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Oxidative Stress, Inflammation and Acute Decompensation in Urea Cycle Disorders

This study has been terminated.
(DSMB suggested closure due to low enrollment)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Rare Diseases Clinical Research Network
Information provided by (Responsible Party):
Mark Batshaw, Children's Research Institute Identifier:
First received: February 8, 2012
Last updated: October 1, 2015
Last verified: October 2015
The primary purpose of the proposed study is to characterize the oxidative stress and inflammatory cytokine status in UCD during baseline and decompensated states.

Urea Cycle Disorders

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Oxidative Stress, Inflammation and Acute Decompensation in Urea Cycle Disorders

Resource links provided by NLM:

Further study details as provided by Children's Research Institute:

Primary Outcome Measures:
  • Laboratory values indicating oxidative stress [ Time Frame: Change from baseline to period of decompensation up to one year ]
    Laboratory values that indicate oxidative stress include IL-1, IL-2, IL-6, and IL-8. These values will be analyzed as a panel (not individually) comparing baseline values to values during periods of decompensation.

Enrollment: 10
Study Start Date: February 2012
Study Completion Date: July 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Detailed Description:

Protein turnover is a cyclic process with a net loss of protein in the fasting state and a net gain in the fed state contributing to nitrogen balance. These physiologic processes are impacted during infection; whole-body protein catabolism exceeds protein synthesis, resulting in net loss of whole-body protein. Patients with urea cycle disorders suffer episodes of periodic hyperammonemic crisis, often in association with intercurrent infections. The immediate cause of this decompensation is the increase in endogenous protein catabolism that is the endpoint of a cascade triggered by intercurrent illness. This increase in protein catabolism leads to elevations of serum amino acids and ammonia production, which cannot be eliminated by a dysfunctional urea cycle.

It is well known that infectious illnesses play a significant role in precipitating metabolic crises in urea cycle defects, presumably by triggering a cascade of events involving the release of inflammatory cytokines that lead to increased protein catabolism. Cytokines have also been implicated as distant mediators of oxidative stress. However, the correlation between oxidative stress, cytokine levels, and severity of a crisis is currently unclear.

The primary purpose of the proposed study is to characterize the oxidative stress and inflammatory cytokine status in UCD during baseline and decompensated states. The investigators will undertake measurements of selected markers of oxidative stress and cytokines in serum and urine during baseline and decompensated states in subjects with UCD in order to establish their prognostic value as biomarkers for disease severity and/or predictors of metabolic decompensation.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Urea cycle disorders Inherited metabolic disorders N-acetylglutamate synthase (NAGS) deficiency Carbamyl phosphate synthetase I (CPSI) deficiency Ornithine transcarbamylase (OTC) deficiency Argininosuccinate synthetase (AS) deficiency (Citrullinemia) Argininosuccinate lyase (AL) deficiency (argininosuccinic aciduria Arginase (ARG) deficiency (hyperargininemia) Hyperornithinemia, hyperammonemia and homocitrullinuria (HHH) syndrome, or mitochondrial ornithine carrier (ORNT) deficiency Citrullinemia type II, mitochondrial aspartate/glutamate carrier (CITR) deficiency

Inclusion Criteria:

  • Confirmed or highly-likely diagnosis of one of the eight UCDs as established for the Longitudinal Study (5101) (See section 4.2 Inclusion Criteria, Table 4 for diagnostic criteria for patients with UCD)
  • Enrolled in Longitudinal Study of Urea Cycle Disorders (RDCRN UCDC #5101)

Exclusion Criteria:

  • UCD patients who have undergone orthotopic liver transplantation
  • Significant chronic medical co-morbidity that might confound the analysis as determined by the site investigators.
  • Significant co-morbidities include but are not limited to:

    • diabetes, liver failure + cirrhosis
    • renal failure
    • cardiac disease
    • chronic inflammatory diseases
    • asthma requiring daily long-term control medications
    • significant respiratory disease.
  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 identifier: NCT01541722

United States, California
University of California, Los Angeles
Los Angeles, California, United States, 90095
United States, Colorado
The Children's Hospital, Aurora
Aurora, Colorado, United States, 80045
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Ohio
Case Western Medical College
Cleveland, Ohio, United States, 44106
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Children's Hospital and Regional Medical Center
Seattle, Washington, United States, 98105
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
Mark Batshaw
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Rare Diseases Clinical Research Network
Principal Investigator: George Diaz Icahn School of Medicine at Mount Sinai
  More Information

Additional Information:
Responsible Party: Mark Batshaw, MD, Children's Research Institute Identifier: NCT01541722     History of Changes
Other Study ID Numbers: RDCRN 5109
U54HD061221 ( US NIH Grant/Contract Award Number )
Study First Received: February 8, 2012
Last Updated: October 1, 2015

Keywords provided by Children's Research Institute:
Urea cycle disorders

Additional relevant MeSH terms:
Urea Cycle Disorders, Inborn
Pathologic Processes
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases processed this record on April 28, 2017