The Impact of Arousal Threshold in Obstructive Sleep Apnea

NCT02264353 | Completed Phase 4 Results

• 1 other identifier: UCSD141272
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Obstructive Sleep Apnea

Keywords

Obstructive; Sleep Apnea; Arousal threshold; Donepezil

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Respiratory Arousal Threshold

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

Other Outcomes (1)

• Loop Gain

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

Study Arms (2)

Donepezil

EXPERIMENTAL

Sleep data with Donepezil given

Drug: Donepezil

Placebo

PLACEBO COMPARATOR

Sleep data with Placebo given

Drug: placebo

Interventions

Donepezil DRUG

Donepezil 10mg before sleep

Donepezil

placebo DRUG

One piece of placebo before sleep

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18-70 years
• sleep study (with apnea hypopnea index\>5)
• Diagnosis of obstructive sleep apnea

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

University of California, San Diego

San Diego, California, 92093, United States

Location

Related Publications (2)

• 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.

  PMID: 30794310 DERIVED

• 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.

  PMID: 27442715 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Sleep Apnea Syndromes

Interventions

Donepezil

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Limitations and Caveats

Underlying mechanism(s) of sleep apnea is likely to vary across individuals such that one might predict that an intervention may only be effective in a subset of OSA patients. We did not measure upper airway gain.

Results Point of Contact

• Title: Atul Malhotra, MD
• Organization: University of California, San Diego

amalhotra@ucsd.edu

(858) 657-6159

Study Officials

• Robert Owens, M.D.

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 17, 2014
• First Posted: October 15, 2014
• Study Start: September 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: August 8, 2019
• Results First Posted: August 8, 2019

Record last verified: 2019-08

Locations

US (1)