Cerebral small vessel disease Circulatory System Stroke, not specified as haemorrhage or infarction
Conditions
Interventions
Current intervention as of 21/11/2019:
This project is a double blind randomised clinical trial which uses MRI and PET imaging at baseline and three months to study blood brain barrier permeability an
Sponsors
Cambridge University Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Clinical evidence of cerebral small vessel disease as evidenced by one or more of; 1.1. A lacunar stroke syndrome (e.g., pure motor stroke, pure sensory stroke, sensorimotor stroke or ataxic hemiparesis, or clumsy hand dysarthria syndrome) with a corresponding acute lacunar infarct on diffusion weighted imaging (DWI) for cases imaged (clinically) within 3 weeks of stroke or an anatomically compatible lacunar infarct on FLAIR/T1 MRI for cases imaged later after stroke (<=1.5 cm diameter) 1.2. Symptoms of cognitive impairment 1.3. Gait apraxia 2. Confluent white matter hyper-intensities on T2 weighted MRI 3. If a past history of stroke at least 3 months after last stroke to exclude BBB changes secondary to acute infarction
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 21/11/2019: 1. Unable/unwilling to consent 2. MMSE 1.5 cm – as many of these are striatocapsular infarcts caused by embolism 5. Evidence of cortical stroke 6. Any stroke cause other than SVD including: 6.1. Cardioembolic source 6.2. Carotid or vertebral stenosis > 50% measured on NASCET criteria 7. Estimated glomerular filtration rate (eGFR) =1.5 cm – as many of these are striatocapsular infarcts caused by embolism 5. Evidence of cortical stroke 6. Any stroke cause other than SVD including: 6.1. Cardioembolic source 6.2. Carotid or vertebral stenosis >50% measured on NASCET criteria 7. Estimated glomerular filtration rate (eGFR) =<59 ml/min/1.73m2 within past 3 months. Estimated GFR will be calculated using the Modification of Diet in Renal Disease (MDRD) equation: 186 x (Creatinine / 88.4)1.154x (Age) - 0.203 x (0.742 if female) x (1.210 if black) 8. Contraindications to taking part in MRI study, e.g., pacemaker 9. Inability to lie still in the PET/MR scanner for up to 75 minutes 10. Women who are of childbearing age, pregnant or breastfeeding 11. Meeting exclusions related to minocycline consumption, in particular: 12. Allergic to minocycline hydrochloride, other similar antibiotics 13. Have had complete kidney failure 14. Suffer from myasthenia gravis, have impaired liver or kidney function, Have systemic lupus erythematosus (SLE) 15. Suffer from increased pressure in the skull 16. Are sensitive to sunlight or artificial light (e.g. sunbeds) 17. Taking medication contra-indicated to minocycline
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The co-primary endpoints are: 1. Blood brain barrier permeability (white matter permeability) measured using MRI at baseline and 3 months 2. Microglial activation ([11C]-PK11195 binding) measured using PET of ‘hot-spots’ of binding in the white matter at baseline and 3 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 25/02/2019: 1. Volume of tissue with abnormal BBB permeability and/or neuro-inflammation at baseline and 3 months 2. Blood endothelial and inflammatory markers (CRP, ICAM1, MMP9, thrombomodulin) at baseline and 3 months 3. Cognitive outcome measures at baseline and 12 months: 3.1. Working Memory (WM), measured using digit span 3.2. Episodic (Long Term) Memory (LTM), measured using logical memory I & II and visual reproduction I & II from the WMS-IV battery 3.3. Processing Speed (PS), measured using digit symbol substitution, B-MIPB speed of information processing task, and the grooved pegboard task 3.4. Executive Function (EF), measured using trail-making test (part B), single letter (FAS) verbal fluency, and the Wisconsin card sort test 3.5 Mood assessment (Apathy and Depression) measured using the Geriatric Depression Scale (Long Form, GDS-30) Previous secondary outcome measures: 1. Volume of tissue with abnormal BBB permeability and/or neuro-inflammation at baseline and 3 months 2. Blood endothelial and inflammatory markers (CRP, ICAM1, MMP9, thrombomodulin) at baseline and 3 months 3. Cognitive outcome measures at baseline, 3 months and 12 months: 3.1. Working Memory (WM), measured using digit span 3.2. Episodic (Long Term) Memory (LTM), measured using logical memory I & II and visual reproduction I & II from the WMS-IV battery 3.3. Processing Speed (PS), measured using digit symbol substitution, B-MIPB speed of information processing task, and the grooved pegboard task 3.4. Executive Function (EF), measured using trail-making test (part B), single letter (FAS) verbal fluency, and the Wisconsin card sort test | — |
Countries
England, United Kingdom
Outcome results
None listed