Cerebral Small Vessel DiseasesCIRCLENCT03542734
Cognitive Impairment, Retinopathy, and Cerebrovascular Lesions in the Elderly
An observational study of Cerebral Small Vessel Diseases and Retinopathy, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
The CIRCLE study is a single-center prospective observational study that enrolled individuals with cerebral small vessel disease (SVD), while free of known dementia or stroke (both cerebral infarction and hemorrhage). Read more about this study
- Who is it for?
- Ages 40 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cerebral Small Vessel Diseases, Retinopathy, Cognitive Dysfunction
- What is being tested?
- multimodal magnetic resonance imaging
- How many people
- 1,000 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2010to 30 Jun 2031
- How long will I take part?
- 5 Years
- 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 40 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Residents of certain towns
Who may be able to join
- Adult (≥40y; no upper limit)
- Free of known dementia or stroke (both cerebral infarction and hemorrhage)
Who cannot join
- Any MRI contraindications
- Serious head injury (resulting to loss of consciousness) or received intracranial surgery
- Suffering from cancer
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The second affiliated hospital of Zhejiang University
Hangzhou, 310000
Min Lou, Ph.D, 13958007213, loumingxc@vip.sina.com
About this study
Official title: The Associations of Retinal Microvascular Signs and Brain Imaging Markers With Cognitive Impairment in Patients With Small Vessel Disease
The CIRCLE study is a single-center prospective observational study that enrolled individuals with cerebral small vessel disease (SVD), while free of known dementia or stroke (both cerebral infarction and hemorrhage). The patients will receive neuropsychological testing, retinal digital images and multimodal magnetic resonance imaging (MRI). Blood samples will also be collected. Recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy will be evaluated on both baseline and follow-up brain MRIs. The investigators will explore the predictors of preogression of SVD and cognitive deficits.
Read the detailed description
Cerebral small vessel disease (SVD) is commonly detected in elderly individuals, and patients with stroke or neurodegenerative disease. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. Previous studies indicated that SVD was associated with an increased risk of stroke and stroke recurrence, cognitive deficits, physical disabilities, and mortality. However the pathogenesis of SVD is largely unknown. Little is known about how SVD lesions contribute to neurological or cognitive symptoms, and the association with risk factors. Recent data sugessted concomitant SVDs and retinopathy is associated with a profile of vascular cognitive impairment. In this study, the investigators try to explore the new pathological mechanism of SVD, the new predictors for SVD progression, and the association with cognitive Impairment, based on digital retinal images and brain multimodal imaging technique.
- Being tested
- multimodal magnetic resonance imaging
- Medical subject headings
- Cerebral Small Vessel Diseases, Retinal Diseases, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
multimodal magnetic resonance imagingOther
Also called retinal digital images, neuropsychological testing, Blood samples collection
multimodal magnetic resonance imaging included T1, FLAIR, MRA, PWI and/or ASL, DTI, DKI, SWI, fMRI
| Study group | Role | What they receive |
|---|---|---|
| Individuals with SVDs | Individuals with at least one following imaging finding: recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, or brain atrophy on baseline brain MRI. Receives: Other: multimodal magnetic resonance imaging | |
| Individuals without SVDs | Individuals without any following imaging finding: recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, or brain atrophy on baseline brain MRI. Receives: Other: multimodal magnetic resonance imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive state
Cognitive state based on Mini-mental State Examination
Measured: 1year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2018
- Study start1 Jan 2010
- Primary completion30 Dec 2030 (estimated)
- Study completion30 Jun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Cerebral Small Vessel DiseasesStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- 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
- 1,000 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03542734
- Sponsor's protocol ID
- CIRCLE-CHINA
- Acronym
- CIRCLE
- Status last verified
- Jan 2023
- First submitted
- 20 May 2018
- Last updated
- 6 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Chen L, Zhong W, Chen H, Zhou Y, Ran W, He Y, Zhang T, Zhu X, Xu X, Yuan C, Lou M. ORIENT Diet: A Potential Neuroprotective Dietary Pattern for Chinese Stroke High-Risk Population. J Am Med Dir Assoc. 2025 Jan;26(1):105331. doi: 10.1016/j.jamda.2024.105331. Epub 2024 Oct 30.
