Switching off leakage and inflammation in small brain blood vessels

Not Applicable

Completed

• Conditions: Cerebral small vessel disease; Circulatory System; Stroke, not specified as haemorrhage or infarction

• Registration Number: ISRCTN15483452
• Lead Sponsor: Cambridge University Hospitals NHS Foundation Trust

Brief Summary

2022 Protocol article in https://pubmed.ncbi.nlm.nih.gov/36082255/ (added 29/11/2022) 2024 Results article in https://pubmed.ncbi.nlm.nih.gov/38629936/ (added 18/04/2024)

Detailed Description

Not available

Study Timeline

• Study Start: 2018-10-01
• Study Completion: 2023-06-30
• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 48

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

Current exclusion criteria as of 21/11/2019:
1. Unable/unwilling to consent
2. MMSE <21 (for consent issues)
3. Age <18 years
4. Lacunar infarcts >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)1.154 x (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:
11.1. Allergic to minocycline hydrochloride or other similar antibiotics
11.2. Have had complete kidney failure
11.3. Suffer from myasthenia gravis, have impaired liver or kidney function or have systemic lupus erythematosus (SLE)
11.4. Suffer from increased pressure in the skull
11.5. Are sensitive to sunlight or artificial light (e.g. sunbeds)
12. Taking medication contra-indicated to minocycline

Previous exclusion criteria:
1. Unable/unwilling to consent
2. MMSE <21 (for consent issues)
3. Age <18 years
4. Lacunar infarcts >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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The co-primary endpoints are:<br>1. Blood brain barrier permeability (white matter permeability) measured using MRI at baseline and 3 months<br>2. Microglial activation ([11C]-PK11195 binding) measured using PET of ‘hot-spots’ of binding in the white matter at baseline and 3 months