Carbidopa for the treatment of nausea and vomiting in familial dysautonomiaIND #

卡比多巴用于治疗家族性自主神经功能障碍患者的恶心和呕吐IND

• 批准号: 7937709
• 负责人: HORACIO KAUFMANN
• 金额: $ 16.71万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-23 至 2011-09-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7937709
• 关键词: Carbidopa; treatment; nausea; vomiting; familial

DESCRIPTION (provided by applicant): This is a pilot clinical trial of carbidopa to treat the disabling attacks of nausea and vomiting suffered by patients with FD (also known as Riley Day syndrome or hereditary sensory and autonomic neuropathy type III). Familial dysautonomia is a rare autosomal recessive disease in which the growth and development of selective neuronal populations is impaired. Patients with FD suffer recurrent uncontrollable nausea and vomiting accompanied by skin flushing, tachycardia and arterial hypertension. Current treatments of nausea and vomiting are ineffective or have intolerable side sides. The investigators have recently found that resting plasma dopamine levels are high in patients with FD and increase up to 40-fold during nausea and vomiting attacks. They indicate that this strongly suggests that stimulation of dopamine receptors in the chemoreceptor trigger zone of the brainstem is the likely mechanism of vomiting. Carbidopa is a reversible competitive inhibitor of aromatic L-amino acid decarboxylase (also known as dopa-decarboxylase) that does not cross the blood brain barrier. Carbidopa has been used successfully for many years to block the extracerebral synthesis of dopamine and avoid nausea and vomiting in patients with Parkinson's disease taking levodopa. The investigators reason that carbidopa could have a similar antiemetic effect in patients with FD. The investigators will conduct a pilot trial to assess the safety, tolerability and efficacy of carbidopa for the treatment of nausea and vomiting in patients with FD. Twenty-five patients with FD who complain of severe nausea that affects their quality of life will participate in this trial. The trial will be divided into two consecutive, but independent parts. Part 1 will address the safety and tolerability of carbidopa in patients with FD using an open-label dose titration phase followed by 4-weeks of open-label treatment. Part 2 will address the efficacy of carbidopa for the treatment of nausea in patients with FD using a randomized, placebo controlled, double blind, 4-week cross over design. The investigators hope to demonstrate that carbidopa is a safe, well-tolerated drug that blocks the peripheral formation of dopamine and thus prevents dopamine-induced nausea and vomiting attacks in patients with FD. Their long-term goal is to treat nausea effectively and without side effects, a therapeutic intervention that will markedly improve the quality of life of patients with FD.

描述（由申请人提供）： 这是卡比多巴的一项试点临床试验，用于治疗 FD（也称为 Riley Day 综合征或 III 型遗传性感觉和自主神经病）患者所遭受的恶心和呕吐致残性发作。 家族性自主神经功能障碍是一种罕见的常染色体隐性遗传疾病，其中选择性神经元群的生长和发育受到损害。 FD 患者反复出现无法控制的恶心和呕吐，并伴有皮肤潮红、心动过速和动脉高压。目前对恶心和呕吐的治疗无效或有难以忍受的副作用。 研究人员最近发现，FD 患者的静息血浆多巴胺水平很高，并且在恶心和呕吐发作时会增加高达 40 倍。他们指出，这强烈表明刺激脑干化学感受器触发区的多巴胺受体是呕吐的可能机制。 卡比多巴是芳香族L-氨基酸脱羧酶（也称为多巴脱羧酶）的可逆竞争性抑制剂，不能穿过血脑屏障。卡比多巴多年来已成功用于阻断多巴胺的脑外合成，并避免服用左旋多巴的帕金森病患者出现恶心和呕吐。 研究人员推断卡比多巴对 FD 患者可能具有类似的止吐作用。 研究人员将进行一项试点试验，以评估卡比多巴治疗 FD 患者恶心和呕吐的安全性、耐受性和有效性。 25 名抱怨严重恶心影响生活质量的 FD 患者将参加这项试验。审判将分为两个连续但独立的部分。第 1 部分将讨论卡比多巴在 FD 患者中的安全性和耐受性，使用开放标签剂量滴定阶段，然后进行 4 周的开放标签治疗。第 2 部分将采用随机、安慰剂对照、双盲、4 周交叉设计探讨卡比多巴治疗 FD 患者恶心的疗效。 研究人员希望证明卡比多巴是一种安全、耐受性良好的药物，可以阻断外周多巴胺的形成，从而预防 FD 患者因多巴胺引起的恶心和呕吐。他们的长期目标是有效治疗恶心且无副作用，这种治疗干预措施将显着改善 FD 患者的生活质量。