Pharmacotoxicology of Trichloroethylene Metabolites

June 3, 2015 updated by: University of Florida
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida Shands Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years to 46 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy volunteers

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hypothesize That Subject's Genotype Will Determine How DCA is Metabolized.
Time Frame: 24 hours for analysis on Day 5, Clinical dose
Terminal half-life (the amount of time needed to clear one-half of dose of the drug).
24 hours for analysis on Day 5, Clinical dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
24 hours for analysis on Day 5, Environmental dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Florida

Investigators

  • Principal Investigator: Peter W Stacpoole, PhD, MD, University of Florida

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2009

Primary Completion (Actual)

November 1, 2012

Study Completion (Actual)

November 1, 2012

Study Registration Dates

First Submitted

April 1, 2009

First Submitted That Met QC Criteria

April 1, 2009

First Posted (Estimate)

April 2, 2009

Study Record Updates

Last Update Posted (Estimate)

June 4, 2015

Last Update Submitted That Met QC Criteria

June 3, 2015

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14617-CP-004

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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