Journal Article Epublish 2 citations
PubMed: 38375188 DOI: 10.1016/j.cccb.2024.100211
A multicenter, single-arm, phase II clinical trial of adrenomedullin in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
Cereb Circ Cogn Behav 6:100211
Authors: Kazuo Washida, Satoshi Saito, Tomotaka Tanaka, Yuriko Nakaoku, Hiroyuki Ishiyama, Soichiro Abe, Takehito Kuroda, Shinsaku Nakazawa, Chikage Kakuta, Katsuhiro Omae, Kenta Tanaka, Manabu Minami, Yoshiaki Morita, Tetsuya Fukuda, Akihiro Shindo, Takakuni Maki, Kazuo Kitamura, Hidekazu Tomimoto, Toshihiko Aso, Masafumi Ihara
Affiliations
- Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.
- Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center, Suita, Japan.
- Department of Data Science, National Cerebral and Cardiovascular Center, Suita, Japan.
- Department of Radiology, National Cerebral and Cardiovascular Center, Suita, Japan.
- Department of Neurology, Mie University Graduate school of Medicine, Tsu, Japan.
- Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
- Department of Projects Research, Frontier Science Research Center, University of Miyazaki, Miyazaki, Japan.
- Laboratory for Brain Connectomics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
Abstract
Background
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of hereditary cerebral small vessel disease (SVD), currently lacks disease-modifying treatments. Adrenomedullin (AM), a vasoactive peptide with angiogenic, vasodilatory, anti-inflammatory, and anti-oxidative properties, shows potential effects on the neuro-glial-vascular unit.
Objective
The AdrenoMedullin for CADASIL (AMCAD) study aims to assess the efficacy and safety of AM in patients with CADASIL.
Sample size
Overall, 60 patients will be recruited.
Methods
The AMCAD is a multicenter, investigator-initiated, single-arm phase II trial. Patients with a confirmed CADASIL diagnosis, based on genetic testing, will receive an 8-h AM treatment (15 ng/kg/min) for 14 days following a baseline assessment (from day 1 to day 14). Follow-up evaluations will be performed on days 15, 28, 90, and 180.
Study outcomes
The primary endpoint is the cerebral blood flow change rate in the frontal cortex, evaluated using arterial spin labeling magnetic resonance imaging, from baseline to day 28. Summary statistics, 95% confidence intervals, and a one-sample -test will be used for analysis.
Conclusion
The AMCAD study aims to represent the therapeutic potential of AM in patients with CADASIL, addressing an unmet medical need in this challenging condition.
Clinical Trial Registration
jRCT 2,051,210,117 (https://jrct.niph.go.jp/en-latest-detail/jRCT2051210117).
MeSH
Genetic Testing, Therapeutics, Leukoencephalopathies, Cadasil, Adrenomedullin