Trial Outcomes & Findings for The Impact of Arousal Threshold in Obstructive Sleep Apnea (NCT NCT02264353)

NCT ID: NCT02264353

Last Updated: 2019-08-08

Results Overview

The Apnea-Hypopnea Index or Apnoea-Hypopnoea Index (AHI) is an index used to indicate the severity of sleep apnea. It is represented by the number of apnea and hypopnea events per hour of sleep. The apneas (pauses in breathing) must last for at least 10 seconds and be associated with a decrease in blood oxygenation. A higher AHI value indicates more severe sleep apnea

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

44 participants

Primary outcome timeframe

14 days (during overnight sleep study after donepezil or placebo is given)

Results posted on

2019-08-08

Participant Flow

Participant milestones

Participant milestones
Measure
Donepezil Then Placebo
Sleep data with Donepezil given during Visit 1 followed by a 14 day washout period followed by Sleep data with Placebo given during Visit 2 Donepezil: Donepezil 10mg before sleep
Placebo Then Donepezil
Sleep data with Placebo given during Visit 1 followed by a 14 day washout period followed by Sleep data with Donepezil given during Visit 2 placebo: One piece of placebo before sleep
Overall Study
STARTED
20
24
Overall Study
COMPLETED
17
24
Overall Study
NOT COMPLETED
3
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The Impact of Arousal Threshold in Obstructive Sleep Apnea

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
All Study Participants
n=41 Participants
Participants who were randomized to receive either Donepezil 10mg tablet or Placebo tablet (matching Donepezil 10mg) before sleep
Age, Categorical
<=18 years
0 Participants
n=99 Participants
Age, Categorical
Between 18 and 65 years
40 Participants
n=99 Participants
Age, Categorical
>=65 years
1 Participants
n=99 Participants
Age, Continuous
51.6 years
STANDARD_DEVIATION 11.1 • n=99 Participants
Sex: Female, Male
Female
14 Participants
n=99 Participants
Sex: Female, Male
Male
27 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
7 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
34 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=99 Participants
Race (NIH/OMB)
Asian
5 Participants
n=99 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
1 Participants
n=99 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=99 Participants
Race (NIH/OMB)
White
33 Participants
n=99 Participants
Race (NIH/OMB)
More than one race
2 Participants
n=99 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
Region of Enrollment
United States
41 participants
n=99 Participants
Apnea Hypopnea Index (AHI)>5 events/hr; lowest Oxygen Saturation (SaO2)>70%
41 Participants
n=99 Participants

PRIMARY outcome

Timeframe: 14 days (during overnight sleep study after donepezil or placebo is given)

The Apnea-Hypopnea Index or Apnoea-Hypopnoea Index (AHI) is an index used to indicate the severity of sleep apnea. It is represented by the number of apnea and hypopnea events per hour of sleep. The apneas (pauses in breathing) must last for at least 10 seconds and be associated with a decrease in blood oxygenation. A higher AHI value indicates more severe sleep apnea

Outcome measures

Outcome measures
Measure
Donepezil
n=41 Participants
Sleep data with Donepezil given Donepezil: Donepezil 10mg before sleep
Placebo
n=41 Participants
Sleep data with Placebo given placebo: One piece of placebo before sleep
Apnea Hypopnea Index (AHI)
50.0 events/hour
Standard Deviation 23.4
51.8 events/hour
Standard Deviation 27.4

SECONDARY outcome

Timeframe: 14 days (during overnight sleep study after donepezil or placebo is given)

Arousal Threshold was measured as the average nadir epiglottic airway pressure immediately before electroencephalogram (EEG) arousal. It was measured with an epiglottic pressure catheter. The epiglottic catheter/balloon is linked in a pressure catheter inserted through the de-congested, anesthetized nostril and the tip of the catheter located at hypopharyngeal area.

Outcome measures

Outcome measures
Measure
Donepezil
n=21 Participants
Sleep data with Donepezil given Donepezil: Donepezil 10mg before sleep
Placebo
n=21 Participants
Sleep data with Placebo given placebo: One piece of placebo before sleep
Respiratory Arousal Threshold
-18.0 cm H20
Interval -27.0 to -11.8
-18.9 cm H20
Interval -27.5 to -12.3

OTHER_PRE_SPECIFIED outcome

Timeframe: 14 days (during overnight sleep study after donepezil or placebo is given)

The sensitivity of the ventilatory control system (loop gain) was quantified by fitting a simplified mathematical model to the spontaneous ventilatory pattern of obstructive sleep apnea (OSA). The sensitivity of the ventilatory control system (loop gain) was quantified by fitting a simplified mathematical model to the spontaneous ventilatory pattern of OSA 21. Loop gain is reflected in the size of the ventilatory overshoot following a ventilatory perturbation (hypopnea/apnea), where loop gain = response/disturbance. Ventilatory fluctuations are estimated using the square-root transformed nasal pressure waveform. Loop gain was reported as the ventilatory response to a 1 cycle/min disturbance (LG1); a value of LGn\>1 yields periodic central apnea. Calculations were performed using MATLAB

Outcome measures

Outcome measures
Measure
Donepezil
n=41 Participants
Sleep data with Donepezil given Donepezil: Donepezil 10mg before sleep
Placebo
n=41 Participants
Sleep data with Placebo given placebo: One piece of placebo before sleep
Loop Gain
0.55 Unitless
Standard Deviation 0.15
0.58 Unitless
Standard Deviation 0.16

Adverse Events

Donepezil

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

Placebo

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Donepezil
n=41 participants at risk
Sleep data with Donepezil given Donepezil: Donepezil 10mg before sleep
Placebo
n=41 participants at risk
Sleep data with Placebo given placebo: One piece of placebo before sleep
Investigations
Heart Burn
0.00%
0/41
2.4%
1/41 • Number of events 1
Investigations
Difficulty Falling Asleep
0.00%
0/41
2.4%
1/41 • Number of events 1

Additional Information

Atul Malhotra, MD

University of California, San Diego

Phone: (858) 657-6159

Results disclosure agreements

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