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.
Pilot projects are a means of testing out hypotheses rapidly and at little cost to see if they should be further pursued. The three initial projects span the range of goals for the UCDC. One focuses on early diagnosis, which is essential for a good outcome;a second performs a treatment trial of a new therapeutic intervention;and the third allows patients and families to provide input to investigators about outcomes through a registry.
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