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

描述(由申请人提供)： 这是一项卡比多巴的试验性临床试验，用于治疗功能性消化不良(也称为Riley Day综合征或遗传性感觉和自主神经病变III型)患者的无效性恶心和呕吐。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病，其选择性神经元群体的生长发育受到损害。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都是无效的，或者有无法忍受的副作用。 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，多巴胺水平会增加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。 卡比多巴是一种芳香族L氨基酸脱羧酶(又称多巴脱羧酶)的可逆竞争性抑制剂，不会越过血脑屏障。多年来，卡比多巴已成功用于阻断服用左旋多巴的帕金森病患者的脑外多巴胺合成，并避免恶心和呕吐。研究人员推断，卡比多巴对FD患者也有类似的止吐作用。 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FD患者主诉严重恶心，影响他们的生活质量，他们将参加这项试验。审判将分为两个连续但独立的部分。第一部分将讨论卡比多巴在FD患者中的安全性和耐受性，使用开放标记剂量滴定阶段，然后进行为期4周的开放标记治疗。第二部分将采用随机、安慰剂对照、双盲、4周交叉设计研究卡比多巴治疗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患者由多巴胺引起的恶心和呕吐发作。他们的长期目标是有效地治疗恶心，没有副作用，这是一种治疗干预措施，将显著提高FD患者的生活质量。

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.