Pharmacotoxicology of Trichloroethylene Metabolites

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT00874276
First received: April 1, 2009
Last updated: May 9, 2013
Last verified: March 2013

April 1, 2009
May 9, 2013
August 2009
November 2012   (final data collection date for primary outcome measure)
Hypothesize That Subject's Genotype Will Determine How DCA is Metabolized. [ Time Frame: 24 hours for analysis on Day 5, Clinical dose ] [ Designated as safety issue: No ]
Terminal half-life (the amount of time needed to clear one-half of dose of the drug).
Hypothesize that the log half-life of CH or DCA will increase ≥ 2-fold from day 1 - day 5 for each treatment. [ Time Frame: August, 2009 - February, 2011 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00874276 on ClinicalTrials.gov Archive Site
Terminal Half-life (the Amount of Time Needed to Clear One-half of the Dose of Drug)for Environmental Dose 2.5 ug/kg/Day. [ Time Frame: 24 hours for analysis on Day 5, Environmental dose ] [ Designated as safety issue: No ]
Terminal half-life (the amount of time needed to clear one-half of the dose of drug)for the environmental dose 2.5 ug/kg/day.
Not Provided
Not Provided
Not Provided
 
Pharmacotoxicology of Trichloroethylene Metabolites
Pharmacotoxicology of Trichloroethylene Metabolites

To establish the relationship between human MAAI haplotype and DCA and tyrosine metabolism. This aim test the postulates that MAAI haplotype determines, and thus can predict,1) dose-dependent DCA kinetics and biotransformation.

The arms of the study involves determining the haplotype of individuals enrolled. Then participants were divided into two groups based on their genotype. The groups include a genotype with an EGT alle and a group of genotype without an EGT alle. All subjects first took a low dose of DCA 2.5ug/kg for 5 days then wait 30 days and take a therapeutic dose of DCA 25mg/kg for 5 days On the first day and on the 5th day of taking DCA kinetics were be done. A total of 16 blood samples were obtained through an intravenous catheter. Urine collection will also occur.

Population pharmacogenetic analysis of MAI allelic frequencies and the GC or LC-MS/MS techniques for blood or urinary metabolites were used in this investigation. Pharmacokinetic data was used to determine metabolism rate of DCA for each allele

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Congenital Lactic Acidosis
  • Drug: Dichloroacetate (DCA)
    Dichloroacetate 2.5.ug/kg will be administered for five days in the clinical research center. On day 5 with the dose of DCA a pharmacokinetics test will be performed for 24 hours. 30 days later the individuals will return to the clinic and receive Dichloroacetate 25mg/kg (clinical dose) for five days. On day 1 and day 5 Pharmacokinetics will be performed to determine the relationship between DCA metabolism and haplotype.
    Other Names:
    • genotype
    • Dichloroacetate (DCA)
  • Genetic: Genetic Marker on Chromosome 14q24.3
    Individuals were genotyped at the beginning of the study and their haplotypes were defined. The study is looking at individuals with genetic markers on Chromosome 14q24.3 to determine if there will be a difference in how the DCA will be metabolized.
    Other Names:
    • Genetic Marker
    • Haplotypes
  • Experimental: No EGT Allele, slow metabolizers for DCA
    Individuals were genotyped at the beginning of the study and their haplotypes were defined. Dichloroacetate 2.5.ug/kg (non-clinical dose) will be administered for five days in the clinical research center. On day 5 with the dose of DCA a pharmacokinetics test will be performed for 24 hours. 30 days later the individuals will return to the clinic and receive Dichloroacetate 25mg/kg (clinical dose) for five days. On day 1 and day 5 Pharmacokinetics will be performed to determine the relationship between DCA metabolism and haplotype.
    Interventions:
    • Drug: Dichloroacetate (DCA)
    • Genetic: Genetic Marker on Chromosome 14q24.3
  • Experimental: 1+ EGT Allele, fast metabolizers for DCA
    Individuals were genotyped at the beginning of the study and their haplotypes were defined. Dichloroacetate 2.5.ug/kg (non-clinical dose) will be administered for five days in the clinical research center. On day 5 with the dose of DCA a pharmacokinetics test will be performed for 24 hours. 30 days later the individuals will return to the clinic and receive Dichloroacetate 25mg/kg (clinical dose) for five days. On day 1 and day 5 Pharmacokinetics will be performed to determine the relationship between DCA metabolism and haplotype.
    Interventions:
    • Drug: Dichloroacetate (DCA)
    • Genetic: Genetic Marker on Chromosome 14q24.3
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
November 2012
November 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Healthy volunteers

Exclusion Criteria:

  • Pregnancy
  • Other medications
  • Psychiatric illness on meds
  • Abnormal labs
Both
21 Years to 50 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00874276
14617-CP-004
Yes
University of Florida
University of Florida
Not Provided
Principal Investigator: Peter W Stacpoole, PhD, MD University of Florida
University of Florida
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP