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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Donepezil | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Donepezil Hydrochloride | Drug | Donepezil 10mg once daily |
| |
| Placebo |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Trail Making Test A (TMT-A) | Attention | 12 months |
| TMT-B | Executive functions | 12 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Drug |
Matching placebo |
|
| 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 |
| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000077265 | Donepezil |
| ID | Term |
|---|---|
| D007189 | Indans |
| D007192 | Indenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |
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