Obstructive Sleep ApneaPhase 4NCT02264353
The Impact of Arousal Threshold in Obstructive Sleep Apnea
A Phase 4 study testing Donepezil in people with Obstructive Sleep Apnea, run by University of California, San Diego at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Obstructive Sleep Apnea
- What is being tested?
- Donepezil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to May 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ages 18-70 years
- sleep study (with apnea hypopnea index>5)
- Diagnosis of obstructive sleep apnea
Who cannot join
- 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
Show all 13Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego
San Diego, California, 92093
About this study
Official title: The Impact of Arousal Threshold in Obstructive Sleep Apnea: Donepezil's Effects on the Arousal Threshold and on the Apnea Hypopnea Index
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.
Read the 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.
- Conditions
- Obstructive Sleep Apnea
- Being tested
- Donepezil, placebo
- Keywords
- Obstructive, Sleep Apnea, Arousal threshold, Donepezil
- Medical subject headings
- Sleep Apnea, Obstructive, Sleep Apnea Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DonepezilDrug
Donepezil 10mg before sleep
placeboDrug
One piece of placebo before sleep
| Study group | Role | What they receive |
|---|---|---|
| Donepezil | Experimental | Sleep data with Donepezil given Receives: Drug: Donepezil |
| Placebo | Placebo comparator | Sleep data with Placebo given Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 14 days (during overnight sleep study after donepezil or placebo is given)
Secondary outcomes (1)
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.
Measured: 14 days (during overnight sleep study after donepezil or placebo is given)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2014 (estimated)
- Study startSep 2014
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Obstructive Sleep ApneaStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert L. Owens, University of California, San Diego
- Investigators
- Robert Owens, M.D., Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02264353
- Sponsor's protocol ID
- UCSD141272
- Status last verified
- Aug 2019
- First submitted
- 17 Sep 2014
- Last updated
- 8 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 30794310Li 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.
PubMed 27442715
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Arousal Threshold in Obstructive Sleep Apnea: Donepezil's Effects on the Arousal Threshold and on the Apnea Hypopnea Index
- ClinicalTrials.gov ID
- NCT02264353
- Acronym / sponsor ID
- UCSD141272
- Conditions
- Obstructive Sleep Apnea
- Keywords
- Obstructive, Sleep Apnea, Arousal threshold, Donepezil
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 15 Oct 2014 (estimated)
- Results
- Posted 8 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Donepezil | Experimental | Drug: DonepezilSleep data with Donepezil given |
| Placebo | Placebo comparator | Drug: placeboSleep data with Placebo given |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Ages 18-70 years
- sleep study (with apnea hypopnea index>5)
- Diagnosis of obstructive sleep apnea
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DonepezilDonepezil 10mg before sleep | Drug | Donepezil |
| placeboOne piece of placebo before sleep | Drug | Placebo |
Primary outcome
Apnea Hypopnea Index (AHI)
Time frame: 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
1 secondary outcome
Respiratory Arousal Threshold
Time frame: 14 days (during overnight sleep study after donepezil or placebo is given)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30794310Li 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.
- Derived from this study: PubMed 27442715Li 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Owens, M.D. principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Donepezil in people with Obstructive Sleep Apnea, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Apnea Hypopnea Index (AHI) (time frame: 14 days (during overnight sleep study after donepezil or placebo is given)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02264353, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2019.