Neurogastric electrical stimulation for treating chemotherapy-induced emesis

描述（由申请人提供）：癌症是一组以异常细胞的不受控制的生长和扩散为特征的疾病。每年有超过一百万人患癌症。大约每两个美国男性中就有一个，每三个美国女性中就有一个在他们一生中的某个时候会患上某种类型的癌症。顺铂是癌症化疗中最常用的药物之一。然而，化疗引起的严重不良事件，主要是恶心和呕吐，可能比预期寿命的未来担忧更令患者痛苦。事实上，一些患者由于严重的顺铂诱导的恶心和呕吐而选择停止潜在的治愈性治疗。 止吐药是治疗癌症患者化疗引起的恶心和呕吐的最常见干预措施。止吐治疗的基础是呕吐的神经化学控制。然而，目前对于化疗引起的呕吐，尤其是迟发性呕吐，尚无满意的治疗方法。神经胃电刺激（nGES）最近已被提出，并发现有效治疗胃轻瘫患者的恶心和呕吐。其中枢和神经机制最近已被阐明。假设nGES可有效治疗化疗诱导的呕吐。 本计画的长期目标是发展一种内视镜植入式微刺激器，用于治疗化疗引起的呕吐。该I期项目的目的是研究这种新方法治疗化疗引起的呕吐的可行性。具体目标包括顺铂诱导呕吐动物模型的可行性研究、涉及nGES的中枢和神经元机制研究以及基于作用机制的nGES治疗优化。 已成立一支有竞争力的团队，其中包括胃肠电刺激、中枢神经系统生理学和微刺激器方面的专家。公共卫生相关性：化疗引起的呕吐是癌症患者治疗中的主要问题之一，并且在使用某些药物（例如顺铂）的情况下超过90%的病例中发生。随着最近止吐药物的进步，急性呕吐得到了更好的控制;然而，延迟呕吐仍然是一个很大的挑战。本研究提出一种新的胃神经电刺激（nGES）治疗化疗所致呕吐的方法。初步的数据支持这一新的概念和实验设计，以测试所提出的方法的可行性。

DESCRIPTION (provided by applicant): Cancer is a group of diseases characterized by uncontrolled growth and spread of abnormal cells. Over one million people get cancer each year. Approximately one out of every two American men and one out of every three American women will have some type of cancer at some point during their lifetime. Cisplatin is one of the most commonly used drugs in chemotherapy for cancers. However, severe adverse events resulting from chemotherapies, mainly nausea and vomiting may be much more distressing to a patient than future concerns of life expectancy. In fact, some patients choose to discontinue potentially curative therapy because of severe Cisplatin-induced nausea and vomiting. Antiemetic agents are the most common intervention in the management of chemotherapy-induced nausea and vomiting in cancer patients. The basis for antiemetic therapy is the neurochemical control of vomiting. However, currently, there are no satisfactory therapies for treating chemotherapy-induced emesis, especially delayed emesis. Neurogastric electrical stimulation (nGES) has recently been proposed and found effective in treating nausea and vomiting in patients with gastroparesis. Its central and neuronal mechanisms have recently been elucidated. It is hypothesized that nGES is effective in treating chemotherapy-induced emesis. The long-term aim of this project is to develop an endoscopically implantable microstimulator for the treatment of chemotherapy-induced emesis. The aim of this Phase I project is to study the feasibility of this novel method for treating chemotherapy- induced emesis. Specific objectives include a feasibility study in an animal model of Cisplatin-induced emesis, central and neuronal mechanistic studies involving nGES and optimization of the nGES therapy based on the mechanisms of action. A competitive team has been established, including experts in gastrointestinal electrical stimulation, physiology of the central nervous system and micro-stimulators. PUBLIC HEALTH RELEVANCE: Chemotherapy-induced emesis is one of major problems in the treatment of patients with cancer and occurs in more than 90% of cases with certain medications, such as Cisplatin. With the recent advancement of anti-emetic medications, acute emesis is better controlled; however, delayed emesis remains a big challenge. A novel method of neurogastric electrical stimulation (nGES) is proposed in this project for the treatment of chemotherapy-induced emesis. Preliminary data supports this novel concept and experiments are designed to test the feasibility of the proposed method.