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NCT Number: NCT02264353

The Impact of Arousal Threshold in Obstructive Sleep Apnea

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.

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Key information

Conditions

Obstructive Sleep Apnea Apnea Dyssomnias Nervous System Diseases Respiration Disorders Respiratory Tract Diseases Sleep Apnea Syndromes Sleep Apnea, Obstructive Sleep Disorders, Intrinsic Sleep Wake Disorders

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University of California, San Diego

San Diego, California, 92093, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Donepezil

Drug

Donepezil 10mg before sleep

Placebo

Drug

One piece of placebo before sleep

Primary outcomes

  1. 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

Secondary outcomes

  1. 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.

Other outcomes

  1. 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

Sponsors and collaborators

Lead sponsor

University of California, San Diego

Other

Registry information

Official study title

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

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Oct 15, 2014
Registry last updated
Aug 8, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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