Primary objective:To determine BBB integrity and the interplay with microvessel function including PVS and CVR response to CO2 breathing challenge in sporadic and monogenic presentations of human SVDs.Secondary objective:To determine the…
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* BBB integrity as assessed using DCE-MRI brain scan
* CVR as determined by BOLD MRI brain scan response to hypercapnic challenge
(CO2 breathing as vasodilative stimulus)
* PVS score, count, and volume on structural MRI brain scan, assessed using
validated methods
Secondary outcome
* BP parameters (peak systolic, systolic, mean, diastolic arterial pressures,
pulse pressures, and variability)
* Systemic measures of vascular stiffness (PWV)
* CSF pulsatility as an index of rate of passage of pulse waves through the
brain (stiffness), measured using MRI brain scan.
* Structural MRI markers of SVD * WMH, PVS, lacunes, microbleeds, individually
and by total SVD score.
* Circulating immune cells identified by FACS analysis
Background summary
Cerebral small vessel diseases (SVDs) are a major cause of stroke and dementia,
and yet there is no targeted treatment. Progress in understanding the
mechanisms that drive microvascular dysfunction and brain damage in SVDs has
been elusive, until now. Investigate@SVDs is part of a coordinated programme to
elucidate key mechanisms common to different SVDs, and determine how these
mechanisms contribute to individual SVDs (SVDs@Target Project, funded by the
European Horizon 2020 Scheme).
Investigate@SVDs will assess factors that drive brain microvascular dysfunction
in SVD. We will use MRI brain scans to assess microvascular function by
measuring blood-brain barrier permeability, CVR, and cerebral pulsatility to
understand the interplay of microvascular dysfunction and clinical and
radiological features of SVD. Measurement of BPv over one week will help
understand the role of the systemic circulation in the development of brain
microvascular dysfunction. Finally, the role of vascular inflammation will be
investigated by characterisation of circulating immune cells.
Study objective
Primary objective:
To determine BBB integrity and the interplay with microvessel function
including PVS and CVR response to CO2 breathing challenge in sporadic and
monogenic presentations of human SVDs.
Secondary objective:
To determine the relationship between BBB leakage and (i) BP and its
variability and (ii) structural MRI markers of SVDs in sporadic and monogenic
presentations of human SVDs.
Identification and characterization of circulating immune cells in sporadic and
monogenic presentations of human SVDs and the correlation with BBB
permeability, microvascular function and structural MRI markers.
Study design
Investigate@SVDs is an observational study
Study burden and risks
Participants will attend for two visits over a period of eight days. At the
first visit, patients proceed to have a full medical history and examination
performed, cognitive testing will be performed and blood samples will be taken
for analysis Participants receive a BP machine to perform home BP monitoring
with the device over the next seven days. Participants will attend for a second
visit on day 7+/-1day and undergo brain MRI to measure BBB permeability, CVR
and pulsatility of ICA and CSF flow. The total time to acquire all MRI
sequences is around two hours. For the individual patient, participation in
the study will have no direct benefit. In future perspectives, the results
might advance our knowledge of SVD pathophysiology which can lead to better
treatment options.
Oxfordlaan 10
Maastricht 6202 AZ
NL
Oxfordlaan 10
Maastricht 6202 AZ
NL
Listed location countries
Age
Inclusion criteria
* Symptomatic SVD defined as
- a history compatible with clinical lacunar stroke syndrome in the last 5
years with a recent small subcortical infarct visible on MRI scan or CT scan
compatible with the clinical syndrome.
-or cognitive impairment defined as visiting a memory clinic and a clinical
dementia rating score of * 0.5, and capacity to consent with confluent deep WMH
on MRI (defined on the Fazekas scale as deep WMH score * 2).
- or a diagnosis of CADASIL established by molecular genetic testing of the
NOTCH3 gene (presence of an archetypical, cysteine-affecting mutation) or the
presence of granular osmiophilic material in ultrastructural, electron
microscopy analysis of skin biopsy.
* Age 18 years or older
* Ability to undergo MRI
* Capacity to give written informed consent
* Independent in activities of daily living (Modified Rankin score <3)
Exclusion criteria
* Inclusion criteria are not met
* Unwillingness or inability to give written consent
* Pregnant or breastfeeding women, women of childbearing age not taking
contraception.
* Contraindications to MRI: pacemaker, metallic foreign body (including
aneurysm clip in the brain), claustrophobia, pregnancy, neurostimulator,
pacemaker or other kinds of implanted devices or insulin pump.
* Contraindications to gadolinium contrast agent used for MRI
* Other major neurological or psychiatric conditions affecting the brain and
interfering with the study design (e.g. multiple sclerosis)
* In case of clinical lacunar stroke syndrome other causes of stroke such as
*50% luminal stenosis in large arteries supplying the area of ischaemia,
major-risk cardioembolic source of embolism, other specific causes of stroke
identified (e.g. arteritis, dissection, migraine/vasospasm, drug misuse)
* Other stroke risk factor requiring immediate intervention that would preclude
involvement in the study
* Renal impairment (eGFR <30 ml/min)
* Panic disorder
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ISRCTN | ISRCTN10514229 |
| CCMO | NL58997.068.16 |