NCT01610089

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

RDCRN 5110, Nitric Oxide Flux and Ureagenesis in Argininosuccinate Synthetase Deficiency (ASSD)(Citrullinemia I)(Version 24Feb12, NIH Approved 4/5/2012)

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: Baylor College of Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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 description

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.

Conditions

• Citrullinemia

Interventions

Type	Name	Description
OTHER	stable isotope infusion	Control subjects: \[15N2-ureido\] arginine (0.69 mg/kg); \[5-13C,4,4,5,5-D4\] citrulline (0.18mg/kg); 15N citrulline (0.03mg/kg); 15N sodium nitrate (0.003 mg/kg), \[15N\]\[18O3\] potassium nitrate (0.03 mg/kg) and \[18O\]\[13C\]urea (1 mg/kg)over 10 minutes. Followed by a 8-hour infusion of \[15N2-ureido\] arginine (0.69 mg/kg/hr); \[5-13C,4,4,5,5-D4\] citrulline (0.18mg/kg/hr), \[15N\]\[18O3\] potassium nitrate (0.003 mg/kg/hr) and \[18O\]\[13C\]urea (0.1 mg/kg/hr). Citrullinemia type 1 subjects,\[15N2-ureido\] arginine (4.14 mg/kg); \[5-13C,4,4,5,5-D4\] citrulline (1.08 mg/kg); 15N citrulline (0.18mg/kg); 15N sodium nitrate (0.003 mg/kg), \[15N\]\[18O3\] potassium nitrate (0.03 mg/kg) and \[18O\]\[13C\]urea (1 mg/kg)over 10 minutes, followed by a 8-hour infusion of \[15N2-ureido\] arginine (4.14 mg/kg/hr); \[5-13C,4,4,5,5-D4\] citrulline (1.08 mg/kg/hr), \[15N\]\[18O3\] potassium nitrate (0.003 mg/kg/hr) and \[18O\]\[13C\]urea (0.1 mg/kg/hr).

Timeline

• Start date: 2012-12-01
• Primary completion: 2013-09-01
• Completion: 2013-09-01
• First posted: 2012-06-01
• Last updated: 2015-03-20

Locations

1 site across 1 country: United States