- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01610089
Nitric Oxide Flux and Ureagenesis in Argininosuccinate Synthetase Deficiency (ASSD)(Citrullinemia I) (NOASSD)
RDCRN 5110, Nitric Oxide Flux and Ureagenesis in Argininosuccinate Synthetase Deficiency (ASSD)(Citrullinemia I)(Version 24Feb12, NIH Approved 4/5/2012)
Study Overview
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Texas
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Houston, Texas, United States, 77030
- Baylor College of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Participants must be adults (18 years and older) with confirmed diagnosis of Argininosuccinate Synthetase Deficiency (ASSD) (Citrullinemia I) who are able to perform study procedures.
- Diagnosis of citrullinemia I must be confirmed by a >10 fold elevation of citrulline in plasma and/or decreased AS enzyme activity in cultured skin fibroblasts or other appropriate tissue and/or identification of pathogenic mutation in the AS gene.
- Subject must be able to take oral or G-tube medication and have a history of adequate compliance of diet and treatment.
- If a woman of child bearing potential and sexually active, participant agrees to use an acceptable method of birth control.
- Most recent serum creatinine level must be less than or equal to 1.5 mg/dl. Serum creatinine measurement may be performed at the subject's local laboratory, but must have been obtained within one year of enrollment.
- Participant agrees to travel to Baylor College of Medicine for the study.
- Control subjects must be over eighteen years of age with no chronic or acute health issues.
Exclusion Criteria:
- Pregnancy, current acute illness and current hyperammonemic episode.
Study Plan
How is the study designed?
Design Details
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: stable isotope infusion
Infusion of isotopes [15N2-ureido] arginine, [5-13C,4, 4, 5, 5-D4] citrulline, [15N]citrulline, 15N sodium nitrate and [15N][18O3] potassium nitrate,[18O][13C]urea.
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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).
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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
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Endpoint data to be collected include measurement of isotopic enrichments drawn at 0, 6, 7 and 7.5 hours of infusion.
Measurements will include urea, carbon-arginine, guanido-arginine, citrulline, nitric oxide, nitrate and 15N-nitrate.
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0, 6, 7 and 7.5 hours of infusion
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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Endpoint data to be collected include measurement of isotopic enrichments drawn at 0, 6, 7 and 7.5 hours of infusion.
Measurements will include urea, carbon-arginine, guanido-arginine, citrulline, nitric oxide, nitrate and 15N-nitrate.
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0, 6, 7 and 7.5 hours of infusion
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Brendan Lee, MD, PhD, Baylor College of Medicine
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- H-27226
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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