Pilot/Demonstration Clinical Research Projects Program

UCDC试点/示范临床研究项目的主要目的是为创新想法或假设的研究提供资金，如果成功，最终可能导致UCD的预防、诊断和/或治疗的改进。我们提出了三个试点项目，这些项目是从UCDC调查员响应我们的内部RFA提交的13个项目中选出的，还有一个是从DMCC提交的。第一个项目将进行一项小型双盲安慰剂对照临床试验，研究药物（乙酰羟肟酸）旨在阻断肠道菌群中的脲酶活性，目的是减少肠道氨生成，以减少近端UCD患者的氨负荷。第二个项目建议开发NEXTGEN测序方法，以识别三种近端UCD （NAGSD, CPSI D， OTCD）的突变，长期目标是将该方法用作扩大新生儿筛查这些疾病的二级测试。第三个项目建议扩大UCDC目前的接触者登记，使用PROMISE网站从注册者那里获得尿素循环相关体征和症状的患者报告结果，验证治疗设置的数据，并评估UCDC项目十年来治疗的变化。

The principal aim of the UCDC pilot/demonstration clinical research program is to provide funding for studies of innovative ideas or hypotheses which, if successful, could ultimately lead to improvement in the prevention, diagnosis and/or treatment of UCD. We propose three pilot projects that were selected from 13 projects submitted in response to our internal RFA by UCDC investigators and one from the DMCC. The first project will conduct a small double blind placebo controlled clinical trial of an investigational drug (acetohydroxamic acid) aimed to block urease activity in the intestinal flora, with the goal of reducing intestinal ammonia production to reduce ammonia load in patients with proximal UCD. The second project proposes to develop a NEXTGEN sequencing methods to identify mutations in the three proximal UCD (NAGSD, CPSI D, OTCD) with the long-term goal of using this method as a second-tier test for expanded newborn screening for these disorders. The third project proposes to expand the current contact registry of the UCDC to obtain patient reported outcomes from registrants on urea cycle relevant sign and symptoms using the PROMISE web site and validate data on treatment setting and assess changes in treatments over the ten years of the UCDC program.