Cilostazol Augmentation Study in Dementia
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||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|
- Regionally Averaged Cerebral Glucose Uptake Changes Measured by FDG PET Uptake With Voxel-based Method [ Time Frame: Baseline, 24-week ] [ Designated as safety issue: No ]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.
- Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) [ Time Frame: Baseline, 12-week, 24-week ] [ Designated as safety issue: No ]
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)
- Mini-Mental State Examination (MMSE) in the Korean Version of the CERAD Assessment Packet) [ Time Frame: Baseline, 12-month, 24-month ] [ Designated as safety issue: No ]Basic cognitive functions are checked. (0-30) The score is better when higher.
- Activities of Daily Living (ADCS-ADL) [ Time Frame: Baseline, 12-month, 24-month ] [ Designated as safety issue: No ]
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)
- Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) [ Time Frame: Baseline, 12-month, 24-month ] [ Designated as safety issue: No ]
Measured by professionally trained clinicians. Higher score indicates more severe AD symptoms.
Score Scale: 0-18 (min-MAX)
- Fazekas Scale [ Time Frame: Baseline ] [ Designated as safety issue: No ]
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
|Study Start Date:||May 2010|
|Study Completion Date:||July 2013|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation.
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.
Placebo Comparator: Placebo
Placebo group means dementia patients group receiving donepezil with placebo.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01409564
|Korea, Republic of|
|SMG-SNU Boramae Medical Center|
|Seoul, Korea, Republic of, 156-707|
|Principal Investigator:||Jung-Seok Choi, MD, PhD||SMG-SNU Boramae Medical Center, Seoul, Republic of Korea|