jats:secjats:titleBackground:</jats:title>jats:p Cerebral small vessel disease (SVD) is a common cause of stroke and cognitive impairment. Recent data has implicated neuroinflammation and increased blood-brain barrier (BBB) permeability in its pathogenesis, but whether such processes are causal and can be therapeutically modified is uncertain. In a rodent model of SVD, minocycline was associated with reduced white matter lesions, inflammation and BBB permeability. </jats:p></jats:sec>jats:secjats:titleAims:</jats:title>jats:p To determine whether blood-brain barrier permeability (measured using dynamic contrast-enhanced MRI) and microglial activation (measured by positron emission tomography using the radioligand jats:sup11</jats:sup>C-PK11195) can be modified in SVD. </jats:p></jats:sec>jats:secjats:titleDesign:</jats:title>jats:p Phase II randomised double blind, placebo-controlled trial of minocycline 100 mg twice daily for 3 months in 44 participants with moderate to severe SVD defined as a clinical lacunar stroke and confluent white matter hyperintensities. </jats:p></jats:sec>jats:secjats:titleOutcomes:</jats:title>jats:p Primary outcome measures are volume and intensity of focal increases of blood-brain barrier permeability and microglial activation determined using PET-MRI imaging. Secondary outcome measures include inflammatory biomarkers in serum, and change in conventional MRI markers and cognitive performance over 1 year follow up. </jats:p></jats:sec>jats:secjats:titleDiscussion:</jats:title>jats:p The MINERVA trial aims to test whether minocycline can influence novel pathological processes thought to be involved in SVD progression, and will provide insights into whether central nervous system inflammation in SVD can be therapeutically modulated. </jats:p></jats:sec>