A Multicenter, Single-arm, Phase II Clinical Trial of Adrenomedullin in Patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

Overview

Journal Cereb Circ Cogn Behav

Date 2024 Feb 20

PMID 38375188

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

Soon will be listed here.

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).

Citing Articles

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Yoshimoto T, Saito S, Omae K, Tanaka K, Kita T, Kitamura K EClinicalMedicine. 2024; 77:102901.

PMID: 39618942 PMC: 11605132. DOI: 10.1016/j.eclinm.2024.102901.

The Role of Adrenomedullin as a Predictive Marker of the Risk of Death and Adverse Clinical Events: A Review of the Literature.

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