Cilostazol Augmentation Study in Dementia

Phase 4

Completed

Conditions: Alzheimer's Dementia

Interventions: Drug: Cilostazol
Drug: Placebo

Registration Number: NCT01409564

Lead Sponsor: Seoul National University Hospital

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 46

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cilostazol	Cilostazol	Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation.
Placebo	Placebo	Placebo group means dementia patients group receiving donepezil with placebo.

Primary Outcome Measures

Name	Time	Method
Regionally Averaged Cerebral Glucose Uptake Changes Measured by FDG PET Uptake With Voxel-based Method	Baseline, 24-week	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.

Secondary Outcome Measures

Name	Time	Method
Mini-Mental State Examination (MMSE) in the Korean Version of the CERAD Assessment Packet)	Baseline, 12-month, 24-month	Basic cognitive functions are checked. (0-30) The score is better when higher.
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog)	Baseline, 12-week, 24-week	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. 1. Word-recall test (0-10) 2. Commands (0-5) 3. Constructional praxis (0-5) 4. Naming Objects/ Fingers (0-5) 5. Ideational Praxis (0-5) 6. Orientation (0-8) 7. Word Recognition (0-12) 8. Remembering Test Instructions (0-5) 9. Spoken Language Ability (0-5) 10. Word Finding Difficulty (0-5) 11. Comprehension (0-5)
Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)	Baseline, 12-month, 24-month	Measured by professionally trained clinicians. Higher score indicates more severe AD symptoms. Score Scale: 0-18 (min-MAX)
Activities of Daily Living (ADCS-ADL)	Baseline, 12-month, 24-month	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)
Fazekas Scale	Baseline	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