Trial record 1 of 169 for:    "citrullinemia" OR "Amino Acid Metabolism, Inborn Errors"
Previous Study | Return to List | Next Study

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Brendan Lee, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01610089
First received: May 30, 2012
Last updated: March 18, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention
Citrullinemia
Other: stable isotope infusion

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: RDCRN 5110, Nitric Oxide Flux and Ureagenesis in Argininosuccinate Synthetase Deficiency (ASSD)(Citrullinemia I)(Version 24Feb12, NIH Approved 4/5/2012)

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 6
Study Start Date: December 2012
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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).

Other Name: stable isotopes

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01610089

Locations
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: Brendan Lee, MD, PhD Baylor College of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Brendan Lee, Professor, Molecular and Human Genetics, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01610089     History of Changes
Other Study ID Numbers: H-27226
Study First Received: May 30, 2012
Last Updated: March 18, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
citrullinemia
argininosuccinate synthetase deficiency
nitric oxide
urea

Additional relevant MeSH terms:
Citrullinemia
Amino Acid Metabolism, Inborn Errors
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Urea Cycle Disorders, Inborn
Nitric Oxide
Anti-Asthmatic Agents
Antioxidants
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Endothelium-Dependent Relaxing Factors
Free Radical Scavengers
Gasotransmitters
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on July 30, 2015