Clinical trial NCT00480870: The Effect of Anticholinesterase Drugs on Sleep in Alzheimer's Disease Patients
Official title: The Effect of Anticholinesterase Drugs on Sleep in Alzheimer's Disease Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Alzheimer Disease
Sleep Apnea, Obstructive
Keywords: Alzheimer
polysomnography
REM sleep
donepezil
sleep apnea
oxygen saturation
Lead sponsor: Associacao Fundo de Incentivo a Psicofarmcologia
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2007-05-31
Enrollment: 65
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the effects of the anticholinesterase drug donepezil on sleep in Alzheimer disease patients. Sleep structure and respiratory parameters will be analyzed by polysomnography.

Detailed description: Central acting cholinesterase inhibitors are the first primary pharmacological treatment approved for Alzheimer disease, of which donepezil is the most frequently used. Multicenter studies have found little toxicity, and its side effects (diarrhea, nausea, vomiting, nightmares, among others) are mild and transient. According to the literature, cholinergic active drugs may be expected to affect REM (rapid eye movement) sleep. Another possible effect is related to respiratory parameters in patients with Alzheimer disease and obstructive sleep apnea. In fact, cholinergic activity influences the upper airway opening via central and peripheral mechanisms.

Intervention: Patients will be administered donepezil or placebo. The study has a randomized, double-blind placebo-controlled design. Complete polysomnography with REM sleep EEG spectral analysis and ADAS-cog scoring will be performed at baseline and after 3 and 6 months.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Alzheimer's disease based on the probability criteria of the Alzheimer's Disease and Related Disorders Association
* Rated 1 and 2 (mild to moderate level) on the Brazilian version of the Clinical Dementia Rating

Exclusion Criteria:

* Other causes of dementia
* Other severe medical or psychiatric disease
* Clinical indication of psychoactive drugs other than experimental drug

Primary outcomes:
measure: Polysomnography parameters: sleep structure, respiratory, limb movements
timeFrame: onset, 3 and 6 months of treatment
Secondary outcomes:
measure: Brain magnetic resonance imaging
timeFrame: onset
measure: laboratory tests: hematological evaluation, creatinine, vitamin B12-folic acid, thyroid hormones, GOT, GPT, GGT, bilirubin, fasting glycemia, venereal disease research test and urine sediment
timeFrame: onset
measure: electroencephalogram
timeFrame: onset
measure: Mini-mental state examination
timeFrame: onset
measure: IDATE
timeFrame: onset
measure: Frequency bands of scalp EEG areas: overall (average of all electrodes), frontal (F3, F4, F7, F8, Fz), temporal (T3, T4, T5, T6), parietal (P3, P4, Pz), central (C3, C4, Cz), and occipital (O1, O2, Oz).
timeFrame: onset, 3 and 6 months of treatment
measure: ADAS-cog scores
timeFrame: onset, 3 and 6 months of treatment
measure: Clinical Dementia Rating
timeFrame: onset
measure: EEG slowing ratio
timeFrame: onset, 3 and 6 monthes of treatment
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Instituto do Sono
Study officials:
affiliation: Associação Fundo de Incentivo a Psicofarmacologia - AFIP
name: Walter AS Moraes, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rosa A, Poyares D, Moraes W, Cintra F. Methodology in clinical sleep research. Cell Mol Life Sci. 2007 May;64(10):1244-53. doi: 10.1007/s00018-007-6535-y.
citation: Lucchesi LM, Pradella-Hallinan M, Lucchesi M, Moraes WA. [Sleep in psychiatric disorders]. Braz J Psychiatry. 2005 May;27 Suppl 1:27-32. doi: 10.1590/s1516-44462005000500006. Epub 2005 Jul 28. Portuguese.
citation: Moraes Wdos S, Poyares DR, Guilleminault C, Ramos LR, Bertolucci PH, Tufik S. The effect of donepezil on sleep and REM sleep EEG in patients with Alzheimer disease: a double-blind placebo-controlled study. Sleep. 2006 Feb;29(2):199-205. doi: 10.1093/sleep/29.2.199.
citation: McCleery J, Sharpley AL. Pharmacotherapies for sleep disturbances in dementia. Cochrane Database Syst Rev. 2020 Nov 15;11(11):CD009178. doi: 10.1002/14651858.CD009178.pub4.
citation: Moraes W, Poyares D, Sukys-Claudino L, Guilleminault C, Tufik S. Donepezil improves obstructive sleep apnea in Alzheimer disease: a double-blind, placebo-controlled study. Chest. 2008 Mar;133(3):677-83. doi: 10.1378/chest.07-1446. Epub 2008 Jan 15.