ClinicalTrials.Veeva

Menu

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

Q

Qualissima

Status and phase

Completed
Phase 1

Conditions

Healthy

Treatments

Drug: Memantine
Drug: Modafinil
Drug: Donepezil

Study type

Interventional

Funder types

Other

Identifiers

NCT01461174
WP1P001
2011-000344-25 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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

Enrollment

36 patients

Sex

Male

Ages

25 to 40 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Demography

  1. Healthy male subjects aged between 25 and 40 years-old inclusive

  2. BMI between 18 kg/m2 to 27 kg/m2

    Health status

  3. The subjects is in good health on the basis of the medical interview (medical history, symptoms) and the physical examination, vital signs and the results of blood chemistry and hematology.

  4. ECG (12 leads) normal (120 < PR < 200 ms; QRS < 120ms; QTcF < 450ms) and/or without clinically relevant impairments as judged by investigator.

  5. The subject does not smoke or smokes a maximum of 5 cigarettes per day and is able to stop during the days of the study.

  6. No claustrophobia (fMRI)

  7. The subject has normal visual and auditory abilities

    Specific to the study

  8. Habitual good sleeping: sleeping on average 6,5 to 9 hours each night in the past month assessed by the Pittsburgh Quality Index.

  9. Regular sleeping hours whereby they sleep no later than 1 am and rise before 9 am in the past month assessed by the Pittsburgh Quality Index.

  10. The subject can complete the neuropsychological test battery during the training session

  11. The subject corresponds to an extravert personality according to the Eysenck Personality Inventory

  12. The subject is right-handed (Edinburgh Handedness Inventory, Imaging measurement condition).

    Regulations

  13. The subjects is able to read and understand the Information Form and comply with the protocol instructions and restrictions

  14. Subjects are covered by a social insurance

  15. Subjects have provided written informed consent

Exclusion criteria

Medical history and clinical status

  1. History or presence of psychiatric illness assessed by a psychiatric interview with the Mini-International Neuropsychiatric Interview (M.I.N.I-DSM IV).

  2. History or presence of neurologic illness or others illnesses (general medical interview)

  3. The subject has caffeine intake of greater than 5 drinks per day or excessive energy drink type intake.

  4. The subject has an orthostatic blood pressure reduction > 20 mm Hg, based on a difference of systolic blood pressure between supine and after standing for 3 minutes.

    General conditions

  5. The patient, in the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any other reason

  6. The subject participates to another clinical trial or is still being within a washout period of a previous clinical trial, or subjects who received more than 4500 euros in the previous 12 months.

    Specific to the study

  7. History or presence of daytime sleepiness with the Epworth scale (score > 10, pathological sleepiness).

  8. History of obstructive sleep apnea assessed by the Berlin questionnaire.

  9. History of periodic leg movements assessed by Restless Legs Syndrome questionnaire.

  10. Extreme chronotypes: score at the Horne Ostberg scale (< 31 or > 69).

  11. Jet lag > 2 hours in the last two weeks.

  12. No time-shifted work during the last month.

Trial design

36 participants in 3 patient groups

Modafinil
Experimental group
Description:
200 mg tablet, single dose
Treatment:
Drug: Modafinil
Donepezil
Experimental group
Description:
5 mg tablet one per day, 15 days
Treatment:
Drug: Donepezil
Memantine
Experimental group
Description:
10 mg tablet one per day, 15 days
Treatment:
Drug: Memantine

Trial contacts and locations

2

Loading...

Data sourced from clinicaltrials.gov

Clinical trials

Find clinical trialsTrials by location
© Copyright 2025 Veeva Systems