Efficacy and Safety of Donepezil Hydrochloride in Mild Cognitive Impairment Associated with Parkinson's Disease: A Randomized, Double-Blind, Placebo-Controlled Trial
- Trial ID
- 2024-510959-35-00
- Protocol
- IIBPS-DON-2022-43
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this multicenter, randomized, double-blind, and placebo-controlled clinical trial is to assess the **safety** and **efficacy** of donepezil on cognitive performance over a 12-month period in patients with mild cognitive impairment associated with **Parkinson's disease**. This is clinically relevant as it aims to determine the potential benefits of donepezil, a drug primarily used for Alzheimer's disease, in improving cognitive function in Parkinson's disease, which could lead to enhanced management strategies for cognitive symptoms in these patients.
Secondary objectives include:
- Evaluating the effects of donepezil on various cognitive tests and domains by analyzing changes in specific cognitive assessments from baseline to 12 months.
- Assessing the impact of donepezil on anxiety, depression, apathy, psychosis, sleep, and autonomic dysfunction through changes in relevant scales over the same period.
- Examining the influence of donepezil on quality of life by monitoring changes in the Schwab & England Scale and the Parkinson's Disease Questionnaire.
- Evaluating the effects on the severity and overall clinical status of the patient using the Clinical Global Impressions scales.
- Assessing changes in subjective cognitive status through the Patient Global Impression of Change scale.
Participants
The clinical trial involves participants diagnosed with **Parkinson's disease**, specifically targeting those with Parkinson's disease-related mild cognitive impairment (PD-MCI). The study population includes both male and female subjects, aged between 50 and 80 years. Participants are required to have a diagnosis based on MDS criteria, with neuroimaging results compatible with Parkinson's disease, and must be within Hoehn and Yahr stages I-III. The trial does not include a vulnerable population. Participants must have persistent subjective cognitive complaints for at least six months prior to screening and a stable dopaminergic treatment for four weeks before screening. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is a **multicenter**, **randomized**, **double-blind**, and **placebo-controlled** study designed to evaluate the efficacy and safety of **donepezil** in patients with mild cognitive impairment associated with **Parkinson's disease**. The trial will span a duration of 12 months, with the primary objective of assessing the impact of donepezil on cognitive performance. Participants will be randomly assigned to receive either donepezil or a placebo, with neither the participants nor the investigators aware of the group assignments, ensuring the double-blind nature of the study.
The trial will commence with an inclusion (screening) visit, where eligibility will be determined based on criteria such as age between 50 and 80 years, a diagnosis of Parkinson's disease according to MDS criteria, and persistent subjective cognitive complaints. Neuroimaging compatible with Parkinson's disease and a stable dopaminergic treatment in the four weeks prior to screening are also required. Following successful screening, participants will be enrolled and begin the treatment phase.
Throughout the trial, participants will attend regular follow-up visits to monitor safety and efficacy outcomes. These visits will include assessments using the Parkinson's Disease-Cognitive Rating Scale (PD-CRS) and the Parkinson's Disease-Cognitive Functional Rating Scale (PD-CFRS) as primary endpoints. Secondary endpoints will involve a range of neuropsychological tests and scales, such as the Trail Making Test, Boston Nomination Test, and the Hospital Anxiety and Depression Scale, among others. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the overall impact of the treatment.
Participant involvement is expected to last for the entire 12-month period unless conditions arise that necessitate early termination. Such conditions may include adverse events, withdrawal of consent, or any situation where continued participation is deemed not in the best interest of the participant. The trial is categorized as a Phase 4 study, focusing on the safety and efficacy of donepezil in this specific patient population.
Treatment
The clinical trial involves the administration of **donepezil hydrochloride**, marketed under the name ARICEPT, as the experimental medication. ARICEPT is provided in the form of **film-coated tablets**, each containing 10 mg of the active substance. The route of administration is **oral**, and the maximum daily dose is set at 15 mg. The treatment period extends up to 12 months. Donepezil hydrochloride is a chemical compound, and its use in this trial is to evaluate its efficacy and safety in improving cognitive performance in patients with mild cognitive impairment associated with Parkinson's disease. The pharmaceutical product is manufactured by EISAI GMBH and is authorized for use in Spain.
The study is designed as a multicenter, randomized, double-blind, and placebo-controlled trial. Participants will be randomly assigned to receive either the experimental treatment, donepezil hydrochloride, or a **placebo**. The placebo is used as a comparator to assess the true efficacy of the experimental medication. Both the experimental and placebo treatments will be administered in a similar manner to maintain the integrity of the double-blind design. Compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.
