A Phase 4 interventional study of Donepezil and placebo in Obstructive Sleep Apnea, sponsored by University of California, San Diego. Completed at 1 site in United States. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2019-08-08.
Sponsored by University of California, San Diego · Phase 4, Interventional, and Treatment
The investigators hypothesis is that obstructive sleep apnea (OSA) patients with a low arousal threshold may wake up too early during a respiratory event, before upper airway muscles can be activated to achieve stable ventilation. Thus, strategies to manipulate the respiratory arousal threshold could potentially improve the quality of sleep and sleep disordered breathing. Agents that raise arousal threshold are therefore likely to benefit some patients with OSA. The overall goal of this project is to determine the importance of the arousal threshold in OSA, determine which patients might benefit from a raised arousal threshold, and test this hypothesis by using pharmacological manipulation of the arousal threshold to achieve this goal.
This study is a pilot study. The investigators will test whether donepezil has important effects on the arousal threshold and on the apnea hypopnea index.
Donepezil is a cholinesterase inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of symptoms of Alzheimer's disease.
Eligible participants will undergo overnight polysomonography as described below and will receive either donepezil (10 mg immediately prior to sleep) or placebo (in random order) followed roughly 14 days later with placebo or donepezil. This aim will allow us to test the impact of donepezil on the apnea hypopnea index. The study plans to enroll approximately 30 subjects.
The change in apnea hypopnea index as well as arousal thresholds/upper airway mechanics will be compared in the donepezil groups with the placebo group.
1,422 studies on the registry are indexed under Apnea; 160 are open to participants now.
This study's enrollment of 44 is below the median of 51 across 966 interventional studies indexed under Apnea.
Browse Apnea studies →University of California, San Diego is the lead sponsor of 958 studies on the registry; 191 are open to participants now.
Of its 110 completed or terminated interventional studies of FDA-regulated products, 70 (64%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Sleep data with Donepezil given
Drug: Donepezil
Sleep data with Placebo given
Drug: placebo
Donepezil 10mg before sleep
One piece of placebo before sleep
Apnea Hypopnea Index (AHI)
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
Time frame: 14 days (during overnight sleep study after donepezil or placebo is given)
Respiratory Arousal Threshold
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.
Time frame: 14 days (during overnight sleep study after donepezil or placebo is given)
Loop Gain
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
Time frame: 14 days (during overnight sleep study after donepezil or placebo is given)
| Milestone | Donepezil Then Placebo | Placebo Then Donepezil |
|---|---|---|
| Started | 20 | 24 |
| Completed | 17 | 24 |
| Not completed | 3 | 0 |
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
| events/hour | Donepezil | Placebo |
|---|---|---|
| Apnea Hypopnea Index (AHI) | 50.0 ± 23.4 | 51.8 ± 27.4 |
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.
| cm H20 | Donepezil | Placebo |
|---|---|---|
| Respiratory Arousal Threshold | -18.0 (-27.0 to -11.8) | -18.9 (-27.5 to -12.3) |
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
| Unitless | Donepezil | Placebo |
|---|---|---|
| Loop Gain | 0.55 ± 0.15 | 0.58 ± 0.16 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Donepezil | 0/41 (0%) | 0/41 (0%) | 0/41 (0%) |
| Placebo | 0/41 (0%) | 0/41 (0%) | 2/41 (4.9%) |
| Event | Donepezil | Placebo |
|---|---|---|
| Heart BurnInvestigations | 0/41 | 1/41 |
| Difficulty Falling AsleepInvestigations | 0/41 | 1/41 |
| Age, Categorical(Participants) | All Study Participants |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 40 |
| >=65 years | 1 |
| Age, Continuous(years) | All Study Participants |
|---|---|
| Mean | 51.6 ± 11.1 |
| Sex: Female, Male(Participants) | All Study Participants |
|---|---|
| Female | 14 |
| Male | 27 |
| Ethnicity (NIH/OMB)(Participants) | All Study Participants |
|---|---|
| Hispanic or Latino | 7 |
| Not Hispanic or Latino | 34 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | All Study Participants |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 5 |
| Native Hawaiian or Other Pacific Islander | 1 |
| Black or African American | 0 |
| White | 33 |
| More than one race | 2 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | All Study Participants |
|---|---|
| United States | 41 |
| Apnea Hypopnea Index (AHI)>5 events/hr; lowest Oxygen Saturation (SaO2)>70%(Participants) | All Study Participants |
|---|---|
| Count of participants | 41 |
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University of California, San Diego