Effect of Donepezil on Cognition in Parkinson's Disease With Mild Cognitive Impairment (PD-MCI)

Sponsor

Yonsei University (Other)

Overall Status

Unknown status

CT.gov ID

NCT02450786

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

There have been growing interest in identifying Parkinson's disease (PD) patients with mild cognitive impairment (MCI) which is susceptible to progress to PD dementia(PDD). PD-MCI is known to significantly correlates with low cerebrospinal beta-amyloid 1-42 and 1-40 levels, in which suggest the existence of something common with Alzheimer's dementia. PDD have showed more cholinergic deficits than Alzheimer's dementia and responds to donepezil. The investigators assume that PD-MCI patients also have cholinergic deficits. Donepezil improves cognition, and seems to be well tolerated and not to worsen parkinsonism in patients with cognitive impairment. Donepezil produced similar improvements in cognition and behaviour in DLB and PDD. This supports the hypothesis that the two disorders are closely related clinically and neurobiologically. Larger scale, placebo controlled clinical trials are needed to provide an evidence base to guide the clinical use of cholinesterase inhibitors in Lewy body disease.

It is believed that earlier intervention, later appearance of dementia should be needed to lower the socioeconomic costs and to improve the quality of life on patients and caregivers. The investigators anticipate that donepezil may delay the development of dementia in patients with PD-MCI.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: Donepezil	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Study Start Date :

Jun 1, 2015

Anticipated Primary Completion Date :

Aug 1, 2019

Anticipated Study Completion Date :

Aug 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Donepezil group Donepezil is started in 5mg for 8 weeks followed by dose escalation to 10mg and then maintained for 40 weeks. Participants who are not tolerable to dose of 10mg due to any issues of adverse effects would be maintained with donepezil 5mg exclusively in remained period.	Drug: Donepezil Donepezil is started in patients with Parkinson's disease mild cognitive impairment with 5mg for 8 weeks followed by dose up to 10mg and then maintained for 40 weeks. Participants who are not tolerable to dose of 10mg due to any issues of adverse effects would be maintained with donepezil 5mg exclusively in remained period.
No Intervention: control group No administration of any therapeutic medications for dementia including cholinesterase inhibitor or NMDA receptor blocking agents. Standard treatment protocol of Parkinson's disease with mild cognitive impairment would be fulfilled including dopaminergic or nondopaminergic medications as well as nootropic drugs.

Arm

Intervention/Treatment

Experimental: Donepezil group

Donepezil is started in 5mg for 8 weeks followed by dose escalation to 10mg and then maintained for 40 weeks. Participants who are not tolerable to dose of 10mg due to any issues of adverse effects would be maintained with donepezil 5mg exclusively in remained period.

Drug: Donepezil

Donepezil is started in patients with Parkinson's disease mild cognitive impairment with 5mg for 8 weeks followed by dose up to 10mg and then maintained for 40 weeks. Participants who are not tolerable to dose of 10mg due to any issues of adverse effects would be maintained with donepezil 5mg exclusively in remained period.

No Intervention: control group

No administration of any therapeutic medications for dementia including cholinesterase inhibitor or NMDA receptor blocking agents. Standard treatment protocol of Parkinson's disease with mild cognitive impairment would be fulfilled including dopaminergic or nondopaminergic medications as well as nootropic drugs.

Outcome Measures

Primary Outcome Measures

Rate of cognitive decline [at 48wks]
Korean Version of Mini-Mental State Exam

Secondary Outcome Measures

changes of cognitive decline [baseline, 24 wks, 48 wks, 72 wks]
changes of Parkinson's disease motor scale [baseline, 24 wks, 48 wks, 72wks]
UPDRS part I-IV
Brain structure (cortical thickness and subcortical volume/shape) and Default mode network [48wks]
Conventional and functional brian MRI
brain functional connectivity [48wks]
digital electroencephalography
Comprehensive neuropsychological test [48wks]
Seoul Neuropsychological Screening Battery (SNSB)

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age more than 40 years old
Clinical diagnosis of PD established by Queen Square Brain Bank Criteria
Stable dose of levodopa at least 3 months before the study enrollment
Diagnosis of MCI in PD according to the Movement Disorder Society (MDS) task force guideline

Exclusion Criteria:

Diagnosis of Dementia
Hypersensitivity to piperidine derivatives
Concomitant anticholinergics and cholinergic agents
Severe cardiac arrhythmia: Sick sinus syndrome, complete AV block, Uncontrolled arrhythmia, history of ventricular fibrillation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Severance Hospital	Seoul		Korea, Republic of	120-752

Sponsors and Collaborators

Yonsei University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Yonsei University

ClinicalTrials.gov Identifier:

NCT02450786

Other Study ID Numbers:

4-2014-1089

First Posted:

May 21, 2015

Last Update Posted:

Jan 29, 2019

Last Verified:

Jan 1, 2019

Additional relevant MeSH terms:

Parkinson Disease

Donepezil

Study Results

No Results Posted as of Jan 29, 2019