Abstract
INTRODUCTION
Cerebral small vessel disease (SVD) is a common cause of stroke/vascular dementia with few effective treatments. Neuroinflammation and increased blood-brain barrier (BBB) permeability may influence pathogenesis. In rodent models, minocycline reduced inflammation/BBB permeability. We determined whether minocycline had a similar effect in patients with SVD.
METHODS
MINERVA was a single-center, phase II, randomized, double-blind, placebo-controlled trial. Forty-four participants with moderate-to-severe SVD took minocycline or placebo for 3 months. Co-primary outcomes were microglial signal (determined using 11C-PK11195 positron emission tomography) and BBB permeability (using dynamic contrast-enhanced MRI).
RESULTS
Forty-four participants were recruited between September 2019 and June 2022. Minocycline had no effect on 11C-PK11195 binding (relative risk [RR] 1.01, 95% confidence interval [CI] 0.98–1.04), or BBB permeability (RR 0.97, 95% CI 0.91–1.03). Serum inflammatory markers were not affected.
DISCUSSION
11C-PK11195 binding and increased BBB permeability are present in SVD; minocycline did not reduce either process. Whether these pathophysiological mechanisms are disease-causing remains unclear.
INTERNATIONAL CLINICAL TRIALS REGISTRY PORTAL IDENTIFIER
ISRCTN15483452
Highlights
We found focal areas of increased microglial signal and increased blood-brain barrier permeability in patients with small vessel disease.
Minocycline treatment was not associated with a change in these processes measured using advanced neuroimaging.
Blood-brain barrier permeability was dynamic but MRI-derived measurements correlated well with CSF/serum albumin ratio.
Advanced neuroimaging is a feasible outcome measure for mechanistic clinical trials.
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This post is Copyright: Robin B. Brown,
Daniel J. Tozer,
Laurence Loubière,
Eric L. Harshfield,
Young T. Hong,
Tim D. Fryer,
Guy B. Williams,
Martin J. Graves,
Franklin I. Aigbirhio,
John T. O’Brien,
Hugh S. Markus | April 17, 2024