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Trials
Published in: Trials 1/2023

Open Access 01-12-2023 | Minocycline | Study protocol

Minocycline for sporadic and hereditary cerebral amyloid angiopathy (BATMAN): study protocol for a placebo-controlled randomized double-blind trial

Authors: S. Voigt, E. A. Koemans, I. Rasing, E. S. van Etten, G. M. Terwindt, F. Baas, K. Kaushik, A. C. G. M. van Es, M. A. van Buchem, M. J. P. van Osch, M. A. A. van Walderveen, C. J. M. Klijn, M. M. Verbeek, L. van der Weerd, M. J. H. Wermer

Published in: Trials | Issue 1/2023

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Abstract

Background

Cerebral amyloid angiopathy (CAA) is a disease caused by the accumulation of the amyloid-beta protein and is a major cause of intracerebral hemorrhage (ICH) and vascular dementia in the elderly. The presence of the amyloid-beta protein in the vessel wall may induce a chronic state of cerebral inflammation by activating astrocytes, microglia, and pro-inflammatory substances. Minocycline, an antibiotic of the tetracycline family, is known to modulate inflammation, gelatinase activity, and angiogenesis. These processes are suggested to be key mechanisms in CAA pathology. Our aim is to show the target engagement of minocycline and investigate in a double-blind placebo-controlled randomized clinical trial whether treatment with minocycline for 3 months can decrease markers of neuroinflammation and of the gelatinase pathway in cerebrospinal fluid (CSF) in CAA patients.

Methods

The BATMAN study population consists of 60 persons: 30 persons with hereditary Dutch type CAA (D-CAA) and 30 persons with sporadic CAA. They will be randomized for either placebo or minocycline (15 sporadic CAA/15 D-CAA minocycline, 15 sporadic CAA/15 D-CAA placebo). At t = 0 and t = 3 months, we will collect CSF and blood samples, perform a 7-T MRI, and collect demographic characteristics.

Discussion

The results of this proof-of-principle study will be used to assess the potential of target engagement of minocycline for CAA. Therefore, our primary outcome measures are markers of neuroinflammation (IL-6, MCP-1, and IBA-1) and of the gelatinase pathway (MMP2/9 and VEGF) in CSF. Secondly, we will look at the progression of hemorrhagic markers on 7-T MRI before and after treatment and investigate serum biomarkers.

Trial registration

ClinicalTrials.gov NCT05680389. Registered on January 11, 2023
Appendix
Available only for authorised users
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Metadata
Title
Minocycline for sporadic and hereditary cerebral amyloid angiopathy (BATMAN): study protocol for a placebo-controlled randomized double-blind trial
Authors
S. Voigt
E. A. Koemans
I. Rasing
E. S. van Etten
G. M. Terwindt
F. Baas
K. Kaushik
A. C. G. M. van Es
M. A. van Buchem
M. J. P. van Osch
M. A. A. van Walderveen
C. J. M. Klijn
M. M. Verbeek
L. van der Weerd
M. J. H. Wermer
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Trials / Issue 1/2023
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-023-07371-4

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