Antiplatelet Therapy and Endothelial-stabilizing Agents in Cerebral Small Vessel Diseases

Recruiting

• Conditions: Stroke, Ischemic; Small Vessel Cerebrovascular Disease; White Matter Hyperintensity
• Interventions: Drug: Clopidogrel; Drug: Aspirin; Drug: Cilostazol + Isosorbide Mononitrate

• Registration Number: NCT06715007
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

Brief Summary

Cerebral small vessel disease (cSVD) is a common accompaniment of aging. Recent small subcortical (or lacunar) infarcts (i.e. symptomatic cSVD) and white matter hyperintensities are typical cSVD lesions on neuroimaging. cSVD causes about a quarter of ischaemic strokes and related with cognitive dysfunction. However, few studies are available so far to especially explore the treatment of cSVD. Endothelial dysfunction plays an important part in cSVD. Cilostazol and isosorbide mononitrate have endothelial protective function. We designed this prospective cohort study in China, aiming to evaluate the effect of different antiplatelet agents (e.g. Cilostazol) on cSVD and retina in patients with cSVD (recent small subcortical infarcts or WMH, respectively).

Detailed Description

Cerebral small vessel disease (cSVD) is a common accompaniment of aging. It refers to a group of pathological processes with various etiologies that affect the small arteries, arterioles, venules, and capillaries of the brain. On neuroimaging, notably on magnetic resonance imaging (MRI), SVD has several visible signs, including recent small subcortical infarcts (i.e symptomatic cSVD in our study), lacunes of presumed vascular origin; white matter hyperintensities (WMH), perivascular spaces, cerebral microbleeds, cerebral microinfarcts and brain atrophy. SVD causes about a quarter of ischaemic strokes, is the main cause of vascular dementia, often occurs with Alzheimer's disease, contributing to about 50% of dementias worldwide. Although previous studies recommend BP control and antiplatelet therapy in symptomatic cSVD, secondary prevention strategies are mostly inferred from studies of ischemic stroke in general, the majority of which did not specifically investigate patients with symptomatic cSVD. In addition, long term dual antiplatelet therapy using clopidogrel and aspirin was shown to increase the risk of hemorrhage stroke in symptomatic cSVD, without any decrease in recurrent ischemic stroke.

Endothelial dysfunction plays an important part in cSVD. In addition to mild antiplatelet effects through the increase of cyclic adenosine monophosphate (cAMP), the phosphodiesterase (PDE) 3' inhibitor cilostazol is shown to be endothelial protective by several pathways, such as activation of endothelial nitric oxide (NO) synthase (NOS), regulation of endothelin-1. Isosorbide mononitrate (ISMN) is a NO donor, by augmenting the NO-cyclic guanosinemonophosphate phosphodiesterase-inhibitor pathway. Recent trial showed that the combined use of ISMN plus cilostazol was well tolerated and safe, and may reduce recurrent stroke and cognitive impairment after lacunar stroke.

Brain and retina possess numerous anatomical and functional similarities. Retinal capillary microvessels revealed by optical coherence tomography angiography (OCTA) have been found to be related to brain microvessels, reflecting the burden of cSVD. Retinal perfusion is also linked with cognitive function.

This cohort study will prospectively evaluate the effect of different antiplatelet agents on cSVD and retina in patients with cSVD (recent small subcortical infarcts or WMH, respectively).

Study Timeline

• Study First Submitted: 2023-11-27
• Study First Submitted QC: 2024-12-03
• Study First Posted: 2024-12-04
• Study Start: 2024-12-20
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-28
• Primary Completion: 2025-12-20
• Study Completion: 2026-01-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with Whiter matter changes	Cilostazol + Isosorbide Mononitrate	White matter hyperintensities with a 2-3 grading on Fazekas scale will be recruited. Patient in this group will receive antiplatelet treatment (e.g. Aspirin, Clopidogrel, or Cilostazol),
Patients with recent small subcortical infarct	Clopidogrel	Patient in this group will receive antiplatelet treatment (e.g. Aspirin, Clopidogrel, or Cilostazol),
Patients with recent small subcortical infarct	Aspirin	Patient in this group will receive antiplatelet treatment (e.g. Aspirin, Clopidogrel, or Cilostazol),
Patients with recent small subcortical infarct	Cilostazol + Isosorbide Mononitrate	Patient in this group will receive antiplatelet treatment (e.g. Aspirin, Clopidogrel, or Cilostazol),
Patients with Whiter matter changes	Clopidogrel	White matter hyperintensities with a 2-3 grading on Fazekas scale will be recruited. Patient in this group will receive antiplatelet treatment (e.g. Aspirin, Clopidogrel, or Cilostazol),
Patients with Whiter matter changes	Aspirin	White matter hyperintensities with a 2-3 grading on Fazekas scale will be recruited. Patient in this group will receive antiplatelet treatment (e.g. Aspirin, Clopidogrel, or Cilostazol),

Primary Outcome Measures

Name	Time	Method
the impact of different antiplatelet agents on retinal vasculature.	6 months follow up	retinal vasculature will be assessed by optical coherence tomography and optical coherence tomography angiography.

Secondary Outcome Measures

Name	Time	Method
Neurological function	Neurological function will be assessed at baseline, 1 week, 3 months and 6-month after recruitment.	Neurological function will be assessed by NIHSS (National institute of health stroke scale)
Brain MRI (magnetic resonance imaging)	Brain MR will be performed at baseline and at 6 months after recruitment	Brain MRI to evaluate whiter matter hyperintensities.
systemic or intracranial bleeding	systemic or intracranial bleeding will be assessed during 6 month follow-up.
occurrence of ischemic stroke or transient ischemic attack	during 6 month follow-up
Cognitive function	MoCA will be assessed at baseline and at 3 and 6 months after recruitment.	Montreal cognitive assessment (MoCA) will be used.
modified Rankin Scale (mRS) score	modified Rankin Scale (mRS) score will be assessed at baseline and at 3 and 6 months after recruitment.
Barthel index for activities of daily living	Barthel index will be assessed at baseline, 3 and 6 months after recruitment.	Barthel index for activities of daily living is an ordinal scale which measures a person's ablility to complete activities of of daily living.
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	UPDRS score will be evaluated at baseline and 3, 6 months after recruitment.	MDS-UPDRS is scale to evaluate various aspects Parkinson's disease or Parkinsonism including non-motor and motor experiences of daily living and motor complications. Small vessel diseases may cause Parkinsonism, we thus use this scale in our study.

Trial Locations

Locations (1)

the First affiliated hospital of Nanjing Medical University; 🇨🇳 Nanjing, Jiangsu, China