Clinical Trial: The NIH UNI Study: Urea Cycle Disorders, Nutrition and Immunity

Study Status: Terminated
Recruit Status: Terminated
Study Type: Observational

Official Title: The NIH UNI Study: Urea Cycle Disorders, Nutrition and Immunity

Brief Summary:

Objectives:

  • To study nutrition and immune system problems in people with urea cycle disorders.
  • To study how people with urea cycle disorders and healthy volunteers respond to standard flu and/or hepatitis A vaccines.
  • To compare differences in nutrition and immune systems of people with urea cycle disorders with that of healthy volunteers.

Eligibility:

  • Healthy males and females at least 2 years of age who are able to travel to the National Institutes of Health hospital in Bethesda, MD
  • Males and females at least 2 years of age who have a urea cycle disorder and are able to travel to the National Institutes of Health hospital in Bethesda, MD.

Design:

For Patients with urea cycle disorder:

  • Participants will spend 2 to 3 days in the National Institutes of Health hospital for the following tests:
  • A physical exam and review of medical history
  • Food log for 3 days before the start of the study
  • Blood tests
  • 24-hour urine collection
  • Resting metabolism test
  • DEXA scan imaging study of bones and body fat
  • Participants who are old enough to do certain tasks by themselves (like dressing and eating) can choose to have the following extra tests:
  • 24-hour metabol

    Detailed Summary:

    Urea cycle disorders (UCD) are amongst the most frequent of the inborn errors of metabolism (IEM) and result from a block in the hepatic disposal of waste nitrogen from protein catabolism. Viral infections play a significant role in precipitating life-threatening acute hyperammonemic crises in UCD. The recent H1N1 influenza pandemic has placed this vulnerable population at significant risk. The standard of care for these patients is routine vaccination for seasonal and H1N1 influenza viruses. However, nutritional deficiencies and their underlying enzymopathy may affect the efficacy of vaccination.

    Dietary management of urea cycle disorders includes dietary modification with protein restriction. Protein energy malnutrition, essential fatty acid deficiencies and micronutrient deficiencies due to restrictive dietary management have been reported in various inborn errors of metabolism. In general, dietary deficiencies and their effect on immune function are well documented.

    In addition to the disposal of waste nitrogen, the urea cycle also generates arginine for various biologic functions. Depending on the site of the metabolic block, UCD patients are at risk for becoming systemically deficient in citrulline and arginine, with potential implications for the immune system. The immunomodulatory roles of the amino acids citrulline and arginine have been characterized in the context of nutritional deficiencies in disease states such as cancer and sepsis. Systemic infection may also deplete systemic citrulline and arginine, compounding an underlying deficiency in UCD. Cells of the immune system have a more direct relationship with the urea cycle: urea cycle enzymes arginosuccinate synthetase (ASS), arginosuccinate lyase (ASL) and arginase (ARG1) may also be components of leukocyte metabolism. Overall, general and specific nutrition
    Sponsor: National Human Genome Research Institute (NHGRI)

    Current Primary Outcome:

    Original Primary Outcome:

    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: August 20, 2011
    Date Started: August 8, 2011
    Date Completion: April 17, 2013
    Last Updated: April 19, 2017
    Last Verified: April 17, 2013