NCT05746221

Brief Summary

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P75+ for all trials

Timeline
2mo left

Started Aug 2022

Longer than P75 for all trials

Geographic Reach
2 countries

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress94%
Aug 2022Jul 2026

Study Start

First participant enrolled

August 10, 2022

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

February 17, 2023

Completed
10 days until next milestone

First Posted

Study publicly available on registry

February 27, 2023

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2026

Last Updated

February 27, 2023

Status Verified

February 1, 2023

Enrollment Period

4 years

First QC Date

February 17, 2023

Last Update Submit

February 17, 2023

Conditions

Cerebral Small Vessel DiseasesInflammationStroke

Keywords

Cerebral small vessel diseaseInflammationStrokeCerebrovascular diseaseLacunar strokeWhite matter diseaseCognitive impairmentBlood brain barrier

Outcome Measures

Primary Outcomes (2)

  • 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.

    Baseline (August 2022 - )

  • 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.

    Baseline + Follow-up (August 2022 - )

Secondary Outcomes (3)

  • Cognitive performance and decline

    Baseline + Follow-up (August 2022 - )

  • Blood brain barrier permeability

    Baseline + Follow-up (August 2022 - )

  • Other MRI markers (e.g., brain volume, other measures of SVD)

    Baseline + Follow-up (August 2022 - )

Study Arms (1)

INSVD Cohort

200 patients with cerebral small vessel disease - 100 recruited from Cambridge, UK; 100 recruited from Nijmegen, Netherlands.

Eligibility Criteria

Age40 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Patients with symptomatic cerebral small vessel disease.

You may qualify if:

  • Have given written informed consent to participate
  • Be aged 40 years and over
  • Have symptomatic cerebral small vessel disease (SVD) defined as:
  • 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
  • And/OR Gait apraxia/motor impairment presumed due to SVD with lacunar infarct on MRI

You may not qualify if:

  • 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
  • Any stroke cause other than SVD including:
  • Cardioembolic source
  • Carotid or vertebral stenosis \> 50% measured on NASCET (North American Symptomatic Carotid Endarterectomy Trial) criteria
  • Myocardial infarction in past year
  • Auto-immune/auto-inflammatory disease
  • Use of immunomodulating drugs
  • Estimated glomerular filtration rate (eGFR) =\<59 ml/min/1.73m2 within past 3 months for Cambridge, and eGFR =\<29 ml/min/1.73m2 within past 3 months for Nijmegen, in line with local guidelines. Estimated GFR will be calculated using the Modification of Diet in Renal Disease (MDRD) equation: 186 x (Creatinine / 88.4)-1.154 x (Age)- 0.203 x (0.742 if female) x (1.210 if black). Creatinine will be checked within 3 months of the MRI, and if this has not been done as part of clinical care it will be performed as a research procedure.
  • Another diagnosed chronic neurological condition (e.g. Alzheimer's, Parkinson's disease, motor neurone disease, multiple sclerosis).
  • Limited life expectancy due to another illness or chronic condition making the 2-year follow-up difficult (e.g. widespread malignancy).
  • Known monogenic cause of small vessel disease (e.g. CADASIL - Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Radboud University Medical Centre

Nijmegen, Netherlands

RECRUITING

University of Cambridge

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

RECRUITING

Related Publications (1)

  • Low A, van Winden S, Cai L, Kessels RPC, Maas MC, Morris RG, Nus M, Tozer DJ, Tuladhar A, van der Kolk A, Wolters R, Mallat Z, Riksen NP, Markus H, de Leeuw FE. Immune regulation and blood-brain barrier permeability in cerebral small vessel disease: study protocol of the INflammation and Small Vessel Disease (INSVD) study - a multicentre prospective cohort study. BMJ Open. 2024 Feb 26;14(2):e084303. doi: 10.1136/bmjopen-2024-084303.

    PMID: 38413153DERIVED

Related Links

MeSH Terms

Conditions

Cerebral Small Vessel DiseasesInflammationStrokeCerebrovascular DisordersStroke, LacunarLeukoencephalopathiesCognitive Dysfunction

Condition Hierarchy (Ancestors)

Brain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsThrombotic StrokeIschemic StrokeBrain InfarctionInfarctionIschemiaNecrosisCognition DisordersNeurocognitive DisordersMental Disorders

Study Officials

  • Hugh S Markus

    University of Cambridge

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Hugh S Markus

CONTACT

+44 (0)1223 856661hsm32@medschl.cam.ac.uk

Audrey Low

CONTACT

+44 (0) 1223 216619al927@medschl.cam.ac.uk

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

February 17, 2023

First Posted

February 27, 2023

Study Start

August 10, 2022

Primary Completion (Estimated)

July 31, 2026

Study Completion (Estimated)

July 31, 2026

Last Updated

February 27, 2023

Record last verified: 2023-02

Data Sharing

IPD Sharing
Will share

We plan to make this study data available for other researchers throughout the world. This open access data would be completely anonymised and will not include information that could be used to identify the subjects. This will include stripping the skull from images so that faces cannot be reconstructed.

Locations

NL(1)GB(1)