肾上腺髓质素治疗大脑常染色体显性动脉病伴有皮层下梗死和白质脑病患者的多中心、单臂、II 期临床试验

IF 1.9 Q3 CLINICAL NEUROLOGY Cerebral circulation - cognition and behavior Pub Date : 2024-01-01 DOI:10.1016/j.cccb.2024.100211

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

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引用次数: 0

摘要

背景大脑常染色体显性动脉病伴有皮层下梗塞和白质脑病（CADASIL）是遗传性脑小血管病（SVD）中最常见的一种，目前缺乏改变病情的治疗方法。肾上腺髓质素（AM）是一种血管活性肽，具有血管生成、血管扩张、抗炎和抗氧化特性，对神经胶质血管单元具有潜在作用。AMCAD研究旨在评估AM对CADASIL患者的疗效和安全性。根据 NOTCH3 基因检测确诊为 CADASIL 的患者将在基线评估（第 1 天至第 14 天）后接受为期 14 天的 8 小时 AM 治疗（15 纳克/千克/分钟）。随访评估将在第 15、28、90 和 180 天进行。研究结果主要终点是额叶皮层的脑血流变化率，使用动脉自旋标记磁共振成像进行评估，时间从基线到第 28 天。分析将采用汇总统计、95% 置信区间和单样本t检验。结论AMCAD研究旨在体现AM对CADASIL患者的治疗潜力，满足这一具有挑战性的疾病尚未得到满足的医疗需求。临床试验注册jRCT 2,051,210,117 (https://jrct.niph.go.jp/en-latest-detail/jRCT2051210117)。

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

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.