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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

About this trial

This is an interventional treatment trial for Obstructive Sleep Apnea focused on measuring Obstructive, Sleep Apnea, Arousal threshold, Donepezil

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

Time Frame

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

Secondary Outcome Measure Information:

Title

Respiratory Arousal Threshold

Description

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

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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