from optimum to the minimum tolerable pressure. This trait is symbolized as Varousal (L/min)

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

22 participants

Primary outcome timeframe

Subjects will be assessed on day 1 (visit 1) and up to 1 month (visit 2)

Results posted on

2017-03-03

Participant Flow

Patients with a previous diagnosis of OSA (defined as an apnoea/hypopnoea index \[AHI\] \>10/hr) were recruited from the sleep clinic and Brigham and Women's Hospital and the general community (Boston, MA). The first patient was recruited in September 2012 and the last patient enrolled in May 2014.

Participant milestones

Participant milestones
Measure
Placebo and Air First, Then Eszopiclone and Oxygen
Subjects will receive both a sugar pill and room air during two overnight sleep studies first and subsequently eszopiclone 3 mg with oxygen (FiO2 0.4) after a washout period of 1 week.
Eszopiclone and Oxygen First, Then Placebo and Air
Subjects will receive both eszopiclone and medical grade oxygen (FIO2 0.4) during two overnight sleep studies, after a washout period of 1 week they will receive placebo and air during two overnight sleep studies
First Intervention
STARTED
11
11
First Intervention
COMPLETED
11
11
First Intervention
NOT COMPLETED
0
0
Washout Period
STARTED
11
11
Washout Period
COMPLETED
11
11
Washout Period
NOT COMPLETED
0
0
Second Intervention
STARTED
11
11
Second Intervention
COMPLETED
11
11
Second Intervention
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Combination Therapy to Treat Sleep Apnea

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Study Group
n=20 Participants
This study was a randomized cross-over design so each particiapnt enrolled underweent both placebo and treatment conditions. During the placebo arm, one participant did not have OSA and another exhibited predominantly central sleep apnea; both were excluded from the analysis. Subject demographics for the 20 remaining unselected patients are shown below.
Age, Continuous
50.9 years
STANDARD_DEVIATION 11.8 • n=5 Participants
Gender
Female
8 Participants
n=5 Participants
Gender
Male
12 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
20 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
1 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
7 Participants
n=5 Participants
Race (NIH/OMB)
White
12 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Region of Enrollment
United States
20 participants
n=5 Participants

PRIMARY outcome

Timeframe: Subjects will be assessed on day 1 (visit 1) and up to 1 month (visit 2)

Population: During the placebo arm, one participant did not have OSA and another exhibited predominantly central sleep apnea; both were excluded from the analysis. Subject results for the 20 remaining patients are reported here per intervention.

Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual. In this table the investigators report the minimum ventilation that can be tolerated before an arousal from sleep (Varousal). It is calculated by slowly reducing the CPAP level from optimum to the minimum tolerable pressure. This trait is symbolized as Varousal (L/min)

Outcome measures

Outcome measures
Measure
Placebo Data
n=20 Participants
These result reports the minimum ventilation that can be tolerated before an arousal from sleep under placebo and room air administration
Treatment Data
n=20 Participants
These result reports the minimum ventilation that can be tolerated before an arousal from sleep under the conditions of oxygen and a sedative.
Model Prediction of Absence/Presence of OSA: Ventilation That Causes an Arousal From Sleep (Varousal)
5.7 L/min
Standard Error 0.3
5.2 L/min
Standard Error 0.3

PRIMARY outcome

Timeframe: Subjects will be assessed on day 1 (visit 1) and up to 1 month (visit 2)

Population: During the placebo arm, one participant did not have OSA and another exhibited predominantly central sleep apnea; both were excluded from the analysis. Subject results for the 20 remaining patients are reported here per intervention.

Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual and predicts OSA presence/absence. In this table the investigators report the ventilatory control sensitivity value (Loop Gain). It is calculated dividing the increase in ventilatory drive by the steady state reduction in ventilation. The increase in ventilatory drive is measured as the ventilatory overshoot following a switch to optimal CPAP from the minimum tolerable CPAP. This trait is symbolized as steady state loop gain (LG, adimensional)

Outcome measures

Outcome measures
Measure
Placebo Data
n=20 Participants
These result reports the minimum ventilation that can be tolerated before an arousal from sleep under placebo and room air administration
Treatment Data
n=20 Participants
These result reports the minimum ventilation that can be tolerated before an arousal from sleep under the conditions of oxygen and a sedative.
Model Prediction of Absence/Presence of OSA: Ventilatory Control Sensitivity (Loop Gain)
3.3 ratio, adimensional
Standard Error 0.5
2.20 ratio, adimensional
Standard Error 0.25

PRIMARY outcome

Timeframe: Subjects will be assessed on day 1 (visit 1) and up to 1 month (visit 2)

Population: During the placebo arm, one participant did not have OSA and another exhibited predominantly central sleep apnea; both were excluded from the analysis. Subject results for the 20 remaining patients are reported here per intervention.

Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual and predicts OSA presence/absence. The passive collapsibility of the upper airway is quantified as the ventilation on no CPAP (atmospheric pressure) at the eupneic level of ventilatory drive when upper airway dilator muscles are relatively passive. This trait is symbolized as Vpassive (L/min)

Outcome measures

Outcome measures
Measure
Placebo Data
n=20 Participants
These result reports the minimum ventilation that can be tolerated before an arousal from sleep under placebo and room air administration
Treatment Data
n=20 Participants
These result reports the minimum ventilation that can be tolerated before an arousal from sleep under the conditions of oxygen and a sedative.
Model Prediction of Absence/Presence of OSA: Passive Collapsibility
1.40 L/min
Standard Error 0.5
1.20 L/min
Standard Error 0.41

PRIMARY outcome

Timeframe: Subjects will be assessed on day 1 (visit 1) and up to 1 month (visit 2)

Population: During the placebo arm, one participant did not have OSA and another exhibited predominantly central sleep apnea; both were excluded from the analysis. Subject results for the 20 remaining patients are reported here per intervention.

Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual and predicts OSA presence/absence. Active collapsibility is the ventilation on no CPAP when upper airway muscle are maximally activated. It is calculated by slowing reducing CPAP from the optimal to the minimum tolerable level and rapidly dropping the CPAP to 0 for a few breaths. This trait is symbolized as Vactive (L/min)

Outcome measures

Outcome measures
Measure
Placebo Data
n=20 Participants
These result reports the minimum ventilation that can be tolerated before an arousal from sleep under placebo and room air administration
Treatment Data
n=20 Participants
These result reports the minimum ventilation that can be tolerated before an arousal from sleep under the conditions of oxygen and a sedative.
Model Prediction of Absence/Presence of OSA: Active Collapsibility (Vactive)
4.4 L/min
Standard Error 0.5
4 L/min
Standard Error 0.45

SECONDARY outcome

Timeframe: Subjects will be assessed on day 1 (visit 1) and up to 1 month (visit 2)

Population: During the placebo arm, one participant did not have OSA and another exhibited predominantly central sleep apnea; both were excluded from the analysis. Subject results for the 20 remaining patients are reported here per intervention.

The Apnea-Hypopnea Index (AHI) is an index of sleep apnea severity that encompasses the frequency of apneas (cessations in breathing) and hypopneas (reductions in airflow).

Outcome measures

Outcome measures
Measure
Placebo Data
n=20 Participants
These result reports the minimum ventilation that can be tolerated before an arousal from sleep under placebo and room air administration
Treatment Data
n=20 Participants
These result reports the minimum ventilation that can be tolerated before an arousal from sleep under the conditions of oxygen and a sedative.
Apnea-Hypopnea Index
51.9 events/hr
Standard Error 6.2
29.5 events/hr
Standard Error 5.3

Adverse Events

Study Group

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

David Andrew Wellman

Brigham and Women's Hospital

Phone: 617-732-8483

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place