Sporadic small vessel disease - stroke, cognitive impairment Circulatory System
Conditions
Interventions
After answering some questions about their health, the subjects will have a blood pressure cuff put on their arm to wear for a week while doing their usual activities. This measures blood pressure con
Sponsors
Academic and Clinical Central Office for Research and Development (ACCORD)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 years or older 2. Able to undergo MRI 3. Capacity to give written informed consent 4. Symptomatic SVD defined as: 4.1. A history of 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 4.2. 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 (GOM) in ultrastructural, electron microscopy analysis of skin biopsy *On MRI, a recent infarct is defined as a DWI lesion on the acute MRI scan. On CT, recent infarct is defined as a novel lacune on CT within 3 weeks after the event that was not visible on the admission CT. or cognitive impairment defined as visiting a memory clinic and a clinical dementia rating [CDR] score of = 0.5, and capacity to consent with confluent deep white matter hyperintensities (WMH) on MRI (defined on the Fazekas scale as deep WMH score = 2)
Exclusion criteria
Exclusion criteria: 1. Inclusion criteria are not met 2. Unwillingness or inability to give written consent 3. Pregnant or breastfeeding women, women of childbearing age not taking contraception. 4. Acceptable contraception in women of childbearing age is a “highly effective” contraceptive measure as defined by the Clinical Trials Facilitation Group (http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf) and includes combined (oestrogen and progesterone containing) or progesterone-only contraception associated with inhibition of ovulation, or intrauterine device or bilateral tubal occlusion 5. Contraindications to MRI (pacemaker, aneurysm clip, cochlear implant etc.) 6. Contraindications to gadolinium contrast agent used for MRI 7. Other major neurological or psychiatric conditions affecting the brain and interfering with the study design (e.g. multiple sclerosis) 8. In case of clinical lacunar stroke syndrome other causes of stroke such as: 8.1. =50% luminal stenosis (NASCET) in large arteries supplying the area of ischaemia 8.2. Major-risk cardioembolic source of embolism (permanent or paroxysmal atrial fibrillation, sustained atrial flutter, intracardiac thrombus, prosthetic cardiac valve, atrial myxoma or other cardiac tumours, mitral stenosis, recent (<4 weeks) myocardial infarction, left ventricular ejection fraction less than 30%, valvular vegetations, or infective endocarditis) 8.3. Other specific causes of stroke identified (e.g. arteritis, dissection, migraine/vasospasm, drug misuse) 9. Other stroke risk factor requiring immediate intervention that would preclude involvement in the study 10. Renal impairment (eGFR <30 ml/min)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Blood brain barrier leakiness is measured during the magnetic resonance scan from the gadolinium contrast agent uptake in the brain over 20 minutes after intravenous injection. The resulting contrast-time curve is modelled statistically to calculate contrast retention (leak) in different areas of the brain. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Cerebrovascular reactivity to inhaled carbon dioxide is measured once prior to blood brain barrier leakiness 2. Blood pressure (systolic, diastolic, mean blood pressure, pulse pressure, and variability in blood pressure) is measured continuously for seven days prior to blood brain barrier leakiness scanning 3. Vascular stiffness is measured immediately after blood-brain barrier leakiness scanning using pulse wave velocity | — |
Countries
Germany, Netherlands, Scotland, United Kingdom
Outcome results
None listed