PubMed 39488333Lee DA, Lee HJ, Jo G, Park KM. Choroid plexus volumes in patients with transient global amnesia: A retrospective study. Medicine (Baltimore). 2024 Oct 11;103(41):e40077. doi: 10.1097/MD.0000000000040077.
PubMed 39465804Zhao Y, Zhou Y, Zhou H, Gong X, Luo Z, Li J, Sun J, Lou M, Yan S. Low-density lipoprotein cholesterol, statin therapy, and cerebral microbleeds: The CIRCLE study. Neuroimage Clin. 2023;39:103502. doi: 10.1016/j.nicl.2023.103502. Epub 2023 Aug 22.
PubMed 37643520Zhu X, Zhou Y, Zhong W, Li Y, Wang J, Chen Y, Zhang R, Sun J, Sun Y, Lou M. Higher Functional Connectivity of Ventral Attention and Visual Network to Maintain Cognitive Performance in White Matter Hyperintensity. Aging Dis. 2023 Aug 1;14(4):1472-1482. doi: 10.14336/AD.2022.1206.
PubMed 37163435Zhang K, Zhou Y, Zhang W, Li Q, Sun J, Lou M. MRI-visible perivascular spaces in basal ganglia but not centrum semiovale or hippocampus were related to deep medullary veins changes. J Cereb Blood Flow Metab. 2022 Jan;42(1):136-144. doi: 10.1177/0271678X211038138. Epub 2021 Aug 25.
PubMed 34431378Zhang W, Zhou Y, Wang J, Gong X, Chen Z, Zhang X, Cai J, Chen S, Fang L, Sun J, Lou M. Glymphatic clearance function in patients with cerebral small vessel disease. Neuroimage. 2021 Sep;238:118257. doi: 10.1016/j.neuroimage.2021.118257. Epub 2021 Jun 10.
PubMed 34118396
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Associations of Retinal Microvascular Signs and Brain Imaging Markers With Cognitive Impairment in Patients With Small Vessel Disease
- ClinicalTrials.gov ID
- NCT03542734
- Acronym / sponsor ID
- CIRCLE / CIRCLE-CHINA
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 1 Jan 2010 (actual)
- Primary completion
- 30 Dec 2030 (estimated)
- Study completion
- 30 Jun 2031 (estimated)
- First posted
- 31 May 2018 (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.
The CIRCLE study is a single-center prospective observational study that enrolled individuals with cerebral small vessel disease (SVD), while free of known dementia or stroke (both cerebral infarction and hemorrhage). The patients will receive neuropsychological testing, retinal digital images and multimodal magnetic resonance imaging (MRI). Blood samples will also be collected. Recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy will be evaluated on both baseline and follow-up brain MRIs. The investigators will explore the predictors of preogression of SVD and cognitive deficits.
