Cilostazol Augmentation Study in Dementia

Study Overview
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Brief Summary
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The purpose of this study is to examine the effects of cilostazol augmentation in mild to moderate Alzheimer disease patients with subcortical white matter hyperintensities (WMHI) treated by donepezil. Dementia is the most disabling disease in the old age. The prevalence of dementia is 5-10% of the elders. AchEIs (donepezil, galantamine, rivastigmine) are used to treat mild to moderate dementia, but these drugs only relate to symptomatic improvement and the response rates are less than 30%. Cilostazol is a cyclic adenosine monophosphate phosphodiesterase 3 inhibitor (PDE3I) and used as antiplatelet agent in subcortical vascular disease (WMHI). And it upregulates phosphorylation of cyclic adenosine monophosphate-pathway response element binding protein (CREB) which plays a crucial role in memory enhancement and synaptic plasticity related to neurodegeneration prevention. The investigators will try cilostazol augmentation in dementia patients with WMHI receiving donepezil to see the addictive effects of cilostazol using cognitive tasks and PET imaging.

Official Title
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Cilostazol Augmentation Study In Dementia (CASID): A Randomized, Placebo-controlled Pilot Study to Compare the Efficacy Between Donepezil Monotherapy and Cilostazol Augmentation Therapy in Alzheimer's Disease Patients With Subcortical White Matter Hyperintensities

Conditions
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Alzheimer's Dementia

Intervention / Treatment
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* Drug: Cilostazol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men/women over sixty years old Patients with slight and moderate dementia (MMSE score is over 10 under 26.) Patients with probable Alzheimer's disease according to the standard of NINCDS-ADRDA Patients accompanied with WMHI on Brain MRI (Fazeka's scale 1 3) Exclusion Criteria: Those who do not agree to the test in a written form Patients who accompany other diseases except cerebral atrophy or change of subcortical white matter due to Alzheimer's disease on brain MRI Patients who should not use Cilostazol (① patients with bleeding tendency ② patients with congestive heart failure ③ patients who have a medical history of hypersensitivity to this medicine or constituent of this medicine ④ those who use anticoagulant and clot buster) Patients who suffer from nerve diseases or mental diseases which have influence on cognitive function except Alzheimer's disease (for example, schizophrenia, severe depression, mental retardation and etc.) Patients who are suspected to have a personal history of drug addiction or alcoholism within recent 10 years Patients who have severe problems in eye sight or hearing so that it is impossible to conduct the test smoothly Patients who the researchers think are inappropriate for taking part in the test

Ages Eligible for Study
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Minimum Age: 60 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cilostazol<br>Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation. | Drug: Cilostazol<br>* Cilostazol 100mg bid per day will be administered orally and the period is total 24 weeks. The first week is a period for increasing the quantity, and during this period, cilostazol 50mg bid per day will be administered orally.<br>|
| Placebo Comparator: Placebo<br>Placebo group means dementia patients group receiving donepezil with placebo. | Drug: Placebo<br>* Placebo with similar shape and color to cilostazol 100mg bid per day will be administered orally and the period is total 24 weeks. The first week is a period for increasing the quantity, and during this period, placebo 50mg bid per day will be administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regionally Averaged Cerebral Glucose Uptake Changes Measured by FDG PET Uptake With Voxel-based Method | Regional cerebral glucose uptake level was measured as the ratio value of FDG uptake of the each unit level to the global mean uptake value. | Baseline, 24-week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) | The ADAS-Cog score is measured by the number of questions answered incorrectly, therefore the higher is the worse. Score Scale: 0-75 (min-MAX) Each subcategory scores are summed. Word-recall test (0-10) Commands (0-5) Constructional praxis (0-5) Naming Objects/ Fingers (0-5) Ideational Praxis (0-5) Orientation (0-8) Word Recognition (0-12) Remembering Test Instructions (0-5) Spoken Language Ability (0-5) Word Finding Difficulty (0-5) Comprehension (0-5) | Baseline, 12-week, 24-week | 
| Mini-Mental State Examination (MMSE) in the Korean Version of the CERAD Assessment Packet) | Basic cognitive functions are checked. (0-30) The score is better when higher. | Baseline, 12-month, 24-month | 
| Activities of Daily Living (ADCS-ADL) | The caregiver answered to the questions given to measure the cognitive function level of the patients in daily living. Lower scores indicate greater severity. 23 questions Score Scale: 0-78 (min-MAX) | Baseline, 12-month, 24-month | 
| Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) | Measured by professionally trained clinicians. Higher score indicates more severe AD symptoms. Score Scale: 0-18 (min-MAX) | Baseline, 12-month, 24-month | 
| Fazekas Scale | Level of severity of white matter lesions in AD patients who can be legitimately administered with cilostazol. Measured by professionally trained clinicians. The higher score indicates more severe white matter lesion. Max-min: 0-3 | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's dementia, Cilostazol