HealthyPhase 1NCT01461174
Effects of Donepezil and Memantine on Cognitive Functions After a Sleep Deprivation Challenge in Healthy Volunteers
A Phase 1 study testing Modafinil, Donepezil and Memantine in people with Healthy, run by Qualissima at 2 sites in France.
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. Read more about this study
- Who is it for?
- Ages 25 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Modafinil, Donepezil and Memantine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 2 sitesFrance
- Study dates
- Nov 2011to Nov 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Demography
- Healthy male subjects aged between 25 and 40 years-old inclusive
- BMI between 18 kg/m2 to 27 kg/m2
- Health status
- 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.
- ECG (12 leads) normal (120 < PR < 200 ms; QRS < 120ms; QTcF < 450ms) and/or without clinically relevant impairments as judged by investigator.
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- 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.
- No claustrophobia (fMRI)
- The subject has normal visual and auditory abilities
- Specific to the study
- Habitual good sleeping: sleeping on average 6,5 to 9 hours each night in the past month assessed by the Pittsburgh Quality Index.
- 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.
- The subject can complete the neuropsychological test battery during the training session
- The subject corresponds to an extravert personality according to the Eysenck Personality Inventory
- The subject is right-handed (Edinburgh Handedness Inventory, Imaging measurement condition).
- Regulations
- The subjects is able to read and understand the Information Form and comply with the protocol instructions and restrictions
- Subjects are covered by a social insurance
- Subjects have provided written informed consent
Who cannot join
- Medical history and clinical status
- History or presence of psychiatric illness assessed by a psychiatric interview with the Mini-International Neuropsychiatric Interview (M.I.N.I-DSM IV).
- History or presence of neurologic illness or others illnesses (general medical interview)
- The subject has caffeine intake of greater than 5 drinks per day or excessive energy drink type intake.
- 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
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- The patient, in the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any other reason
- 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
- History or presence of daytime sleepiness with the Epworth scale (score > 10, pathological sleepiness).
- History of obstructive sleep apnea assessed by the Berlin questionnaire.
- History of periodic leg movements assessed by Restless Legs Syndrome questionnaire.
- Extreme chronotypes: score at the Horne Ostberg scale (< 31 or > 69).
- Jet lag > 2 hours in the last two weeks.
- No time-shifted work during the last month.
Trial locations and contacts
2 sites in 1 country.
About this study
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
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.
Read the 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
- Conditions
- Healthy
- Being tested
- Modafinil, Donepezil, Memantine
- Keywords
- Sleep deprivation, Cognitive Functions, young male
- Medical subject headings
- Sleep Deprivation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ModafinilDrug
200 mg tablet, single dose
DonepezilDrug
Donepezil or placebo, 5 mg tablet one per day, 15 days
MemantineDrug
Memantine or placebo, 10 mg tablet one per day, 15 days
| Study group | Role | What they receive |
|---|---|---|
| Modafinil | Experimental | 200 mg tablet, single dose Receives: Drug: Modafinil |
| Donepezil | Experimental | 5 mg tablet one per day, 15 days Receives: Drug: Donepezil |
| Memantine | Experimental | 10 mg tablet one per day, 15 days Receives: Drug: Memantine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in N-back
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.
Measured: Day 1 and Day 2 for each of the 5 Period
Secondary outcomes (3)
Other cognitive assessments
CANTAB Battery, Memory Rey Auditory Verbal Learning Test (AVLT), Digit Span Test, Verbal Fluency task
Measured: Day 1 and Day 2 for each of the 5 Period
fMRI
Resting fMRI, fMRI Memory task
Measured: Day 1 and Day 2 for each of the 5 Period
Rest-EEG and P300 after auditory-ball paradigm Rest-EEG and P300 after auditory-ball paradigm Rest-EEG and P300 after auditory-ball paradigm
Rest-EEG and P300 after auditory-ball paradigm
Measured: Day 1 and Day 2 for each of the 5 Period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2011 (estimated)
- Study startNov 2011
- Primary completionNov 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Qualissima
- Sponsor type
- University, hospital or other
- Collaborators
- European Union
- Responsible party
- Sponsor
- Investigators
- Christine Audebert, Principal investigator, CIC CPCET
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01461174
- Sponsor's protocol ID
- WP1P001
- Other IDs
- 2011-000344-25
- Status last verified
- Feb 2015
- First submitted
- 17 Oct 2011
- Last updated
- 4 Feb 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01461174
- Acronym / sponsor ID
- WP1P001
- Conditions
- Healthy
- Keywords
- Sleep deprivation, Cognitive Functions, young male
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- QualissimaUniversity, hospital or other
- Collaborators
- European Union
- Study start
- Nov 2011
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 27 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Modafinil | Experimental | Drug: Modafinil200 mg tablet, single dose |
| Donepezil | Experimental | Drug: Donepezil5 mg tablet one per day, 15 days |
| Memantine | Experimental | Drug: Memantine10 mg tablet one per day, 15 days |
Who may qualify
- Ages
- 25 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- Demography
- Healthy male subjects aged between 25 and 40 years-old inclusive
- BMI between 18 kg/m2 to 27 kg/m2
- Health status
- 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.
Key exclusion criteria (15 listed)
- Medical history and clinical status
- History or presence of psychiatric illness assessed by a psychiatric interview with the Mini-International Neuropsychiatric Interview (M.I.N.I-DSM IV).
- History or presence of neurologic illness or others illnesses (general medical interview)
- The subject has caffeine intake of greater than 5 drinks per day or excessive energy drink type intake.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Modafinil200 mg tablet, single dose | Drug | Modafinil |
| DonepezilDonepezil or placebo, 5 mg tablet one per day, 15 days | Drug | Donepezil |
| MemantineMemantine or placebo, 10 mg tablet one per day, 15 days | Drug | Memantine |
Primary outcome
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.
3 secondary outcomes
Other cognitive assessments
Time frame: Day 1 and Day 2 for each of the 5 Period
fMRI
Time frame: Day 1 and Day 2 for each of the 5 Period
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christine Audebert principal investigator
CIC CPCET
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Modafinil, Donepezil and Memantine in people with Healthy, run by Qualissima at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in N-back (time frame: Day 1 and Day 2 for each of the 5 Period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2015.