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

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

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

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.

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