INflammation and Small Vessel Disease Study
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age40+
SponsorUniversity of Cambridge
About this trial
A prospective observational cohort study in patients with cerebral small vessel disease deterring whether changes in systemic inflammation predict brain white matter damage measured using MRI and cognitive decline. This is a study funded by a joint BHF-Dutch Heart Foundation research grant and will be conducted in both Cambridge UK and Nijmegen Netherlands with 100 of the 200 total participants recruited at each site, and data from both sites analysed together.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Have given written informed consent to participate
Be aged 40 years and over
Clinical lacunar stroke syndrome with lacunar infarct, as defined by the Standards for Reporting Vascular Changes on Neuroimaging (STRIVE) criteria
And/OR Symptoms of cognitive impairment due to SVD with lacunar infarct on MRI
Disqualifiers
Unable/unwilling to consent including lack of capacity to consent
Contraindications to taking part in MRI study as assessed by the local MRI safety questionnaire, e.g., pacemaker
Vaccination or infection with fever in preceding month
Cardioembolic source
Trial population
Patients with symptomatic cerebral small vessel disease.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
200 Participants
are grouped into 1 trial groupGroup A: INSVD Cohort
Trial outcomes
Primary outcomes
1
Peripheral inflammatory markers
Measured from blood sample: a panel of circulating inflammatory proteins. In addition, we will perform extensive phenotyping of peripheral blood mononuclear cells (PBMC) and monocytes, including cytokine production capacity, and transcriptomic and (epi)genetic analyses.
Time frame
Baseline (August 2022 - )2
White matter microstructure
Measured by diffusion-weighted imaging: mean diffusivity, fractional anisotropy, peak width of skeletonized mean diffusivity, etc. Diffusion data will be analysed by the creation of voxel by voxel maps of standard diffusion parameters such as mean diffusivity and fraction anisotropy and also by the construction of estimations of white matter tracts using tractography algorithms.
Time frame
Baseline + Follow-up (August 2022 - )Secondary outcomes
1
Cognitive performance and decline
Multi-domain cognitive assessment battery will be administered at baseline and at 2-year follow-up visits. The INSVD study employs a test battery of widely-used neuropsychological tasks we have previously optimised to characterise cognitive impairment in SVD which has prominent executive dysfunction and slowing of information processing speed. Years of education will be collected as a covariate in statistical modelling.
Time frame
Baseline + Follow-up (August 2022 - )2
Blood brain barrier permeability
Dynamic contrast-enhanced (DCE) MRI will be collected for the quantification of subtle BBB leakage throughout the brain. All subjects undergo repeat T1 mapping with the injection of a contrast agent to assess BBB permeability. T1 will be mapped prior to injection, this will be followed by an injection of a gadolinium based MRI contrast agent which will be administered by a medically qualified staff member appropriately trained to deal with allergic reactions. Gadolinium is non- radioactive and already in routine clinical use as part of MR angiography studies to visualise vascular anatomy.
Time frame
Baseline + Follow-up (August 2022 - )3
Other MRI markers (e.g., brain volume, other measures of SVD)
Brain imaging will be conducted on identical Siemens 3T PRISMA scanners in Cambridge (Wolfson Brain Imaging Centre) and Nijmegen (Donders Institute for Brain, Cognition \& Behaviour). Identical sequences are acquired at both sites using a harmonised MRI protocol at both baseline and 2-year follow-up.
Time frame
Baseline + Follow-up (August 2022 - )Sponsors and contacts
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University of Cambridge
Lead sponsor
Radboud University Medical Center
Collaborator
Wolfson Brain Imaging Centre
Collaborator
Source ClinicalTrials.gov