Clinical trial NCT04661280: Donepezil Versus Non-drug Treatment in Alzheimer's Disease.
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Alzheimer Disease, Early Onset
Keywords: Alzheimer Disease
Donepezil
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: France Alzheimer
First posted: 2020-12-10
Enrollment: 240
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
measure: Difference of change in the MMSE score
timeFrame: 26 weeks
Secondary outcomes:
measure: Difference of change in the ADAS-Cog scale
timeFrame: 26 weeks
measure: Difference of change in the CDR scale
timeFrame: 26 weeks
measure: Difference of change in the ADL scale
timeFrame: 26 weeks
measure: Difference of change in the quality of life scale
timeFrame: 26 weeks
measure: Difference of change in the ZARIT scale
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Paris
country: France
facility: Cognitive Neurology Center
Study officials:
References: