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. 2024 Feb 6:6:100211.
doi: 10.1016/j.cccb.2024.100211. eCollection 2024.

A multicenter, single-arm, phase II clinical trial of adrenomedullin in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Kazuo Washida  1 , Satoshi Saito  1 , Tomotaka Tanaka  1 , Yuriko Nakaoku  2 , Hiroyuki Ishiyama  1 , Soichiro Abe  1 , Takehito Kuroda  1 , Shinsaku Nakazawa  1 , Chikage Kakuta  1 , Katsuhiro Omae  3 , Kenta Tanaka  3 , Manabu Minami  3 , Yoshiaki Morita  4 , Tetsuya Fukuda  4 , Akihiro Shindo  5 , Takakuni Maki  6 , Kazuo Kitamura  7 , Hidekazu Tomimoto  5 , Toshihiko Aso  8 , Masafumi Ihara  1
Affiliations

A multicenter, single-arm, phase II clinical trial of adrenomedullin in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Kazuo Washida et al. Cereb Circ Cogn Behav. .

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 NOTCH3 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 t-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).

Keywords: Adrenomedullin; Arterial spin labeling; Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; Cerebral blood flow; Clinical trial.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare that Kitamura K. own stock in Himuka AM Pharma Corporation, a company aiming to develop adrenomedullin and its derivatives as a novel drug.

Figures

Fig 1
Fig. 1
The schedule of interventions and assessments in the AMCAD study. Abbreviations: AM, Adrenomedullin; DTI, Diffusion tensor imaging; SPECT, Single photon emission computed tomography.
See this image and copyright information in PMC

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References

    1. Chabriat H., Joutel A., Dichgans M., Tournier-Lasserve E., Bousser MG. Cadasil. Lancet Neurol. 2009;8(7):643–653. doi: 10.1016/s1474-4422(09)70127-9. - DOI - PubMed
    1. Rajani R.M., Ratelade J., Domenga-Denier V., et al. Blood brain barrier leakage is not a consistent feature of white matter lesions in CADASIL. Acta Neuropathol. Commun. 2019;7(1):187. doi: 10.1186/s40478-019-0844-x. - DOI - PMC - PubMed
    1. Wang R., Zhang J., Shang J., Wang F., Yan X. Effects of different regional cerebral blood flow on white matter hyperintensity in CADASIL patients. J. Biomed. Res. 2022;36(5):368–374. doi: 10.7555/jbr.36.20220006. - DOI - PMC - PubMed
    1. Zaucker A., Mercurio S., Sternheim N., Talbot W.S., Marlow F.L. notch3 is essential for oligodendrocyte development and vascular integrity in zebrafish. Dis. Model Mech. 2013;6(5):1246–1259. doi: 10.1242/dmm.012005. - DOI - PMC - PubMed
    1. Kitamura K., Kangawa K., Kawamoto M., et al. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem. Biophys. Res. Commun. 1993;192(2):553–560. doi: 10.1006/bbrc.1993.1451. - DOI - PubMed