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

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ClinicalTrials.gov Identifier: NCT01461174
Recruitment Status : Completed
First Posted : October 27, 2011
Last Update Posted : February 4, 2015
Sponsor:
Collaborator:
European Union
Information provided by (Responsible Party):
Qualissima

Tracking Information
First Submitted Date  ICMJE October 17, 2011
First Posted Date  ICMJE October 27, 2011
Last Update Posted Date February 4, 2015
Study Start Date  ICMJE November 2011
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2011)
Change in N-back [ Time Frame: Day 1 and Day 2 for each of the 5 Period ]
The N-back test is both sensitive to SD in healthy volunteers and this test belongs to ADNI cognitive battery which is validated in Alzheimer's disease patients,considered as primary endpoint.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2011)
  • Other cognitive assessments [ Time Frame: Day 1 and Day 2 for each of the 5 Period ]
    CANTAB Battery, Memory Rey Auditory Verbal Learning Test (AVLT), Digit Span Test, Verbal Fluency task
  • fMRI [ Time Frame: Day 1 and Day 2 for each of the 5 Period ]
    Resting fMRI, fMRI Memory task
  • Rest-EEG and P300 after auditory-ball paradigm Rest-EEG and P300 after auditory-ball paradigm Rest-EEG and P300 after auditory-ball paradigm [ Time Frame: Day 1 and Day 2 for each of the 5 Period ]
    Rest-EEG and P300 after auditory-ball paradigm
Original Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2011)
  • Other cognitive assessments [ Time Frame: Day 1 and Day 2 for each of the 5 Period ]
    CANTAB Battery, Memory Rey Auditory Verbal Learning Test (AVLT), Digit Span Test, Verbal Fluency task
  • fMRI [ Time Frame: Day 1 and Day 2 for each of the 5 Period ]
    Resting fMRI, fMRI Memory task
  • Neurophysiology [ Time Frame: Day 1 and Day 2 for each of the 5 Period ]
    Rest-EEG and P300 after auditory-ball paradigm
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Donepezil and Memantine on Cognitive Functions After a Sleep Deprivation Challenge in Healthy Volunteers
Official Title  ICMJE 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
Brief 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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Condition  ICMJE Healthy
Intervention  ICMJE
  • Drug: Modafinil
    200 mg tablet, single dose
  • Drug: Donepezil
    Donepezil or placebo, 5 mg tablet one per day, 15 days
  • Drug: Memantine
    Memantine or placebo, 10 mg tablet one per day, 15 days
Study Arms  ICMJE
  • Experimental: Modafinil
    200 mg tablet, single dose
    Intervention: Drug: Modafinil
  • Experimental: Donepezil
    5 mg tablet one per day, 15 days
    Intervention: Drug: Donepezil
  • Experimental: Memantine
    10 mg tablet one per day, 15 days
    Intervention: Drug: Memantine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 25, 2011)
36
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2014
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 25 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01461174
Other Study ID Numbers  ICMJE WP1P001
2011-000344-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Qualissima
Study Sponsor  ICMJE Qualissima
Collaborators  ICMJE European Union
Investigators  ICMJE
Principal Investigator: Christine Audebert CIC CPCET
PRS Account Qualissima
Verification Date February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP