Cilostazol Augmentation Study in Dementia

Alzheimer's Dementia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01409564
• Other study ID #: 06-2009-145
• Status: Completed
• Phase: Phase 4
• First received: August 3, 2011
• Last updated: April 14, 2014
• Start date: May 2010
• Est. completion date: July 2013

Study information

• Verified date: April 2014
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: July 2013
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

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 (? patients with bleeding tendency ? patients with congestive heart failure ? patients who have a medical history of hypersensitivity to this medicine or constituent of this medicine ? 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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Dementia
• Dementia

Intervention

Drug:
• Cilostazol
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
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.

Locations

Country	Name	City	State
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Korea OIAA

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No