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）： 这是一项卡比多巴治疗FD患者（也称为Riley Day综合征或III型遗传性感觉和自主神经病变）恶心和呕吐致残发作的初步临床试验。 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体的生长和发育受损。FD患者会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。目前的恶心和呕吐治疗是无效的或有不可忍受的副作用。 研究人员最近发现，FD患者的静息血浆多巴胺水平很高，在恶心和呕吐发作期间增加高达40倍。他们指出，这有力地表明，刺激脑干化学感受器触发区的多巴胺受体可能是呕吐的机制。 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，其不穿过血脑屏障。卡比多巴多年来一直被成功地用于阻断多巴胺的脑外合成，避免服用左旋多巴的帕金森病患者恶心和呕吐。 研究人员推断卡比多巴对FD患者可能有类似的止吐作用。 研究人员将进行一项初步试验，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例主诉严重恶心影响其生活质量的FD患者将参加本试验。审判将分为两个连续但独立的部分。第1部分将采用开放标签剂量滴定期，随后进行4周开放标签治疗，探讨卡比多巴在FD患者中的安全性和耐受性。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，可以阻断多巴胺的外周形成，从而防止FD患者多巴胺诱导的恶心和呕吐发作。他们的长期目标是有效地治疗恶心，而没有副作用，这是一种治疗干预，将显着改善FD患者的生活质量。