Donepezil, Residual Excessive Daytime Sleepiness, Obstructive Sleep Apnea

Donepezil for Residual Symptoms in CPAP Treated Obstructive Sleepapnea Patients: A Controlled Study

It is a randomized, double-blind, single-center, 30-day study. Patients aged 35-60 years, with apnea and hypopnea index and respiratory disturbance index normalized with CPAP, and Epworth Sleepiness Scale> 11. Patients undergo baseline and CPAP titration polysomnography, liquor and blood collection, Multiple Sleep Latency Test, anxiety and depression and cognitive assessments.

Study Overview

• Status: Unknown
• Conditions: OSA; Sleepiness
• Intervention / Treatment: Drug: donepezil treatment

Detailed Description

Obstructive Sleep Apnea (OSA) is a sleep-disordered breathing characterized by recurrent episodes of total or partial obstruction of the upper airway during sleep, which can lead to cognitive, metabolic and cardiovascular consequences. More recently, OSA has been associated with worsening Alzheimer's disease symptoms. Resolving respiratory events during sleep often has a beneficial impact on these consequences. However, even after adequate and optimized treatment with continuous positive airway pressure (CPAP), about 6 to 10% of patients still remain sleepy. Given the high prevalence of OSA, this percentage represents a large number of under-treated and at-risk individuals. This residual excessive sleepiness (RES) may be related to comorbidities and cognitive alterations. Its physiopathology is still unknown. A few studies have tested modafinil as an adjunct treatment for RES patients. Since a) CPAP is ineffective in patients with RES; b) previous studies suggest some benefit with wake promoters; and c) cognitive impairment has also been reported associated with RES; the hypothesis of the present study is that donepezil improves alertness and cognition in patients with OSA and RES, evidencing the role of the cholinergic system in the pathophysiology of RES.

Objective: To evaluate the effects of donepezil on RES in adult patients treated with CPAP.

Thirty-six patients diagnosed with OSA and RES are estimated to be included. Participants will be treated with CPAP for more than 6 months with a mean use greater than 5 hours per day. After blood and cerebrospinal fluid collection, patients will be randomized into 2 groups of 30 days of treatment with donepezil or placebo. RES will be evaluated by the vigilance test and the Epworth Sleepiness Scale.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ksdy Maiara Werli, Psy; Phone Number: +55-11-958491512; Email: ksdymaiara@yahoo.com.br
• Study Contact Backup: Name: Dalva Poyares, MD; Phone Number: +55-11-985937418; Email: poyares@unifesp.br

Study Locations

• Brazil
  • Sao Paulo, Brazil, 04024-002
    • Instituto do Sono

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Both gender, Age between 35 and 65 years;
• Confirmed diagnosis of moderate to severe OSA;
• Treatment with CPAP for at least six months;
• Persistent sleepiness with daily CPAP use compliance > 5 hours per night.

Exclusion Criteria:

• Neurological or psychiatric diseases;
• Chronic use of psychoactive drugs, other sleep disorders than OSA, visual defficiency, illiteracy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: donepezil treatment; donepezil with 10 mg will be administered for 30 days.	Drug: donepezil treatment; 30-day donepezil treatment
PLACEBO_COMPARATOR: placebo treatment; placebo with 10 mg placebo will be administered for 30 days.	Drug: donepezil treatment; 30-day donepezil treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective excessive daytime sleepiness	Maintenance Wakefulness Test	40 days
subjective excessive daytime sleepiness	Epworth Sleepiness Scale	40 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cognitive improvement (executive functions)	standard cognitive tests to evaluate executive functions	40 days

Collaborators and Investigators

• Sponsor: Associação Fundo de Incentivo à Pesquisa

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 6, 2018
• Primary Completion (ANTICIPATED): November 4, 2018
• Study Completion (ANTICIPATED): March 2, 2019

Study Registration Dates

• First Submitted: May 11, 2017
• First Submitted That Met QC Criteria: September 27, 2017
• First Posted (ACTUAL): October 3, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 27, 2018
• Last Update Submitted That Met QC Criteria: June 26, 2018
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: OSA; CPAP; donepezil; sleepiness
• Additional Relevant MeSH Terms: Sleepiness; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: RES12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No