Clinical trial NCT01932203: Efficacy Study of Cilostazol and Aspirin on Cerebral Small Vessel Disease
Official title: A Multicenter, Randomized, Double Blind Study to Compare the Efficacy Between Cilostazol and Aspirin on White Matter Changes by Cerebral Small Vessel Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Cerebral Small Vessel Disease
Keywords: Cerebral small vessel disease
Leukoaraiosis
Magnetic Resonance Imaging
Diffusion Tensor Imaging
Lead sponsor: Inha University Hospital
Sponsor class: OTHER
Collaborators: name: Otsuka Pharmaceutical Development & Commercialization, Inc.
First posted: 2013-08-30
Enrollment: 255
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Volume of white matter changes (WMCs)
timeFrame: baseline, week 104
Secondary outcomes:
measure: Mean diffusivity (MD) and Fraction Anisotropy (FA) on Diffusion Tensor Imaging
timeFrame: baseline and week 104
measure: Number of lacunes
timeFrame: baseline and week 104
measure: number of microbleeds
timeFrame: baseline and week 104
measure: brain volume and cortical thickness
timeFrame: baseline and week 104
measure: Mini-Mental State Examination
timeFrame: baseline, week 52, and week 104
measure: Neurocognitive test
timeFrame: baseline, week 52, and week 104
measure: Clinical Dementia Rating scale-sum of boxes
timeFrame: baseline, week 52, and week 104
measure: King's Health Questionnaire
timeFrame: baseline, week 42, and week 104
measure: Geriatric Depression Scale-Short form
timeFrame: baseline, week 52, and week 104
measure: Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI)
timeFrame: baseline, week 52, and week 104
measure: Bayer Activities of Daily Living
timeFrame: baseline, week 52, and week 104
measure: Barthel Index
timeFrame: baseline, week 52, and week 104
measure: Pyramidal and Extrapyramidal Scale (PEPS)
timeFrame: baseline, week 52, and week 104
measure: Timed UP and Go (TUG) test
timeFrame: basline, week 52, and week 104
measure: Adverse event
timeFrame: baseline, week 4, 16, 28, 40, 52, 64, 76, 88, and 104
Other outcomes:
measure: All ischemic stroke event
timeFrame: week 104
measure: All vascular events
timeFrame: week 104
Locations:
city: Goyang-si
country: Korea, Republic of
facility: Myongji Hospital
state: Gyeonggi-do
city: Goyang-si
country: Korea, Republic of
facility: National Health Insurance Corporation Ilsan Hospital
state: Gyeonggi-do
city: Hwaseong-si
country: Korea, Republic of
facility: Dongtan Sacred Heart Hospital, Hallym University College of Medicine
state: Gyeonggi-do
city: Iksan
country: Korea, Republic of
facility: Wonkwang University Iksan Hospital
state: Jeollabuk-do
city: Anyang
country: Korea, Republic of
facility: Hallym University Medical Center
city: Bucheon
country: Korea, Republic of
facility: Bucheon St.Mary's Hospital
city: Bucheon
country: Korea, Republic of
facility: Soonchunhyang University Bucheon Hospital
city: Daejeon
country: Korea, Republic of
facility: Eulji University School of Medicine
city: Daejeon
country: Korea, Republic of
facility: Konyang University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical
city: Pusan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Pusan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Chungang University Hospital
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Inha University Hospital
name: Seong Hye Choi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kwan J, Hafdi M, Chiang LLW, Myint PK, Wong LS, Quinn TJ. Antithrombotic therapy to prevent cognitive decline in people with small vessel disease on neuroimaging but without dementia. Cochrane Database Syst Rev. 2022 Jul 14;7(7):CD012269. doi: 10.1002/14651858.CD012269.pub2.
citation: Kim BC, Youn YC, Jeong JH, Han HJ, Kim JH, Lee JH, Park KH, Park KW, Kim EJ, Oh MS, Shim Y, Lee JM, Choi YH, Park G, Kim S, Park HY, Yoon B, Yoon SJ, Cho SJ, Park KC, Na DL, Park SA, Choi SH. Cilostazol Versus Aspirin on White Matter Changes in Cerebral Small Vessel Disease: A Randomized Controlled Trial. Stroke. 2022 Mar;53(3):698-709. doi: 10.1161/STROKEAHA.121.035766. Epub 2021 Nov 16.
citation: Han HJ, Kim BC, Youn YC, Jeong JH, Kim JH, Lee JH, Park KH, Park KW, Kim EJ, Oh MS, Shim YS, Park HY, Yoon B, Yoon SJ, Cho SJ, Park KC, Na DL, Park SA, Lee JM, Choi SH. A Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes: Protocol of a Multicenter, Randomized Controlled Trial. Dement Neurocogn Disord. 2019 Dec;18(4):138-148. doi: 10.12779/dnd.2019.18.4.138. Epub 2019 Dec 13.