Efficacy
The efficacy of donepezil in the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoints include the Parkinson's Disease-Cognitive Rating Scale (PD-CRS) and the Parkinson's Disease-Cognitive Functional Rating Scale (PD-CFRS). These scales are designed to evaluate cognitive performance in patients with mild cognitive impairment associated with Parkinson's disease. Secondary endpoints encompass a range of neuropsychological and functional assessments, including the Trail Making Test A (TMT-A), Trail Making Test B (TMT-B), Digit Span direct (DSd), Phonemic fluency, Boston Nomination Test reduced (BNTr), Semantic fluency, Free and Cued Selective Reminding Test (FCSRT), Rey-Osterrieth Complex Figure (ROCF) and its recall (rROCF), Judgement of Line Orientation (JLO), Hospital Anxiety and Depression Scale (HADS), Starkstein Apathy Scale (AS), Neuropsychiatric Inventory (NPI), MDS UPDRS-I and -II, Schwab & England scale (S&E), 8-item Parkinson’s Disease Questionnaire (PDQ-8), Clinical Global Impressions (CGI-S and CGI-I), and Patients Global Impression of Change (PGIC).
The trial is structured as a multicenter, randomized, double-blind, and placebo-controlled study, with efficacy assessments conducted over a 12-month period. The primary and secondary endpoints will be measured at various timepoints throughout the study to monitor changes in cognitive function and other related parameters. The use of validated scales and tests ensures the reliability and accuracy of the data collected. The trial aims to provide comprehensive insights into the cognitive benefits of donepezil in patients with Parkinson's disease-related mild cognitive impairment.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age between 50 and 80 years (inclusive).
- Diagnosis of Parkinson's disease based on MDS criteria
- Neuroimaging compatible with Parkinson's disease
- Hoehn and Yahr stage (H&Y) I-III (inclusive).
- Persistent subjective cognitive complaints in the 6 months prior to screening.
- Diagnosis of Parkinson's disease-related mild cognitive impairment (PD-MCI) according to MDS PD-MCI criteria: Level I: MoCA ≤24 and ≥20(46) and Level II: 2/10 neuropsychological tests altered with a cutoff of 1.5 Standard Deviations(47,48).
- Duration of PD-MCI for at least 3 months prior to screening.
- Stable dopaminergic treatment in the 4 weeks prior to screening.
Exclusion Criteria
- Criteria for dementia associated with Parkinson's disease
- Severe motor complications (moderate to severe motor fluctuations defined as a score >1 on item 42 of Part IV of the MDS UPDRS; or disabling dyskinesias defined as a score >1 on item 36 of Part IV of the MDS UPDRS).
- History of Deep Brain Stimulation.
- Active psychosis or treatment with antipsychotic medications, major hallucinations, HADS score ≥11, active impulse control disorder, or other severe active behavioral disorders.
- Active treatment with anticholinergics, acetylcholinesterase inhibitors, or other systemic cholinergic enhancers, neuroleptics, potent CYP3A4 or 2D6 inhibitors, enzyme inducers, or drugs prolonging the QTc interval (see section 6.7).
- Hypersensitivity or intolerance to donepezil, piperidine derivatives, lactose, or any of the excipients of the active drug.
- History or impression, at the investigator's discretion, of poor therapeutic compliance.
- Unstable medical or surgical condition, or life expectancy of <1 year.
- Brain condition that may contribute to cognitive decline (history of stroke, brain tumor, neurosurgical intervention, etc.), including the presence of grade III leukoaraiosis on brain neuroimaging.
- Insufficient proficiency in Spanish or the local language, illiteracy, sensory impairments (vision, hearing), legal incapacity, or any other mental, physical, or social condition that impedes giving informed consent or completing assessments adequately.
- History of symptomatic orthostatic hypotension.
- Pregnancy, desire for conception, refusal to use appropriate contraceptives during the study period and up to 6 months after, or lactation (see section 9.6).
- Any significant abnormalities in medical history, examination, vital signs, laboratory tests, or ECG that, at the investigator's discretion, contraindicate participation in the study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Recruiting | 21 Sept 2023 | 120 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ARICEPT 10mg comprimidos recubiertos con película | Test | COMPRIMIDOS RECUBIERTOS CON PELÍCULA | ORAL | 15 | 12 | PRD10257937 |