Randomized Clinical Trial of Donepezil for the Treatment of Mild Cognitive Impairment in Parkinson's Disease

Multicenter, Randomized, Double-blinded, Placebo-controlled Clinical Trial of Donepezil for the Treatment of Mild Cognitive Impairment in Parkinson's Disease

Phase II, multi-centric, randomized, double-blinded, placebo-controlled, parallel design clinical trial to evaluate the safety, tolerability and efficacy of Donepezil in patients with Mild Cognitive Impairment in Parkinson's Disease (PD-MCI). A total of 120 patients with PD-MCI will be randomized to 12 months of oral Donepezil 10mg or matching placebo (1:1).

Primary and co-primary efficacy endpoints are cognitive and functional cognitive scales: PD-CRS and PD-CFRS. Secondary efficacy endpoints include: cognitive tests evaluating attention, executive functions, language, memory and visuospatial domain; mood, anxiety, and apathy scales; questionnaires to evaluate quality of life; and subjective impression scales. Serum Neurofilament light chain, genetic screening of GBA, ApoE and MAPT, and Magnetic Resonance Imaging will be performed in a subset of these patients.

The study will be conducted in 20 different centers around Spain. The Movement Disorders Unit of the Neurology Department at Sant Pau Hospital (Barcelona, Spain) will be the coordinating center.

Study Overview

• Status: Not yet recruiting
• Conditions: Parkinson Disease; Mild Cognitive Impairment
• Intervention / Treatment: Drug: Placebo; Drug: Donepezil Hydrochloride

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 50-80
• PD diagnosis according to MDS criteria
• Hoehn and Yahr stage I-III
• Persistent subjective cognitive complaints for at least 6 months
• MDS PD-MCI Level I and Level II criteria
• Persistent PD-MCI for at least 3 months
• Stable dopaminergic treatment for at least 1 month

Exclusion Criteria:

• PD dementia criteria
• Severe motor complications
• DBS or any brain condition that may be contributing to cognitive impairment
• Active psychosis, major hallucinations, HADS ≥11, active impulse control disorder, or other active severe behavioral disorders.
• Treatment under anticholinergics, cholinergic enhancers, or neuroleptics.
• History of symptomatic arterial hypotension.
• Hypersensitivity or intolerance to donepezil or any of the excipients
• Pregnancy
• Unstable medical or surgical condition
• Any other significant observation that, in the investigator's opinion, would contraindicate participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo
Experimental: Donepezil	Drug: Donepezil Hydrochloride; Donepezil 10mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parkinson's Disease-Cognitive Rating Scale (PD-CRS)	Global cognition	12 months
Parkinson's Disease-Cognitive Functional Rating Scale (PD-CFRS)	Cognitive functional performance	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trail Making Test A (TMT-A)	Attention	12 months
TMT-B	Executive functions	12 months
Boston Naming Test	Language	12 months
Free and cued selective reminding test	Memory	12 months
Rey-Osterrieth complex figure test (ROCF)	Visuospatial	12 months
Hospital Anxiety and Depression Scale	Depression and Anxiety	12 months
Starkstein Apathy scale	Apathy	12 months
Neuropsychiatric Inventory	Hallucinations	12 months
Schwab & England scale	Quality of life	12 months
Clinical Global Impressions-Severity of illness	Subjective clinical change	12 months
CGI-Global improvement	Subjective clinical change	12 months
Patient Global Impression of Change	Subjective clinical change	12 months
8-item Parkinson's Disease Questionnaire	Quality of life	12 months
Judgment of Line Orientation	Visuspatial	12 months
recall of ROCF	Memory	12 months
Category fluency	Language	12 months
Phonemic Fluency	Executive functions	12 months
direct Digit Span	Attention	12 months

Collaborators and Investigators

• Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: January 11, 2023
• First Submitted That Met QC Criteria: January 31, 2023
• First Posted (Actual): February 2, 2023

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Donepezil; Parkinson's Disease-Mild Cognitive Impairment (PD-MCI); Randomized Clinical Trial (RCT)
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Cognition Disorders; Parkinson Disease; Cognitive Dysfunction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: IIBSP-DON-2022-43

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