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

Trials

Study Protocol

F. Baas¹  C. J. M. Klijn²  M. M. Verbeek²  K. Kaushik³  E. A. Koemans³  M. J. H. Wermer³  E. S. van Etten³  I. Rasing³  G. M. Terwindt³  S. Voigt⁴  M. A. A. van Walderveen⁵  A. C. G. M. van Es⁵  M. J. P. van Osch⁵  M. A. van Buchem⁵  L. van der Weerd⁵ 

[1]Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands

[2]Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands

[3]Department of Neurology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands

[4]Department of Neurology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands

[5]Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands

[6]Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands

关键词: Cerebral amyloid angiopathy;    Minocycline;    Dutch-type CAA;    Cerebrospinal fluid;    7T MRI;    Randomized controlled trial;   

DOI  :  10.1186/s13063-023-07371-4

 received in 2023-03-06, accepted in 2023-05-11,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundCerebral 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.MethodsThe 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.DiscussionThe 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 registrationClinicalTrials.gov NCT05680389. Registered on January 11, 2023

【 授权许可】

CC BY   
© The Author(s) 2023

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