Prediction of Cognitive Properties of New Drug Candidates for Neurodegenerative Diseases in Early Clinical Development

Study Overview
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Brief Summary
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The early assessment of new drugs for Alzheimer's disease remains difficult because of the lack of predictive end-point. The use of a battery including different parameters could improve this early development of new drugs. Nevertheless, the interest of such a battery should previously be validated with the yet marketed AD drugs

Detailed Description
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The aim of the present study is to test the effect of a 15-day treatment with donepezil on a mixed battery associating cognitive assessment, imaging and neurophysiological tests in healthy volunteers. This multicenter, randomized, placebo-controlled, cross-over study is double-blind controlled and is conducted in 3 centers located in France (Lille, Marseille and Toulouse). 18-30 years old, healthy volunteers, without any neurological or psychiatric impairment, will complete 2 test sessions in a randomized order: one with a 15-day treatment with donepezil, the other with placebo, and will be submitted to a mixed battery during the 14th and 15th day of the treatment. The primary outcome of the study will be based on cognitive assessment, imaging parameters and neurophysiological parameters.

Official Title
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Effect of a 15-day Donepezil Treatment on Biomarkers of AD in Healthy Volunteers

Conditions
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Alzheimer Disease, Battery

Intervention / Treatment
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* Drug: Donepezil .
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-30 year old male non-smoker subjects Subject without cognitive impairment or cognitive complaint (Moca>26, Mac Nair scale<15) Subject without history of brain disease (severe brain trauma, stroke, cerebral tumor,…) Subject without major medical or surgical history Subject without current chronic disease Subject without current cerebral disease Subject without vascular or metabolic risk factor Subject without history or current mental disease or addiction (MINI) Subject without lesion on MRI Subject without abnormal electrical activities on EEG Subject without use of chronic treatment or psychotropic drugs or substances French speaker subject and able to understand the test instructions Exclusion Criteria: Subject with age < 18 years or > 30 years Subject with dementia or cognitive decline identified by Moca < 26 Subject with history of brain disease (brain trauma, stroke, cerebral tumor,…) Subject with major medical or surgical history Subject with current chronic disease Subject with current cerebral disease Subject with vascular or metabolic risk factor Subject with history or current mental disease or addiction Subject with family history of young-onset dementia Subject with family history of chronic or severe neurological or mental disease (first degree relatives) Subject with lesion on MRI Subject with abnormal electrical activities on EEG Subject receiving a chronic treatment Subject using chronically or acutely psychotropic drugs or substances Subject with claustrophobia or contra-indication to MRI Subject unable to understand the test instructions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Donepezil<br>Donepezil will be administered OS as of 5 mg- Orally Disintegrating Tablets one per day in the morning over 15 days. | Drug: Donepezil .<br>* Donepezil will be administered OS as of 5 mg- Orally Disintegrating Tablets one per day in the morning over 15 days.<br>* Other names: Orally Disintegrating Tablets (ODT): 5 mg.;|
| Placebo Comparator: Placebo<br>The placebo will be presented as tablet comparable to ARICEPT | Drug: Placebo<br>* the placebo will be administered OS as of 5 mg- Orally Disintegrating Tablets one per day in the morning over 15 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacog battery | cognitive tests (8 items of the Cantab battery) : Motor screening 4 tests for visual memory (Delayed Matching to Sample, Paired Associated Learning, Pattern Recognition Memory, Spatial Recognition Memory) 1 test for executive functions (Spatial Working Memory) 2 tests for attention (Reaction Time, Rapid Visual Information Processing) completed by a modified ADNI battery : ADAScog imaging fMRI PET-FDG neurophysiological EEG | 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer, Donepezil, biomarkers, battery, cognition, imaging, neurophysiological