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
  Purpose

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.


Condition Intervention
Congenital Lactic Acidosis
Drug: Dichloroacetate (DCA)
Genetic: Genetic Marker on Chromosome 14q24.3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Pharmacotoxicology of Trichloroethylene Metabolites

Further study details as provided by University of Florida:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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.


Enrollment: 21
Study Start Date: August 2009
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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: 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.
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

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   21 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy volunteers

Exclusion Criteria:

  • Pregnancy
  • Other medications
  • Psychiatric illness on meds
  • Abnormal labs
  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: NCT00874276

Locations
United States, Florida
University of Florida Shands Hospital
Gainesville, Florida, United States, 32610
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Peter W Stacpoole, PhD, MD University of Florida
  More Information

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT00874276     History of Changes
Obsolete Identifiers: NCT00874705
Other Study ID Numbers: 14617-CP-004
Study First Received: April 1, 2009
Results First Received: March 11, 2013
Last Updated: May 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Florida:
DCA
Dichloroacetate
Trichloroacetate

Additional relevant MeSH terms:
Acidosis, Lactic
Acidosis
Acid-Base Imbalance
Metabolic Diseases
Trichloroethylene
Anesthetics, Inhalation
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014