Clinical Trial: Urease Inhibitor Drug Treatment for Urea Cycle Disorders

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Manipulating the Gut Microbiome in Urea Cycle Disorders

Brief Summary: The purpose of this study is to determine if acetohydroxamic acid (AHA) can prevent hydrolysis of urea by inhibiting the bacterial urease of gut flora of both healthy control adults as well as adults with urea cycle disorders.

Detailed Summary:
Sponsor: Nicholas Ah Mew

Current Primary Outcome:

  • Blood and urine measurements of isotopic [13C]-urea concentration [ Time Frame: Blood: 0, 30, 60, 90, 120, 180, 240 minutes on Day 1 and Day 4; Urine: 0, 240 minutes on Day 1 and Day 4 ]
    At time zero of the study, participants will be given an intravenous bolus infusion of [13C]-urea. The concentration of [13C]-urea in the body will be measured/traced throughout the duration of the study (4 hours) by collecting blood and urine samples at specified time points. Blood [13C]-urea will be measured at time points 0, 30, 60, 90, 120, 180, and 240 minutes. Urine [13C]-urea will be measured at time points 0 and 240 minutes.
  • Blood measurements of isotopic [13-CO2] concentration [ Time Frame: 0, 30, 60, 90, 120, 180, 240 minutes on Day 1 and Day 4 ]
    At time zero of the study, participants will receive an intravenous bolus infusion of [13C]-urea. The amount of metabolized [13C]-urea in the body will be measured throughout the duration of the study by collecting blood samples and analyzing them for [13CO2] concentration. Blood [13-CO2] will be measured at time points 0, 30, 60, 90, 120, 180, and 240 minutes.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Blood and urine samples measuring urea concentration [ Time Frame: Blood: 0, 30, 60, 90, 120, 180, 240 minutes on Day 1 and Day 4; Urine: 0, 240 minutes on Day 1 and Day 4 ]
    The drug under study, Lithostat, is a bacterial urease inhibitor. Throughout the study, the investigators will measure the concentration of urea in blood and urine samples to get baseline urea measurements for the participant (no study drug) and to see how drug administration affects the levels of blood urea concentration (study drug). Blood urea measurement will occur at time points 0, 30, 60, 90, 120, 180, and 240 minutes. Urine urea measurement will occur at time points 0 and 240 minutes.
  • Blood samples measuring ammonia concentration [ Time Frame: 0, 30, 60, 90, 120, 180, 240 minutes on Day 1 and Day 4 ]
    Participants will have ammonia levels measured at various time points throughout the study. Ammonia is produced when urea is hydrolyzed by bacterial urease. The investigators predict that the administration of Lithostat, a gut bacterial urease inhibitor, will have an effect on the concentration of blood ammonia by using this study intervention. Blood ammonia will be measured at time points 0, 30, 60, 90, 120, 180, and 240 minutes.
  • Blood plasma samples measuring glutamine concentration [ Time Frame: 0, 30, 60, 90, 120, 180, 240 minutes on Day 1 and Day 4 ]
    The new indication proposed for the drug Lithostat, is for use in patients with urea cycle disorders. Elevated blood ammonia levels in patients with urea cycle disorders usually also corresponds to elevated blood glutamine levels as well. The investigators will collect blood samples to measure glutamine concentration at specified time points. Blood glutamine will be measured at time points 0, 30, 60, 90, 120, 180, and 240 minutes.


Original Secondary Outcome: Same as current

Information By: Children's Research Institute

Dates:
Date Received: January 14, 2016
Date Started: November 2016
Date Completion: March 2019
Last Updated: August 23, 2016
Last Verified: August 2016