Stroke, IschemicAthena-cSVDNCT06715007
Antiplatelet Therapy and Endothelial-stabilizing Agents in Cerebral Small Vessel Diseases
An observational study of Stroke, Ischemic and Small Vessel Cerebrovascular Disease, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 79 years
- Conditions the study is for
- Stroke, Ischemic, Small Vessel Cerebrovascular Disease, White Matter Hyperintensity
- What is being tested?
- Clopidogrel, Aspirin and Cilostazol + Isosorbide Mononitrate
- How many people
- 300 participants
- Where
- 1 siteChina
- Study dates
- 20 Dec 2024to 20 Jan 2026
- How long will I take part?
- 6 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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).
- 7. 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.
- 8. No major-risk cardioembolic sources requiring anticoagulation or other specific therapy.
- 9. 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Xinyu Chen contact
China1 site, 1 recruiting
- Recruiting
the First affiliated hospital of Nanjing Medical University
Nanjing, Jiangsu, 210001
Zhaolu Wang, MD, PhD, 18100613663, wangzhaolu123@163.com
About this study
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).
Read the 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).
- Being tested
- Clopidogrel, Aspirin, Cilostazol + Isosorbide Mononitrate
- Keywords
- cerebral small vessel disease, White Matter Hyperintensity, recent small subcortical infarcts, Endothelial dysfunction, cilostazol
- Medical subject headings
- Ischemic Stroke, Cerebral Small Vessel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClopidogrelDrug
Patients will take Clopidogrel
AspirinDrug
Patients will take Rivaroxaban
Cilostazol + Isosorbide MononitrateDrug
Patients will take Cilostazol plus Isosorbide Mononitrate
| Study group | Role | What they receive |
|---|---|---|
| Patients with recent small subcortical infarct | Patient in this group will receive antiplatelet treatment (e.g. Aspirin, Clopidogrel, or Cilostazol), Receives: 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), Receives: Drug: Clopidogrel; Drug: Aspirin; Drug: Cilostazol + Isosorbide Mononitrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
the impact of different antiplatelet agents on retinal vasculature.
retinal vasculature will be assessed by optical coherence tomography and optical coherence tomography angiography.
Measured: 6 months follow up
Secondary outcomes (8)
systemic or intracranial bleeding
Measured: systemic or intracranial bleeding will be assessed during 6 month follow-up.
occurrence of ischemic stroke or transient ischemic attack
Measured: during 6 month follow-up
Neurological function
Neurological function will be assessed by NIHSS (National institute of health stroke scale)
Measured: Neurological function will be assessed at baseline, 1 week, 3 months and 6-month after recruitment.
Brain MRI (magnetic resonance imaging)
Brain MRI to evaluate whiter matter hyperintensities.
Measured: Brain MR will be performed at baseline and at 6 months after recruitment
Cognitive function
Montreal cognitive assessment (MoCA) will be used.
Measured: MoCA will be assessed at baseline and at 3 and 6 months after recruitment.
modified Rankin Scale (mRS) score
Measured: 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 for activities of daily living is an ordinal scale which measures a person's ablility to complete activities of of daily living.
Measured: Barthel index will be assessed at baseline, 3 and 6 months after recruitment.
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
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.
Measured: UPDRS score will be evaluated at baseline and 3, 6 months after recruitment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2024
- Study start20 Dec 2024
- Primary completion20 Dec 2025 (estimated)
- Study completion20 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stroke, IschemicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
- Target duration
- 6 Months
Sponsor and investigators
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wang Zhaolu, The First Affiliated Hospital with Nanjing Medical University
- Investigators
- zhaolu wang, MD, Study director, The First Affiliated Hospital with Nanjing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06715007
- Sponsor's protocol ID
- Athena-cSVD
- Acronym
- Athena-cSVD
- Status last verified
- Mar 2025
- First submitted
- 27 Nov 2023
- Last updated
- 28 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antiplatelet Therapy and Endothelial-stabilizing Agents in Cerebral Small Vessel Diseases
- ClinicalTrials.gov ID
- NCT06715007
- Acronym / sponsor ID
- Athena-cSVD / Athena-cSVD
- Keywords
- cerebral small vessel disease, White Matter Hyperintensity, recent small subcortical infarcts, Endothelial dysfunction, cilostazol
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Study start
- 20 Dec 2024 (actual)
- Primary completion
- 20 Dec 2025 (estimated)
- Study completion
- 20 Jan 2026 (estimated)
- First posted
- 4 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 6 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with recent small subcortical infarct | – | Drug: Clopidogrel, Drug: Aspirin, Drug: Cilostazol + Isosorbide MononitratePatient in this group will receive antiplatelet treatment (e.g. Aspirin, Clopidogrel, or Cilostazol), |
| Patients with Whiter matter changes | – | Drug: Clopidogrel, Drug: Aspirin, Drug: Cilostazol + Isosorbide MononitrateWhite 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), |
Who may qualify
- Ages
- 30 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClopidogrelPatients will take Clopidogrel | Drug | Patients with Whiter matter changes, Patients with recent small subcortical infarct |
| AspirinPatients will take Rivaroxaban | Drug | Patients with Whiter matter changes, Patients with recent small subcortical infarct |
| Cilostazol + Isosorbide MononitratePatients will take Cilostazol plus Isosorbide Mononitrate | Drug | Patients with Whiter matter changes, Patients with recent small subcortical infarct |
Primary outcome
the impact of different antiplatelet agents on retinal vasculature.
Time frame: 6 months follow up
retinal vasculature will be assessed by optical coherence tomography and optical coherence tomography angiography.
8 secondary outcomes
systemic or intracranial bleeding
Time frame: systemic or intracranial bleeding will be assessed during 6 month follow-up.
occurrence of ischemic stroke or transient ischemic attack
Time frame: during 6 month follow-up
Neurological function
Time frame: Neurological function will be assessed at baseline, 1 week, 3 months and 6-month after recruitment.
Brain MRI (magnetic resonance imaging)
Time frame: Brain MR will be performed at baseline and at 6 months after recruitment
Cognitive function
Time frame: MoCA will be assessed at baseline and at 3 and 6 months after recruitment.
modified Rankin Scale (mRS) score
Time frame: 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
Time frame: Barthel index will be assessed at baseline, 3 and 6 months after recruitment.
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
Time frame: UPDRS score will be evaluated at baseline and 3, 6 months after recruitment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Xinyu Chen contact
zhaolu wang, MD study director
The First Affiliated Hospital with Nanjing Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Stroke, Ischemic and Small Vessel Cerebrovascular Disease, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhaolu Wang, MD (+86 18100613663, wangzhaolu123@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the impact of different antiplatelet agents on retinal vasculature. (time frame: 6 months follow up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2025.