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

Phase 1

Completed

• Conditions: Alzheimer Disease; Battery
• Interventions: Drug: Placebo; Drug: Donepezil .

• Registration Number: NCT01487395
• Lead Sponsor: University Hospital, Lille

Brief Summary

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

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.

Study Timeline

• Study Start: 2011-12
• Study First Submitted: 2011-12-05
• Study First Submitted QC: 2011-12-06
• Study First Posted: 2011-12-07
• Primary Completion: 2012-12
• Study Completion: 2013-12
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-08
• Last Update Posted: 2015-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	The placebo will be presented as tablet comparable to ARICEPT
Donepezil	Donepezil .	Donepezil will be administered OS as of 5 mg- Orally Disintegrating Tablets one per day in the morning over 15 days.

Primary Outcome Measures

Name	Time	Method
Pharmacog battery	15 days	* 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

Trial Locations

Locations (3)

CHRU de Lille/ Centre d'investigation Clinique; 🇫🇷 Lille, France

CIC Marseille; 🇫🇷 Marseille, France

CIC Toulouse; 🇫🇷 Toulouse, France