Cerebral Small Vessel DiseasesNCT06416371
Retinal Vessel Leakage in Cerebral Small Vessel Disease
An observational study of Cerebral Small Vessel Diseases and Lacunar Stroke, run by University of Edinburgh at 1 site in United Kingdom.
Trial summary
The goal of this observational study is to learn about leakage from retinal vessels in cerebral small vessel disease. The main questions it aims to answer are: Does retinal vessel leakage occur in cerebral small vessel disease? If it does, is the severity of retinal vessel leakage similar to the severity of cerebral… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cerebral Small Vessel Diseases, Lacunar Stroke, Vascular Dementia
- What is being tested?
- Fundus fluorescein angiography, with ultrawide field retinal imaging
- Type of treatment
- Injection or infusion
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 13 Jan 2025to 15 Feb 2029
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults >18 years old with mild ischaemic stroke with a modified Rankin scale (mRS) greater or equal to 2 at recruitment presenting to Edinburgh/Lothian stroke services. For details see Clancy, et al (2021) Rationale and design of a longitudinal study of cerebral small vessel diseases, clinical and imaging outcomes in patients presenting with mild ischaemic stroke: Mild Stroke Study 3. European Stroke Journal 6:81-88. https://doi.org/10.1177/2396987320929617
Who may be able to join
- Membership in the Mild Stroke Study 3 cohort
- Contrast enhanced MRI within 12 months
- Clear optical media in both eyes, as assessed by study investigator
- Best corrected visual acuity (near vision) ≥N36
Who cannot join
- Any condition known to cause retinal leakage (i.e., worse than background diabetic retinopathy, retinal vein occlusion, active uveitis, wet age-related macular degeneration, malignant hypertension)
- Previous treatment for retinal leakage (retinal laser, intravitreal anti-VEGF)
- Recent eye surgery
- Shallow anterior chambers as assessed by torch test
- Pregnancy, renal failure
- Severe dementia
Show all 10Show fewer
- Known allergy to fluorescein
- History of allergy such as food or drug induced urticaria or history of bronchial asthma
- Any other severe or acute medical or psychiatric conditions
- Inability to give informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
NHS Lothian
Edinburgh
Ian Maccormick, imaccorm@ed.ac.uk
About this study
Official title: Retinal Vessel Leakage in Cerebral Small Vessel Disease: a Sub-study of the Mild Stroke Study 3
The goal of this observational study is to learn about leakage from retinal vessels in cerebral small vessel disease. The main questions it aims to answer are:
- Does retinal vessel leakage occur in cerebral small vessel disease?
- If it does, is the severity of retinal vessel leakage similar to the severity of cerebral small vessel disease generally?
Read more
Participants will be tested using fluorescein angiography. This involves an intravenous injection of fluorescent dye, and is a very sensitive way to find leakage from retinal blood vessels.
Participants will have already had brain scans and other examinations and tests to measure the severity of their cerebral small vessel disease. Our new retinal images will complement the information from these previous tests.
Read the detailed description
Cerebral small vessel disease (SVD) is a common cause of stroke and dementia. The molecular causes are unclear, limiting new therapies. Breakdown of the blood-brain barrier (BBB) is characteristic and may damage brain tissue. However, specialist MRI scans to measure BBB breakdown are expensive and time-consuming.
In contrast, measuring leakage from retinal blood vessels is relatively simple. The blood-retina barrier is very similar to the BBB, and SVD is likely to damage retinal and brain blood vessels in the same way. If so, then retinal angiography could be used to study SVD pathogenesis and measure the effect of new treatments with much greater resolution and lower cost than MRI.
We have three aims:
- Test the feasibility of fluorescein angiography in people with SVD
- Discover if retinal vessel leakage occurs people with SVD
- Discover whether the severity of retinal vessel leakage is associated with clinical features of SVD
We will recruit participants from a well-established cohort of people with SVD - the Mild Stroke Study 3 (MSS3).
- Being tested
- Fundus fluorescein angiography, with ultrawide field retinal imaging
- Medical subject headings
- Cerebral Small Vessel Diseases, Stroke, Lacunar, Dementia, Vascular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fundus fluorescein angiography, with ultrawide field retinal imagingDiagnostic test
Intravenous injection of sodium fluorescein for angiography of retinal blood vessels
What is being measured
The primary outcome is the main question the study is designed to answer.
