Effects of Donepezil and Memantine on Cognitive Functions After a Sleep Deprivation Challenge in Healthy Volunteers
Condition: Healthy
MeSH terms: Sleep Deprivation
Study type: Interventional
Phase: Phase 1

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.
    

Detailed 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
    

Intervention name(s): Modafinil; Donepezil; Memantine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 200 mg tablet, single dose; Donepezil or placebo, 5 mg tablet one per day, 15 days; Memantine or placebo, 10 mg tablet one per day, 15 days
Intervention MeSH terms: Memantine; Modafinil; Donepezil
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Keywords: Sleep deprivation; Cognitive Functions; young male