Donepezil Versus Non-drug Treatment in Alzheimer's Disease.

Alzheimer Disease, Early Onset Clinical Trial

— CHOLINE-2  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04661280
• Other study ID #: APHP201183
• Status: Recruiting
• Phase: Phase 3
• Start date: February 10, 2022
• Est. completion date: August 2026

Study information

• Verified date: November 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: DUMURGIER Julien, MD, PhD
• Phone: +33140054313
• Email: julien.dumurgier[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: August 2026
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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 Aß42 in the CSF or Aß40 / Aß42 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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer Disease, Early Onset

Intervention

Drug:
• Donepezil
Donepezil 5 mg per day during one month, then 10 mg per day during 5 months.

Locations

Country	Name	City	State
France	Cognitive Neurology Center	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	France Alzheimer

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	26 weeks
Secondary	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	26 weeks
Secondary	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	26 weeks
Secondary	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	26 weeks
Secondary	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).	26 weeks
Secondary	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	26 weeks