Clinical Trial: Nitric Oxide Flux and Ureagenesis in Argininosuccinate Synthetase Deficiency (ASSD)(Citrullinemia I)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: RDCRN 5110, Nitric Oxide Flux and Ureagenesis in Argininosuccinate Synthetase Deficiency (ASSD)(Citrullinemia I)(Version 24Feb12, NIH Approved

Brief Summary: The urea cycle consists of a series of chemical reactions through which the body converts toxic waste- nitrogen into a substance called urea that can be disposed of easily. While disposal of nitrogen is the major function of the urea cycle, recent research has shown that some enzymes of the urea cycle are also important for the production of nitric oxide. Nitric oxide is an important chemical that has many functions in the human body including regulation of blood pressure. Through this study, the investigators will study the production of nitric oxide in subjects with citrullinemia type 1 by administering stable isotopes to these subjects. Stable isotopes are harmless compounds that can be used to track and measure the production of specific compounds in the human body. The overall goal of this study is to understand if citrullinemia patients have a deficiency of nitric oxide production. This knowledge may have an impact on the treatment of patients with citrullinemia.

Detailed Summary:

This is an interventional, case control study to investigate the production of nitric oxide in patients with citrullinemia type I. Through the infusion of isotopes [15N2-ureido] arginine, [5-13C,4, 4, 5, 5-D4] citrulline, [15N]citrulline, 15N sodium nitrate and [15N][18O3] potassium nitrate, the flux of citrulline and nitrate through the urea cycle pathway will be measured in conjunction with an independent measure of total plasma arginine flux. This will be informative in dissecting the contributions of de novo production of arginine vs. exogenous contribution of arginine into total body NO flux. Total body urea production will be measured by the isotopic dilution of constantly infused [18O][13C]urea. These flux measurements will be correlated with the level of residual enzyme activity and clinical phenotype in these citrullinemia patients. The investigators plan to enroll three patients with citrullinemia.

Three unaffected control subjects will also be studied.

Sponsor: Baylor College of Medicine

Current Primary Outcome: Flux of citrulline and nitrate through the urea cycle pathway will be measured in conjunction with an independent measure of total plasma arginine flux. [ Time Frame: 0, 6, 7 and 7.5 hours of infusion ]

Original Primary Outcome: Same as current

Current Secondary Outcome: Total body urea production will be measured by the isotopic dilution of constantly infused [18O][13C]urea. [ Time Frame: 0, 6, 7 and 7.5 hours of infusion ]

Original Secondary Outcome: Same as current

Information By: Baylor College of Medicine

Dates:
Date Received: May 30, 2012
Date Started: December 2012
Date Completion:
Last Updated: March 18, 2015
Last Verified: March 2015