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

NCT06715007 | Recruiting DMC

• 1 other identifier: Athena-cSVD
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

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).

Conditions

Stroke, Ischemic; Small Vessel Cerebrovascular Disease; White Matter Hyperintensity

Keywords

cerebral small vessel disease; White Matter Hyperintensity; recent small subcortical infarcts; Endothelial dysfunction; cilostazol

Outcome Measures

Primary Outcomes (1)

• the impact of different antiplatelet agents on retinal vasculature.

  retinal vasculature will be assessed by optical coherence tomography and optical coherence tomography angiography.

  6 months follow up

Secondary Outcomes (8)

• 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

• Neurological function

  Neurological function will be assessed at baseline, 1 week, 3 months and 6-month after recruitment.

• Brain MRI (magnetic resonance imaging)

  Brain MR will be performed at baseline and at 6 months after recruitment

• Cognitive function

  MoCA will be assessed at baseline and at 3 and 6 months after recruitment.

Study Arms (2)

Patients with recent small subcortical infarct

Patient in this group will receive antiplatelet treatment (e.g. Aspirin, Clopidogrel, or Cilostazol),

Drug: Clopidogrel; Drug: Aspirin; Drug: Cilostazol + Isosorbide Mononitrate

Patients with Whiter matter changes

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),

Drug: Clopidogrel; Drug: Aspirin; Drug: Cilostazol + Isosorbide Mononitrate

Interventions

Clopidogrel DRUG

Patients will take Clopidogrel

Patients with Whiter matter changes; Patients with recent small subcortical infarct

Aspirin DRUG

Patients will take Rivaroxaban

Patients with Whiter matter changes; Patients with recent small subcortical infarct

Cilostazol + Isosorbide Mononitrate DRUG

Patients will take Cilostazol plus Isosorbide Mononitrate

Patients with Whiter matter changes; Patients with recent small subcortical infarct

Eligibility Criteria

• Age: 30 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with a recent small subcortical infarct that occurred within 3 weeks prior to randomization， or patient with whiter matter hyperintensities with a 2-3 grading on Fazekas scale will be recruited.

You may qualify if:

• Age ≥ 30 years and ≤ 79 years.
• A recent small subcortical infarct that occurred within 3 weeks prior to randomization; or patient with whiter matter hyperintensities with a 2-3 grading on Fazekas scale.
• Absence of signs or symptoms of cortical dysfunction, such as aphasia, apraxia, agnosia, agraphia, homonymous visual field defect.
• Modified Rankin score of ≤ 4.
• In the absence of any other pathology in the parent artery at the site of the origin of the penetrating artery (focal atheroma, parent vessel dissection, vasculitis, vasospasm, and so on).
• \. No ipsilateral cervical carotid stenosis (≥30%) by brain high resolution magnetic resonance imaging (HRMRI) or computed tomography angioplasty (CTA) or (magnetic resonance angioplasty) MRA and cervical artery ultrasound, if qualifying event is hemispheric. No vertebra artery stenosis (≥30%) by brain HRMRI or CTA or MRA and cervical artery ultrasound, if the lesion is in the territory of posterior circulation.
• \. No major-risk cardioembolic sources requiring anticoagulation or other specific therapy.
• \. Patient agrees with follow-up visits and is available by phone. 10. Patient understands the purpose and requirements of the study, can make him/herself understood, and has signed informed consent.

You may not qualify if:

• Intracranial aneurysms that need surgical treatment. Other significant active neurological illness e.g seizures, multiple sclerosis, intracranial tumor (except meningioma) or any intracranial vascular malformation.
• Active cardiac disease (atrial fibrillation, myocardial infarct in last six months, active angina, symptomatic cardiac failure).
• History of any intracranial hemorrhage (parenchymal, subarachnoid, subdural, epidural).
• Known allergy or contraindication to aspirin, clopidogrel, cilostazol, isosorbide mononitrate or statin.
• Active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets \< 100,000, hematocrit \< 30, international normalized ratio (INR) \> 1.5, clotting factor abnormality that increases the risk of bleeding, current alcohol or substance abuse, uncontrolled severe hypertension (systolic pressure \> 180 mm Hg or diastolic pressure \> 115 mm Hg), severe liver impairment (aspartate transaminase \[AST\] or alanine transaminase \[ALT\] \> 3 x normal, cirrhosis), creatine kinase \> 5 times the upper limit of normal (ULN) at final screening, severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) \< 20mL/min/1.73 square meter at final screening.
• Major surgery (including open femoral, aortic, cardiac or carotid surgery) within previous 30 days or planned in the 1 year after enrollment.
• Dementia or psychiatric problem that prevents the patient from relevant evaluation or follow-up reliably.
• Co-morbid conditions that may limit survival to less than 1 year.
• Currently breastfeeding, pregnancy, planning to become pregnant and unwilling to use contraception for the duration of this study
• Unable to tolerate, or contraindication to, MRI.
• Enrollment in another study that would conflict with the current study.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

the First affiliated hospital of Nanjing Medical University

Nanjing, Jiangsu, 210001, China

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood

MeSH Terms

Conditions

Ischemic Stroke; Cerebral Small Vessel Diseases

Interventions

Clopidogrel; Aspirin; Cilostazol; isosorbide-5-mononitrate

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Tetrazoles; Azoles; Quinolines

Study Officials

• zhaolu wang, MD

  The First Affiliated Hospital with Nanjing Medical University

  STUDY DIRECTOR

Central Study Contacts

Zhaolu Wang, MD

CONTACT

+86 18100613663; wangzhaolu123@163.com

Xinyu Chen

CONTACT

njmuchenxinyu@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 27, 2023
• First Posted: December 4, 2024
• Study Start: December 20, 2024
• Primary Completion: December 20, 2025
• Study Completion: January 20, 2026
• Last Updated: March 28, 2025

Record last verified: 2025-03

Locations

CN (1)