Retinal vessel leakage by automated segmentation
The presence and severity of retinal vessel leakage will be measured for each eye in terms of change in pixel brightness over the duration of the angiogram.
Measured: within one angiogram
Retinal vessel leakage by manual grading
The presence and severity of retinal vessel leakage will be measured using an manual ordinal grading scale
Measured: within one angiogram
Secondary outcomes (8)
Baseline blood-brain barrier breakdown
BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium
Measured: Within one MRI scan
White matter hyperintensity (WMH) volume adjusted for brain volume
This is measured from the most recent structural MRI scan
Measured: Within one MRI scan
Change in white matter hyperintensity (WMH) volume adjusted for brain volume
This is measured by comparing the most recent structural MRI scan with the baseline structural MRI scan
Measured: Difference in MRI scans up to 5 years prior
Fazekas score
This is measured from the most recent structural MRI scan
Measured: Within one MRI scan
Change in Fazekas score
This is measured by comparing the most recent structural MRI scan with the baseline structural MRI scan
Measured: Difference in MRI scans up to 5 years prior
Baseline average leakage in white matter hyperintensities
BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium
Measured: Within one MRI scan
Baseline average leakage in deep grey matter
BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium
Measured: Within one MRI scan
Baseline number of leakage hotspots
BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium
Measured: Within one MRI scan
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2024
- Study start13 Jan 2025
- Primary completion15 Feb 2029 (estimated)
- Study completion15 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cerebral Small Vessel DiseasesStudies 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
- Cross-sectional
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06416371
- Sponsor's protocol ID
- AC24000
- Status last verified
- Mar 2026
- First submitted
- 15 Jan 2024
- Last updated
- 4 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Clancy U, Garcia DJ, Stringer MS, Thrippleton MJ, Valdes-Hernandez MC, Wiseman S, Hamilton OK, Chappell FM, Brown R, Blair GW, Hewins W, Sleight E, Ballerini L, Bastin ME, Maniega SM, MacGillivray T, Hetherington K, Hamid C, Arteaga C, Morgan AG, Manning C, Backhouse E, Hamilton I, Job D, Marshall I, Doubal FN, Wardlaw JM. Rationale and design of a longitudinal study of cerebral small vessel diseases, clinical and imaging outcomes in patients presenting with mild ischaemic stroke: Mild Stroke Study 3. Eur Stroke J. 2021 Mar;6(1):81-88. doi: 10.1177/2396987320929617. Epub 2020 Jun 5.
PubMed 33817338MacCormick IJ, Maude RJ, Beare NA, Borooah S, Glover S, Parry D, Leach S, Molyneux ME, Dhillon B, Lewallen S, Harding SP. Grading fluorescein angiograms in malarial retinopathy. Malar J. 2015 Sep 24;14:367. doi: 10.1186/s12936-015-0897-7.
PubMed 26403288
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Retinal Vessel Leakage in Cerebral Small Vessel Disease: a Sub-study of the Mild Stroke Study 3
- ClinicalTrials.gov ID
- NCT06416371
- Acronym / sponsor ID
- AC24000
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Study start
- 13 Jan 2025 (actual)
- Primary completion
- 15 Feb 2029 (estimated)
- Study completion
- 15 Feb 2029 (estimated)
- First posted
- 16 May 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.
The goal of this observational study is to learn about leakage from retinal vessels in cerebral small vessel disease. The main questions it aims to answer are:
- Does retinal vessel leakage occur in cerebral small vessel disease?
- If it does, is the severity of retinal vessel leakage similar to the severity of cerebral small vessel disease generally?
Participants will be tested using fluorescein angiography. This involves an intravenous injection of fluorescent dye, and is a very sensitive way to find leakage from retinal blood vessels.
Participants will have already had brain scans and other examinations and tests to measure the severity of their cerebral small vessel disease. Our new retinal images will complement the information from these previous tests.
Detailed description
Cerebral small vessel disease (SVD) is a common cause of stroke and dementia. The molecular causes are unclear, limiting new therapies. Breakdown of the blood-brain barrier (BBB) is characteristic and may damage brain tissue. However, specialist MRI scans to measure BBB breakdown are expensive and time-consuming.
In contrast, measuring leakage from retinal blood vessels is relatively simple. The blood-retina barrier is very similar to the BBB, and SVD is likely to damage retinal and brain blood vessels in the same way. If so, then retinal angiography could be used to study SVD pathogenesis and measure the effect of new treatments with much greater resolution and lower cost than MRI.
