The Impact of Arousal Threshold in Obstructive Sleep Apnea

August 6, 2019 updated by: Robert L. Owens, University of California, San Diego

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

44

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92093
        • University of California, San Diego

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Donepezil
Sleep data with Donepezil given
Drug: Donepezil
Donepezil 10mg before sleep
Placebo Comparator: Placebo
Sleep data with Placebo given
Drug: placebo
One piece of placebo before sleep

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
14 days (during overnight sleep study after donepezil or placebo is given)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Respiratory Arousal Threshold
Time Frame: 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.
14 days (during overnight sleep study after donepezil or placebo is given)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Loop Gain
Time Frame: 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
14 days (during overnight sleep study after donepezil or placebo is given)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Diego

Investigators

  • Principal Investigator: Robert Owens, M.D., University of California, San Diego

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2014

Primary Completion (Actual)

May 1, 2015

Study Completion (Actual)

May 1, 2015

Study Registration Dates

First Submitted

September 17, 2014

First Submitted That Met QC Criteria

October 8, 2014

First Posted (Estimate)

October 15, 2014

Study Record Updates

Last Update Posted (Actual)

August 8, 2019

Last Update Submitted That Met QC Criteria

August 6, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCSD141272

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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