The Impact of Arousal Threshold in Obstructive Sleep Apnea

NCT ID: NCT02264353

Last Updated: 2019-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2015-05-31

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.

Conditions

Obstructive Sleep Apnea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Donepezil

Sleep data with Donepezil given

Group Type: EXPERIMENTAL

Donepezil

Intervention Type: DRUG

Donepezil 10mg before sleep

Placebo

Sleep data with Placebo given

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

One piece of placebo before sleep

Interventions

Donepezil

Donepezil 10mg before sleep

Intervention Type: DRUG

placebo

One piece of placebo before sleep

Intervention Type: DRUG

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Robert L. Owens

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert Owens, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

University of California, San Diego

San Diego, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 30794310 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27442715 (View on PubMed)

Other Identifiers

UCSD141272

Identifier Type: -

Identifier Source: org_study_id