The Impact of Arousal Threshold in Obstructive Sleep Apnea
Primary Purpose
Obstructive Sleep Apnea
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Donepezil
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Obstructive Sleep Apnea focused on measuring Obstructive, Sleep Apnea, Arousal threshold, Donepezil
Eligibility Criteria
Inclusion Criteria:
- Ages 18-70 years
- sleep study (with apnea hypopnea index>5)
- Diagnosis of obstructive sleep apnea
Exclusion Criteria:
- Any known unstable cardiac (apart from treated hypertension), pulmonary (including asthma), renal, neurologic (including epilepsy), neuromuscular, or hepatic disease.
- Susceptible to stomach ulcers.
- Pregnant women or Nursing mothers
- Using positive airway pressure (PAP) therapy over one week or longer
- Body weight <55kg
- History of hypersensitivity to Afrin, Lidocaine and/or Donepezil
- History of bleeding diathesis and/or gastrointestinal bleeding.
- Use of any medications that may affect sleep or breathing.
- A psychiatric disorder, other than mild depression; e.g. schizophrenia, bipolar disorder, major depression, panic or anxiety disorders.
- Substantial cigarette (>5/day), alcohol (>3oz/day) or use of illicit drugs.
- More than 10 cups of beverages with caffeine (coffee, tea, soda/pop) per day.
- Deprived from sleep in the recent one week
- Desaturations to below 70% lasting greater than 10 seconds in duration per event in the sleep study (without Oxygen).
Sites / Locations
- University of California, San Diego
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Donepezil
Placebo
Arm Description
Sleep data with Donepezil given
Sleep data with Placebo given
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT02264353
First Posted
September 17, 2014
Last Updated
August 6, 2019
Sponsor
University of California, San Diego
1. Study Identification
Unique Protocol Identification Number
NCT02264353
Brief Title
The Impact of Arousal Threshold in Obstructive Sleep Apnea
Official Title
The Impact of Arousal Threshold in Obstructive Sleep Apnea: Donepezil's Effects on the Arousal Threshold and on the Apnea Hypopnea Index
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
September 2014 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
May 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obstructive Sleep Apnea
Keywords
Obstructive, Sleep Apnea, Arousal threshold, Donepezil
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Donepezil
Arm Type
Experimental
Arm Description
Sleep data with Donepezil given
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Sleep data with Placebo given
Intervention Type
Drug
Intervention Name(s)
Donepezil
Intervention Description
Donepezil 10mg before sleep
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
One piece of placebo before sleep
Primary Outcome Measure Information:
Title
Apnea Hypopnea Index (AHI)
Description
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)
Secondary Outcome Measure Information:
Title
Respiratory Arousal Threshold
Description
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)
Other Pre-specified Outcome Measures:
Title
Loop Gain
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Ages 18-70 years
sleep study (with apnea hypopnea index>5)
Diagnosis of obstructive sleep apnea
Exclusion Criteria:
Any known unstable cardiac (apart from treated hypertension), pulmonary (including asthma), renal, neurologic (including epilepsy), neuromuscular, or hepatic disease.
Susceptible to stomach ulcers.
Pregnant women or Nursing mothers
Using positive airway pressure (PAP) therapy over one week or longer
Body weight <55kg
History of hypersensitivity to Afrin, Lidocaine and/or Donepezil
History of bleeding diathesis and/or gastrointestinal bleeding.
Use of any medications that may affect sleep or breathing.
A psychiatric disorder, other than mild depression; e.g. schizophrenia, bipolar disorder, major depression, panic or anxiety disorders.
Substantial cigarette (>5/day), alcohol (>3oz/day) or use of illicit drugs.
More than 10 cups of beverages with caffeine (coffee, tea, soda/pop) per day.
Deprived from sleep in the recent one week
Desaturations to below 70% lasting greater than 10 seconds in duration per event in the sleep study (without Oxygen).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Owens, M.D.
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
30794310
Citation
Li Y, Orr J, Jen R, Sands SA, DeYoung P, Smales E, Edwards B, Owens RL, Malhotra A. Is there a threshold that triggers cortical arousals in obstructive sleep apnea. Sleep. 2019 Jun 11;42(6):zsz047. doi: 10.1093/sleep/zsz047.
Results Reference
derived
PubMed Identifier
27442715
Citation
Li Y, Owens RL, Sands S, Orr J, Moraes W, DeYoung P, Smales E, Jen R, Malhotra A. The Effect of Donepezil on Arousal Threshold and Apnea-Hypopnea Index. A Randomized, Double-Blind, Cross-Over Study. Ann Am Thorac Soc. 2016 Nov;13(11):2012-2018. doi: 10.1513/AnnalsATS.201605-384OC.
Results Reference
derived
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The Impact of Arousal Threshold in Obstructive Sleep Apnea
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