The Impact of Arousal Threshold in Obstructive Sleep Apnea

Obstructive Sleep Apnea Clinical Trial

Official title:

The Impact of Arousal Threshold in Obstructive Sleep Apnea: Donepezil's Effects on the Arousal Threshold and on the Apnea Hypopnea Index

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02264353
• Other study ID #: UCSD141272
• Status: Completed
• Phase: Phase 4
• Start date: September 2014
• Est. completion date: May 2015

Study information

• Verified date: August 2019
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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).

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• Donepezil
Donepezil 10mg before sleep
• placebo
One piece of placebo before sleep

Locations

Country	Name	City	State
United States	University of California, San Diego	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Loop Gain	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)
Primary	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	14 days (during overnight sleep study after donepezil or placebo is given)
Secondary	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.	14 days (during overnight sleep study after donepezil or placebo is given)