Detailed description
Cerebral small vessel disease (SVD) is commonly detected in elderly individuals, and patients with stroke or neurodegenerative disease. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. Previous studies indicated that SVD was associated with an increased risk of stroke and stroke recurrence, cognitive deficits, physical disabilities, and mortality. However the pathogenesis of SVD is largely unknown. Little is known about how SVD lesions contribute to neurological or cognitive symptoms, and the association with risk factors. Recent data sugessted concomitant SVDs and retinopathy is associated with a profile of vascular cognitive impairment. In this study, the investigators try to explore the new pathological mechanism of SVD, the new predictors for SVD progression, and the association with cognitive Impairment, based on digital retinal images and brain multimodal imaging technique.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Years
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Individuals with SVDs | – | Other: multimodal magnetic resonance imagingIndividuals with at least one following imaging finding: recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, or brain atrophy on baseline brain MRI. |
| Individuals without SVDs | – | Other: multimodal magnetic resonance imagingIndividuals without any following imaging finding: recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, or brain atrophy on baseline brain MRI. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Residents of certain towns
Key inclusion criteria (2 listed)
- Adult (≥40y; no upper limit)
- Free of known dementia or stroke (both cerebral infarction and hemorrhage)
Key exclusion criteria (3 listed)
- Any MRI contraindications
- Serious head injury (resulting to loss of consciousness) or received intracranial surgery
- Suffering from cancer
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 |
|---|---|---|
| multimodal magnetic resonance imagingAlso: retinal digital images, neuropsychological testing, Blood samples collectionmultimodal magnetic resonance imaging included T1, FLAIR, MRA, PWI and/or ASL, DTI, DKI, SWI, fMRI | Other | Individuals with SVDs, Individuals without SVDs |
Primary outcome
Cognitive state
Time frame: 1year
Cognitive state based on Mini-mental State Examination
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 6 Feb 2023.
- Derived from this study: PubMed 39488333Chen L, Zhong W, Chen H, Zhou Y, Ran W, He Y, Zhang T, Zhu X, Xu X, Yuan C, Lou M. ORIENT Diet: A Potential Neuroprotective Dietary Pattern for Chinese Stroke High-Risk Population. J Am Med Dir Assoc. 2025 Jan;26(1):105331. doi: 10.1016/j.jamda.2024.105331. Epub 2024 Oct 30.
- Derived from this study: PubMed 39465804Lee DA, Lee HJ, Jo G, Park KM. Choroid plexus volumes in patients with transient global amnesia: A retrospective study. Medicine (Baltimore). 2024 Oct 11;103(41):e40077. doi: 10.1097/MD.0000000000040077.
- Derived from this study: PubMed 37643520Zhao Y, Zhou Y, Zhou H, Gong X, Luo Z, Li J, Sun J, Lou M, Yan S. Low-density lipoprotein cholesterol, statin therapy, and cerebral microbleeds: The CIRCLE study. Neuroimage Clin. 2023;39:103502. doi: 10.1016/j.nicl.2023.103502. Epub 2023 Aug 22.
- Derived from this study: PubMed 37163435Zhu X, Zhou Y, Zhong W, Li Y, Wang J, Chen Y, Zhang R, Sun J, Sun Y, Lou M. Higher Functional Connectivity of Ventral Attention and Visual Network to Maintain Cognitive Performance in White Matter Hyperintensity. Aging Dis. 2023 Aug 1;14(4):1472-1482. doi: 10.14336/AD.2022.1206.
- Derived from this study: PubMed 34431378Zhang K, Zhou Y, Zhang W, Li Q, Sun J, Lou M. MRI-visible perivascular spaces in basal ganglia but not centrum semiovale or hippocampus were related to deep medullary veins changes. J Cereb Blood Flow Metab. 2022 Jan;42(1):136-144. doi: 10.1177/0271678X211038138. Epub 2021 Aug 25.
- Derived from this study: PubMed 34118396Zhang W, Zhou Y, Wang J, Gong X, Chen Z, Zhang X, Cai J, Chen S, Fang L, Sun J, Lou M. Glymphatic clearance function in patients with cerebral small vessel disease. Neuroimage. 2021 Sep;238:118257. doi: 10.1016/j.neuroimage.2021.118257. Epub 2021 Jun 10.
- Individual participant dataSharing planned: Undecided
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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.
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 Cerebral Small Vessel Diseases and Retinopathy, run by Second Affiliated Hospital, Zhejiang University, School of Medicine 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 2 inclusion and 3 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 6 Feb 2023. 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 Min Lou, Ph.D (13958007213, loumingxc@vip.sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive state (time frame: 1year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03542734, which also lists 6 linked publications.
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 6 Feb 2023.