The Impact of Arousal Threshold in Obstructive Sleep Apnea

University of California San Diego

Status and phase

Completed

Phase 4

Conditions

Obstructive Sleep Apnea

Treatments

Drug: placebo

Drug: Donepezil

Study type

Interventional

Funder types

Other

Identifiers

NCT02264353

UCSD141272

Details and patient eligibility

About

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.

Full 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.

Enrollment

44 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No 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).