Clinical trial NCT03299257: Donepezil, Residual Excessive Daytime Sleepiness, Obstructive Sleep Apnea
Official title: Donepezil for Residual Symptoms in CPAP Treated Obstructive Sleepapnea Patients: A Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: OSA
Sleepiness
Keywords: OSA
CPAP
sleepiness
donepezil
Lead sponsor: Associação Fundo de Incentivo à Pesquisa
Sponsor class: OTHER
First posted: 2017-10-03
Enrollment: 36
Sex: ALL
Minimum age (years): 35
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, parallel groups, 30-day trial
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: objective excessive daytime sleepiness
timeFrame: 40 days
measure: subjective excessive daytime sleepiness
timeFrame: 40 days
Secondary outcomes:
measure: cognitive improvement (executive functions)
timeFrame: 40 days
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Instituto do Sono
Study officials:
References: