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

Study Overview
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Brief Summary
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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.

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

Conditions
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Parkinson Disease, Mild Cognitive Impairment

Intervention / Treatment
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* Drug: Donepezil Hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donepezil<br> | Drug: Donepezil Hydrochloride<br>* Donepezil 10mg once daily<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's Disease-Mild Cognitive Impairment (PD-MCI), Donepezil, Randomized Clinical Trial (RCT)