Effects of Donepezil and Memantine on Cognitive Functions After a Sleep Deprivation Challenge in Healthy Volunteers

Healthy Clinical Trial

Official title: Effects of 15-day Donepezil and Memantine on Cognitive Functions After a 24 Hours Sleep Deprivation Challenge in Healthy Volunteers: a Double-blind, Placebo-controlled, Randomised, Cross-over Study, With Modafinil as Positive Control

Status Completed

Clinical Trial Summary

The aim of this study is to assess the utility of sleep deprivation as a potential model for prediction of clinical efficacy using a combination of cognitive physiological endpoints.

Clinical Trial Description

BACKGROUND:

With the inherent difficulty of detecting significant improvements in cognitive performance in normal healthy subjects, it is presently incredibly hard to predict and select efficacious agents early in the drug development process. As such the potential success of novel therapeutic agents for the symptomatic relief of Alzheimer's disease (AD) is largely unknown until the drugs enter relatively large studies, assessing clinical outcome over at least a six month period. To try to overcome this issue, clinical scientists have focused their attention to the development of cognitive endpoints/biomarkers that can be detected in a number of experimental paradigms where cognitive impairments akin to those observed in AD, have been artificially induced.Based on the scientific literature, the use of total Sleep Deprivation in healthy volunteers seems to be a good paradigm to assess potential anti-AD agents.

It is the first multicenter study that combines 3 complementary approaches via a standardization of the sleep deprivation model: cognitive evaluations, imaging and neurophysiology.

STUDY OBJECTIVE(S)

Primary:

The study aim is to assess the utility of sleep deprivation as a potential model for prediction of clinical efficacy using a combination of cognitive physiological endpoints.

The main goals are to test the effects of donepezil and memantine treatment on cognitive functions in young healthy deprived subjects and to assess the potential restoring effect of the two drugs on cognitive functions induce by sleep deprivation.

Secondary:

• To assess that Sleep Deprivation model results in cognitive impairments

• To determine the sensitivity of the model by testing the restoring effects of one single dose of modafinil

• To investigate the reversal effect of modafinil on EEG under sleep deprivation.

• To investigate the reversal effect of modafinil on fMRI acquisitions under sleep deprivation (subjects that will be included in Toulouse will not have fMRI)

• To investigate the influence of donepezil and memantine on EEG under sleep deprivation.

• To investigate the influence of donepezil and memantine on fMRI acquisitions under sleep deprivation (subjects that will be included in Toulouse will not have fMRI).

STUDY DESIGN The study is a phase I, multicentric (Lille, Marseille, Toulouse), randomised, placebo-controlled, cross-over design.

STUDY POPULATION Healthy young male subjects from 25 to 40 years-old (36 subjects randomized)

PRIMARY ENDPOINT(S) AND MAIN SECONDARY ENDPOINT(S)

Primary endpoint:

N-back test

Secondary endpoints:

• Other cognitive assessments

• Imaging

• Neurophysiology ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Healthy
• Sleep Deprivation

• NCT number: NCT01461174
• Study type: Interventional
• Source: Qualissima
• Status: Completed
• Phase: Phase 1
• Start date: November 2011
• Completion date: November 2014