Alzheimer Disease, Early OnsetPhase 3CHOLINE-2NCT04661280
Donepezil Versus Non-drug Treatment in Alzheimer's Disease.
A Phase 3 study testing Donepezil in people with Alzheimer Disease, Early Onset, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Donepezil, as well as the other symptomatic drugs of Alzheimer's disease, is not any more reimbursed by the French healthcare system, due to a controversy about its efficiency. French health authorities currently preconize a non-rug approach based on cognitive remediation or stimulation. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Alzheimer Disease, Early Onset
- What is being tested?
- Donepezil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 1 siteFrance
- Study dates
- 10 Feb 2022to Aug 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of Alzheimer's disease according to the IWG-2 criteria.
- Age ≥ 50 years.
- Absence of legal protection measures (guardianship, curatorship).
- MMSE score ≥ 10 at inclusion.
- abnormal values for Aβ42 in the CSF or Aβ40 / Aβ42 ratio.
- abnormal values for phosphorylated Tau in CSF
- Presence of a family carer or a person at home who can ensure compliance with treatment if MMSE score <20.
- French native speaker.
Who cannot join
- Other cause of dementia.
- Previous use of symptomatic treatment for Alzheimer's disease.
- Hypersensitivity to donepezil hydrochloride or to any of the excipients listed in the SPC.
- Cardiological contraindication after possible opinion of a cardiologist, at the initiative of the investigator, in particular bradycardia, sinus disease or other supra-ventricular conduction abnormalities such as sinoatrial or atrioventricular block.
- Taking concomitant medications known to prolong the interval QTc
- Patients at particular risk of ulcer, known ulcer disease or receiving concomitant treatment with non-steroidal anti-inflammatory drugs.
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- Patient at risk of urinary retention.
- History of epileptic disease.
- History of neuroleptic malignant syndrome.
- History of asthma or obstructive bronchopulmonary disease.
- Severe hepatic impairment.
- Taking one of the following treatments:
- CYP3A4 inhibitors, such as ketonazole.
- 2D6 inhibitors, such as quinidine.
- CYP3A4 inhibitors, such as itraconazole and erythromycin.
- CYP2D6 inhibitors, such as fluoxetine.
- Enzyme inducers such as rifampicin, phenytoin, carbamazepine.
- Antiarrhythmic class IA agents
- Antiarrhythmic class III agents
- other Antipsychotics such as phenothiazine, sertindole, pimozide, ziprasidone.
- some antiobiotics such as clarithromycine, erythromycine, levofloxacine, moxifloxacine.
- Participation in another interventional study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
PAQUET Claire, MD, PhD contact
France1 site, 1 recruiting
- Recruiting
Cognitive Neurology Center
Paris, 75010
DUMURGIER Julien, MD, PhD, +33140054313, julien.dumurgier@aphp.fr
About this study
Official title: Donepezil Use Versus Non-drug Approach in Treatment of Newly Diagnosed Alzheimer's Disease : a Multicentric, Randomized, Open Study : the CHOLINE-2 Study
Donepezil, as well as the other symptomatic drugs of Alzheimer's disease, is not any more reimbursed by the French healthcare system, due to a controversy about its efficiency. French health authorities currently preconize a non-rug approach based on cognitive remediation or stimulation.
The aim of this study is to compare the efficiency of the 2 approaches (non-drug versus donepezil) on the symptoms of Alzheimer's disease after 6 months of treatment.
Read the detailed description
Randomized multicentric open-label study, comparison of 2 therapeutic strategies.
2 arms:
- Standard of care, non-drug approach: following the recommendations of the Alzheimer's disease care by the Frenchh Health Authority. The care is cognitive, psychic, functional or social and centered on the patient and his environment. This care is best carried out by the memory consultations participating in this study and having extensive experience in the care of Alzheimer patients. It is usually based in particular on the prescription of cognitive stimulation sessions by a speech therapist and a mobile Alzheimer specialist team at home for cognitive remediation sessions.
- Donepezil group: Management similar to the previous arm plus addition of Donepezil 5 mg per os once a day for one month and then 10 mg per os once a day until the 6th month.
- Conditions
- Alzheimer Disease, Early Onset
- Being tested
- Donepezil
- Keywords
- Alzheimer Disease, Donepezil
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DonepezilDrug
Also called Aricept
Donepezil 5 mg per day during one month, then 10 mg per day during 5 months.
| Study group | Role | What they receive |
|---|---|---|
| Cognitive remediation | No intervention | Non-drug treatment, cognitive remediation, cognitive stimulation |
| Cognitive remediation + Donepezil | Experimental | Non-drug treatment, cognitive remediation, cognitive stimulation + Donepezil Receives: Drug: Donepezil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference of change in the MMSE score
Difference of change in the MMSE score between baseline and 26 weeks in the 2 ams (donepezil versus non-drug). MMSE is measured at baseline, 6 weeks, 13 weeks, and 26 weeks.
Measured: 26 weeks
Secondary outcomes (5)
Difference of change in the ADAS-Cog scale
Difference of change in the ADAS-Cog scale between baseline and 26 weeks in the 2 ams (donepezil versus non-drug).
ADAS-Cog scale = Alzheimer's Disease Assessment Scale-Cognitive Subscale, scored from 0 to 70
Measured: 26 weeks
Difference of change in the CDR scale
Difference of change in the CDR scale between baseline and 26 weeks in the 2 ams (donepezil versus non-drug).
