Clinical trial NCT01409564: Cilostazol Augmentation Study in Dementia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Alzheimer's Dementia
Keywords: Alzheimer's dementia
Cilostazol
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Korea OIAA
First posted: 2011-08-04
Enrollment: 46
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Regionally Averaged Cerebral Glucose Uptake Changes Measured by FDG PET Uptake With Voxel-based Method
timeFrame: Baseline, 24-week
Secondary outcomes:
measure: Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog)
timeFrame: Baseline, 12-week, 24-week
measure: Mini-Mental State Examination (MMSE) in the Korean Version of the CERAD Assessment Packet)
timeFrame: Baseline, 12-month, 24-month
measure: Activities of Daily Living (ADCS-ADL)
timeFrame: Baseline, 12-month, 24-month
measure: Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)
timeFrame: Baseline, 12-month, 24-month
measure: Fazekas Scale
timeFrame: Baseline
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center
Study officials:
affiliation: SMG-SNU Boramae Medical Center, Seoul, Republic of Korea
name: Jung-Seok Choi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee JY, Lee H, Yoo HB, Choi JS, Jung HY, Yoon EJ, Kim H, Jung YH, Lee HY, Kim YK. Efficacy of Cilostazol Administration in Alzheimer's Disease Patients with White Matter Lesions: A Positron-Emission Tomography Study. Neurotherapeutics. 2019 Apr;16(2):394-403. doi: 10.1007/s13311-018-00708-x.