We have three aims:
- Test the feasibility of fluorescein angiography in people with SVD
- Discover if retinal vessel leakage occurs people with SVD
- Discover whether the severity of retinal vessel leakage is associated with clinical features of SVD
We will recruit participants from a well-established cohort of people with SVD - the Mild Stroke Study 3 (MSS3).
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults >18 years old with mild ischaemic stroke with a modified Rankin scale (mRS) greater or equal to 2 at recruitment presenting to Edinburgh/Lothian stroke services. For details see Clancy, et al (2021) Rationale and design of a longitudinal study of cerebral small vessel diseases, clinical and imaging outcomes in patients presenting with mild ischaemic stroke: Mild Stroke Study 3. European Stroke Journal 6:81-88. https://doi.org/10.1177/2396987320929617
Key inclusion criteria (4 listed)
- Membership in the Mild Stroke Study 3 cohort
- Contrast enhanced MRI within 12 months
- Clear optical media in both eyes, as assessed by study investigator
- Best corrected visual acuity (near vision) ≥N36
Key exclusion criteria (10 listed)
- Any condition known to cause retinal leakage (i.e., worse than background diabetic retinopathy, retinal vein occlusion, active uveitis, wet age-related macular degeneration, malignant hypertension)
- Previous treatment for retinal leakage (retinal laser, intravitreal anti-VEGF)
- Recent eye surgery
- Shallow anterior chambers as assessed by torch test
- Pregnancy, renal failure
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 |
|---|---|---|
| Fundus fluorescein angiography, with ultrawide field retinal imagingIntravenous injection of sodium fluorescein for angiography of retinal blood vessels | Diagnostic test | – |
Primary outcome
Retinal vessel leakage by automated segmentation
Time frame: within one angiogram
The presence and severity of retinal vessel leakage will be measured for each eye in terms of change in pixel brightness over the duration of the angiogram.
Retinal vessel leakage by manual grading
Time frame: within one angiogram
The presence and severity of retinal vessel leakage will be measured using an manual ordinal grading scale
8 secondary outcomes
Baseline blood-brain barrier breakdown
Time frame: Within one MRI scan
White matter hyperintensity (WMH) volume adjusted for brain volume
Time frame: Within one MRI scan
Change in white matter hyperintensity (WMH) volume adjusted for brain volume
Time frame: Difference in MRI scans up to 5 years prior
Fazekas score
Time frame: Within one MRI scan
Change in Fazekas score
Time frame: Difference in MRI scans up to 5 years prior
Baseline average leakage in white matter hyperintensities
Time frame: Within one MRI scan
Baseline average leakage in deep grey matter
Time frame: Within one MRI scan
Baseline number of leakage hotspots
Time frame: Within one MRI scan
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 4 Mar 2026.
- Background: PubMed 33817338Clancy U, Garcia DJ, Stringer MS, Thrippleton MJ, Valdes-Hernandez MC, Wiseman S, Hamilton OK, Chappell FM, Brown R, Blair GW, Hewins W, Sleight E, Ballerini L, Bastin ME, Maniega SM, MacGillivray T, Hetherington K, Hamid C, Arteaga C, Morgan AG, Manning C, Backhouse E, Hamilton I, Job D, Marshall I, Doubal FN, Wardlaw JM. Rationale and design of a longitudinal study of cerebral small vessel diseases, clinical and imaging outcomes in patients presenting with mild ischaemic stroke: Mild Stroke Study 3. Eur Stroke J. 2021 Mar;6(1):81-88. doi: 10.1177/2396987320929617. Epub 2020 Jun 5.
- Background: PubMed 26403288MacCormick IJ, Maude RJ, Beare NA, Borooah S, Glover S, Parry D, Leach S, Molyneux ME, Dhillon B, Lewallen S, Harding SP. Grading fluorescein angiograms in malarial retinopathy. Malar J. 2015 Sep 24;14:367. doi: 10.1186/s12936-015-0897-7.
- 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 Lacunar Stroke, run by University of Edinburgh at 1 site in United Kingdom.
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 4 inclusion and 10 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 4 Mar 2026. 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 United Kingdom. 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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Retinal vessel leakage by automated segmentation (time frame: within one angiogram). The study lists 2 primary outcomes in all. 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 NCT06416371, which also lists 2 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 4 Mar 2026.