CDR scale = Clinical Dementia Rating, scored from 0 to 3
Measured: 26 weeks
Difference of change in the ADL scale
Difference of change in the ADL scale between baseline and 26 weeks in the 2 ams (donepezil versus non-drug).
ADL scale = Autonomy scale on daily activities, scored from 0 to 78
Measured: 26 weeks
Difference of change in the quality of life scale
Difference of change in the quality of life scale between baseline and 26 weeks in the 2 ams (donepezil versus non-drug).
Measured: 26 weeks
Difference of change in the ZARIT scale
Difference of change in the ZARIT scale between baseline and 26 weeks in the 2 ams (donepezil versus non-drug).
ZARIT scale = for assessing caregiver burden, scored from 0 to 88
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2020
- Study start10 Feb 2022
- Primary completionAug 2026 (estimated)
- Study completionAug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer Disease, Early OnsetStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- France Alzheimer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04661280
- Sponsor's protocol ID
- APHP201183
- Acronym
- CHOLINE-2
- Status last verified
- Feb 2026
- First submitted
- 3 Dec 2020
- Last updated
- 18 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Donepezil Use Versus Non-drug Approach in Treatment of Newly Diagnosed Alzheimer's Disease : a Multicentric, Randomized, Open Study : the CHOLINE-2 Study
- ClinicalTrials.gov ID
- NCT04661280
- Acronym / sponsor ID
- CHOLINE-2 / APHP201183
- Conditions
- Alzheimer Disease, Early Onset
- Keywords
- Alzheimer Disease, Donepezil
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- France Alzheimer
- Study start
- 10 Feb 2022 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Aug 2026 (estimated)
- First posted
- 10 Dec 2020 (actual)
- 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.
Donepezil, as well as the other symptomatic drugs of Alzheimer's disease, is not any more reimbursed by the French healthcare system, due to a controversy about its efficiency. French health authorities currently preconize a non-rug approach based on cognitive remediation or stimulation.
The aim of this study is to compare the efficiency of the 2 approaches (non-drug versus donepezil) on the symptoms of Alzheimer's disease after 6 months of treatment.
Detailed description
Randomized multicentric open-label study, comparison of 2 therapeutic strategies.
2 arms:
- Standard of care, non-drug approach: following the recommendations of the Alzheimer's disease care by the Frenchh Health Authority. The care is cognitive, psychic, functional or social and centered on the patient and his environment. This care is best carried out by the memory consultations participating in this study and having extensive experience in the care of Alzheimer patients. It is usually based in particular on the prescription of cognitive stimulation sessions by a speech therapist and a mobile Alzheimer specialist team at home for cognitive remediation sessions.
- Donepezil group: Management similar to the previous arm plus addition of Donepezil 5 mg per os once a day for one month and then 10 mg per os once a day until the 6th month.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cognitive remediation | No intervention | –Non-drug treatment, cognitive remediation, cognitive stimulation |
| Cognitive remediation + Donepezil | Experimental | Drug: DonepezilNon-drug treatment, cognitive remediation, cognitive stimulation + Donepezil |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosis of Alzheimer's disease according to the IWG-2 criteria.
- Age ≥ 50 years.
- Absence of legal protection measures (guardianship, curatorship).
- MMSE score ≥ 10 at inclusion.
- abnormal values for Aβ42 in the CSF or Aβ40 / Aβ42 ratio.
Key exclusion criteria (22 listed)
- Other cause of dementia.
- Previous use of symptomatic treatment for Alzheimer's disease.
- Hypersensitivity to donepezil hydrochloride or to any of the excipients listed in the SPC.
- Cardiological contraindication after possible opinion of a cardiologist, at the initiative of the investigator, in particular bradycardia, sinus disease or other supra-ventricular conduction abnormalities such as sinoatrial or atrioventricular block.
- Taking concomitant medications known to prolong the interval QTc
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 |
|---|---|---|
| DonepezilAlso: AriceptDonepezil 5 mg per day during one month, then 10 mg per day during 5 months. | Drug | Cognitive remediation + Donepezil |
Primary outcome
Difference of change in the MMSE score
Time frame: 26 weeks
Difference of change in the MMSE score between baseline and 26 weeks in the 2 ams (donepezil versus non-drug). MMSE is measured at baseline, 6 weeks, 13 weeks, and 26 weeks.
5 secondary outcomes
Difference of change in the ADAS-Cog scale
Time frame: 26 weeks
Difference of change in the CDR scale
Time frame: 26 weeks
Difference of change in the ADL scale
Time frame: 26 weeks
Difference of change in the quality of life scale
Time frame: 26 weeks
Difference of change in the ZARIT scale
Time frame: 26 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2026.
- Individual participant dataSharing planned: No
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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.
PAQUET Claire, MD, PhD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Donepezil in people with Alzheimer Disease, Early Onset, run by Assistance Publique - Hôpitaux de Paris at 1 site 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 8 inclusion and 22 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: looking for participants now, as of the sponsor's last update on 18 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact DUMURGIER Julien, MD, PhD (+33140054313, julien.dumurgier@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference of change in the MMSE score (time frame: 26 weeks). 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 18 Feb 2026.