Donepezil Versus Non-drug Treatment in Alzheimer's Disease. (CHOLINE-2)

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.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease, Early Onset
• Intervention / Treatment: Drug: Donepezil

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 Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: DUMURGIER Julien, MD, PhD; Phone Number: +33140054313; Email: julien.dumurgier@aphp.fr
• Study Contact Backup: Name: PAQUET Claire, MD, PhD; Email: claire.paquet@inserm.fr

Study Locations

• France
  • Paris, France, 75010
    • Recruiting
    • Cognitive Neurology Center
    • Contact: DUMURGIER Julien, MD, PhD; Phone Number: +33140054313; Email: julien.dumurgier@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Cognitive remediation; Non-drug treatment, cognitive remediation, cognitive stimulation
Experimental: Cognitive remediation + Donepezil; Non-drug treatment, cognitive remediation, cognitive stimulation + Donepezil	Drug: Donepezil; Donepezil 5 mg per day during one month, then 10 mg per day during 5 months.; Other Names: Aricept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: France Alzheimer

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: December 3, 2020
• First Submitted That Met QC Criteria: December 3, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer Disease; Donepezil
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: APHP201183

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No