MRI-markers to Monitor Small Vessel Disease Dynamics in the Prognosis of Small Vessel Disease-associated, Cerebrovascular Events (MRI-PRO-SVD)

MRI-markers to Monitor Small Vessel Disease Dynamics in the Prognosis of Small Vessel Disease-associated, Cerebrovascular Events - a Prospective Cohort Study

This is a nested cohort study in the PRO-SVD cohort. Small vessel disease is a chronic disease and is thought to progress over time. MRI is the gold standard to diagnose small vessel disease, but data on MRI-visible disease progression are scarce. Complications of small vessel disease as well as location pattern, distribution and severity of these MRI small vessel disease markers differ according to the underlying phenotype. The primary aim of this project is to investigate individual small vessel disease burden progression detected by MRI in survivors or intracerebral hemorrhage.

Study Overview

• Status: Recruiting
• Conditions: Cerebral Small Vessel Diseases; Intracerebral Hemorrhage; CAA - Cerebral Amyloid Angiopathy
• Intervention / Treatment: Diagnostic test: Combined 3- and 7 Tesla-MRI

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Marianne Kormann; Phone Number: +41 31 632 70 00; Email: studien.stroke@insel.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Department of Neurology, Inselspital Bern University Hospital
    • Contact: David J Seiffge, MD, Prof; Phone Number: +41 31 632 70 00; Email: david.seiffge@insel.ch
    • Sub-Investigator: Martina B Goeldlin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

50 consecutive patients with cerebral small vessel disease-related intracerebral hemorrhage admitted to the Inselspital Bern. Patients will undergo combined 3/7 Tesla-MRI according to a standardised small vessel disease MRI protocol at 3 timepoints.

A control group consisting of 10 clinically asymptomatic subjects will undergo the same MRI protocol at one timepoint.

Description

For patients with intracerebral hemorrhage

Inclusion Criteria:

• Patient participating in the PRO-SVD cohort
• Symptomatic intracranial hemorrhage
• Written informed consent provided by patient or next-of-kin
• No contraindications against MRI

Exclusion Criteria:

• Patient unsuitable for MRI follow-ups (e.g. claustrophobia)
• Patients unlikely to attend 1-year follow-up

For healthy controls

Inclusion Criteria:

• Clinically healthy person ≥ 55 years
• Written informed consent provided by the healthy control
• No contraindications against MRI

Exclusion Criteria:

• Known or suspected cerebral small vessel diseases or presence of concurrent diseases potentially mimicking small vessel disease (e.g. multiple sclerosis, previous heart surgery etc.)
• Pre-existing dementia, cognitive decline or disorder of the central nervous system.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with intracerebral hemorrhage; Patients with symptomatic intracranial hemorrhage (defined as non-traumatic intracerebral hemorrhage or convexity, non-aneurysmal subarachnoid hemorrhage) enrolled in the PRO-SVD study	Diagnostic test: Combined 3- and 7 Tesla-MRI; 7 Tesla-MRI including the following sequences: susceptibility weighted imaging (SWI), T1, T2, FLAIR, quantitative mapping sequences (T1mapping, qSM)
Healthy controls; Clinically healthy persons of at least 55 years of age	Diagnostic test: Combined 3- and 7 Tesla-MRI; 7 Tesla-MRI including the following sequences: susceptibility weighted imaging (SWI), T1, T2, FLAIR, quantitative mapping sequences (T1mapping, qSM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease progression	Composite endpoint of a new, clinically symptomatic ischaemic or haemorrhagic event as defined by the treating physician and/or any increase in small vessel disease and/or cerebral amyloid angiopathy burden according to small vessel disease burden score (range 0-4 points, higher score means higher small vessel disease burden) or cerebral amyloid angiopathy burden score (range 0-6 points, higher score means higher cerebral amyloid angiopathy burden), respectively.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI-defined disease progression	Any increase in small vessel disease (SVD) and/or cerebral amyloid angiopathy (CAA) burden according to small vessel disease burden score (range 0-4 points, higher score means higher small vessel disease burden) or cerebral amyloid angiopathy burden score (range 0-6 points, higher score means higher cerebral amyloid angiopathy burden), respectively.	24 months
Increase in number of SVD-attributable, ischaemic lesions	Composite outcome defined as any increase in numeric count for lacunes and/or increase in perivascular space severity scale (0/1-10 PVS/11-20 PVS/21-40 PVS/>40 PVS) and/or increase in periventricular or deep separate white matter Fazekas scale.	24 months
Increase in number of SVD-attributable, haemorrhagic lesions	Composite outcome defined as any increase in numeric count for cerebral microbleeds and/or increase in cortical superficial siderosis multifocality score.	24 months
Increase in perivascular space severity scale	Defined as any increase in perivascular space (PVS) severity scale (0/1-10 PVS/11-20 PVS/21-40 PVS/>40 PVS, higher number of PVS means higher small vessel disease burden).	24 months
Clinical, vascular outcome event	Composite endpoint including any of the following, clinically apparent events: ischaemic stroke as diagnosed by CT or MRI and causing a corresponding clinical deficit (as assessed by the treating physician); intracerebral haemorrhage as diagnosed by CT or MRI and causing a corresponding clinical deficit (as assessed by the treating physician); systemic vascular event defined as radiological or clinical evidence of arterial hypoperfusion and judged by the treating physician to be due to an atherosclerotic or embolic cause.	24 months
Functional outcome	Modified Rankin Scale (ordinal scale, range 0-6 with 0 corresponding to no symptoms at all and 6 corresponding to death).	24 months
New cognitive impairment	Montreal Cognitive Assessment (MoCA, range 0-30 points) < 26 points (corresponding to impaired cognitive function) and/or new impairment in activities of daily living as defined by the treating physician .	24 months

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Principal Investigator: David J Seiffge, Prof, MD, Department of Neurology, Inselspital Bern University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: February 9, 2023
• First Submitted That Met QC Criteria: March 6, 2023
• First Posted (Actual): March 17, 2023

Study Record Updates

• Last Update Posted (Actual): March 17, 2023
• Last Update Submitted That Met QC Criteria: March 6, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Ischemic stroke; Intracerebral hemorrhage; Cerebral amyloid angiopathy; Cerebral small vessel disease; Hypertensive deep perforator arteriopathy; 7 Tesla-MRI; Ultra high-field MRI
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Proteostasis Deficiencies; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Intracranial Hemorrhages; Amyloidosis, Familial; Amyloidosis; Hemorrhage; Cerebral Hemorrhage; Cerebral Small Vessel Diseases; Cerebral Amyloid Angiopathy; Cerebral Amyloid Angiopathy, Familial
• Other Study ID Numbers: 2021-02006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data sharing can be discussed by qualified researchers with the principal investigator upon reasonable request and might be subject to prior additional approval by the respective ethical board.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No