Efficacy Study of Cilostazol and Aspirin on Cerebral Small Vessel Disease

Study Overview
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Brief Summary
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There may be a difference in efficacy of cilostazol and aspirin on progression of white matter changes in cerebral small vessel disease.

Detailed Description
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The primary objective of this study is to compare the efficacy of aspirin and cilostazol on volume of white matter changes in cerebral small vessel disease. The secondary objectives are to compare the impact of aspirin and cilostazol on DTI parameters, lacune, microbleeds, brain atrophy, cognition, depression, neurologic signs, gait, urination, and activities of daily living. We also investigate risk factors associated with progression of cerebral small vessel disease.

Official Title
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A Multicenter, Randomized, Double Blind Study to Compare the Efficacy Between Cilostazol and Aspirin on White Matter Changes by Cerebral Small Vessel Disease

Conditions
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Cerebral Small Vessel Disease

Intervention / Treatment
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* Drug: aspirin
* Drug: cilostazol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 50 to 85 years of age He/She can walk to the hospital (walker or cane is permissible). Cerebral small vessel disease is observed on brain MRI. 1) presence of one or more lacunar infarction and 2) moderate or severe confluent leukoaraiosis (defined as grade 2 or 3 on a modified Fazekas scale): periventricular WMCs with cap or rims lager than 5mm and deep subcortical WMCs >10 mm in maximum diameter written informed consent Exclusion Criteria: Any patient with contraindication of antiplatelets Any patient with cardioembolic source Carotid bruit or large cerebral artery stenosis >50% Cortical infarction or subcortical infarction lager than 1.5 cm bleeding tendency chronic liver disease (AST or ALT >100 IL/L) chronic renal disease (Creatinine >3.0mg/dL) active gastrointestinal ulcer any patients with any severe or unstable medical disease that may prevent them from completing study requirements (i.e., unstable or severe asthma) Anemia (Hb <10g/dL) or thrombocytopenia Cardiac pacemaker or contraindication to MRI Pregnancy or breast-feeding drug or alcohol addiction Any other white matte disease (i.e., Multiple sclerosis, sarcoidosis, or brain irradiation, etc) or brain tumor Parkinson's disease, Alzheimer's disease or any other neurodegenerative disease any hearing or visual impairment that can disturb the efficient evaluation of the patient recent cerebral infarction with 3 months

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: aspirin<br>aspirin 100mg by mouth once a day for 104 weeks | Drug: aspirin<br>* 100mg once a day<br>|
| Experimental: Cilostazol<br>Pletaal SR 200mg by mouth once a day for 104 weeks | Drug: cilostazol<br>* 200mg once a day<br>* Other names: Pletaal SR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume of white matter changes (WMCs) | Measure change of WMC on brain MRI | baseline, week 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean diffusivity (MD) and Fraction Anisotropy (FA) on Diffusion Tensor Imaging | High MD and low FA means tissue damage. | baseline and week 104 | 
| Number of lacunes | High number means tissue damage. | baseline and week 104 | 
| number of microbleeds | High number means tissue damage. | baseline and week 104 | 
| brain volume and cortical thickness | Low score means tissue damage. | baseline and week 104 | 
| Mini-Mental State Examination | Measure global cognition. Score range is 0-30. Higher score means good cognition. | baseline, week 52, and week 104 | 
| Neurocognitive test | Seoul Verbal Learning Test, Boston Naming test-short form, ROCF copy, animal fluency, phonemic fluency, Stroop test, Digit-symbol test, Trail making test | baseline, week 52, and week 104 | 
| Clinical Dementia Rating scale-sum of boxes | Measure global cognition. Score range is 0-18. Higher score means good cognition. | baseline, week 52, and week 104 | 
| King's Health Questionnaire | Measure voiding function. Higher score means bad function. | baseline, week 42, and week 104 | 
| Geriatric Depression Scale-Short form | Measure depression. Score range is 0-15. Higher score means depression. | baseline, week 52, and week 104 | 
| Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI) | Measure abnormal behavior. Score range is 0-144. Higher score means severe abnormal behavior. | baseline, week 52, and week 104 | 
| Bayer Activities of Daily Living | Measure instrumental activities of daily living (ADL). Score range is 1-10. Higher score means bad ADL. | baseline, week 52, and week 104 | 
| Barthel Index | Measure physical ADL. Score range is 0-20. Higher score means good physical ADL. | baseline, week 52, and week 104 | 
| Pyramidal and Extrapyramidal Scale (PEPS) | Measure neurologic signs. Score range is 0-60. Higher score means many abnormal neurologic signs. | baseline, week 52, and week 104 | 
| Timed UP and Go (TUG) test | Measure gait. Higher score means bad gait. | basline, week 52, and week 104 | 
| Adverse event | measure any adverse events | baseline, week 4, 16, 28, 40, 52, 64, 76, 88, and 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebral small vessel disease, Leukoaraiosis, Magnetic Resonance Imaging, Diffusion Tensor Imaging