Pharmacotoxicology of Trichloroethylene Metabolites

June 2, 2015 updated by: University of Florida

Pharmacotoxicology of Trichloroethylene Metabolites: Short-term Effect of DCA on in Vivo Tyrosine Catabolism and MAAI Expression

This project focuses on the kinetics, metabolism and human toxicology of dichloroacetate (DCA)and tyrosine catabolism. The hypothesis is that tyrosine metabolism will be greatest in subject who harbor the KRT variant for GSTz1/MAAI for which DCA exhibits a high Km.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Specific Aim 4. Quantify the effects of DCA on human tyrosine metabolism and on its own biotransformation in relation to dose and genotype.

Study Type

Interventional

Enrollment (Actual)

2

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

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

22 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adults scheduled for elective surgery for benign liver disease.
  • Normal EKG and history
  • Normal baseline labs

Exclusion Criteria:

  • Pregnancy
  • severe anemia, defined as a hematocrit < 30%.
  • diabetes mellitus
  • renal insufficiency, defined as a serum creatinine > 1.5 mg/dl or a creatinine clearance < 60 ml/min
  • elevated liver enzymes
  • psychiatric illness requiring medication
  • primary biliary cirrhosis or any other form of cirrhosis
  • viral hepatitis or non-viral steatohepatitis
  • coronary heart disease, defined as requiring daily administration of anti-anginal drugs or as New York Heart Association Class III or IV heart failure
  • malignancy of any type in any anatomical location

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

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Haplotypes and DCA metabolism
Healthy men and women with different haplotypes will receive an infusion of leucine and tyrosine. The following day they begin a 5 day course of dichloroacetate (DCA)at a dose of 2.5mcg/kg/day. On day 6 they return and receive another infusion of leucine and tyrosine. After a 30 day washout period the subject returns and again receives an infusion of leucine and tyrosine. Then on day 2 they begin a dose of DCA at 25mg/kg for 5 days and then return for the final infusion of leucine and tyrosine.
Drug: Dichloroacetate
Healthy men and women with different haplotypes will receive an infusion of leucine and tyrosine. The following day they begin a 5 day course of dichloroacetate (DCA)at a dose of 2.5mcg/kg/day. On day 6 they return and receive another infusion of leucine and tyrosine. After a 30 day washout period the subject returns and again receives an infusion of leucine and tyrosine. Then on day 2 they begin a dose of DCA at 25mg/kg for 5 days and then return for the final infusion of leucine and tyrosine.
Other Names:
  • Leucine
  • DCA
  • Tyrosine
Genetic: Genotyping
Subjects will have 5 mls of blood drawn for genotyping
Other Names:
  • gene
  • haplotype
Other: Leucine
Healthy men and women with different haplotypes will receive an infusion of leucine and tyrosine. The following day they begin a 5 day course of dichloroacetate (DCA)at a dose of 2.5mcg/kg/day. On day 6 they return and receive another infusion of leucine and tyrosine. After a 30 day washout period the subject returns and again receives an infusion of leucine and tyrosine. Then on day 2 they begin a dose of DCA at 25mg/kg for 5 days and then return for the final infusion of leucine and tyrosine.
Other Names:
  • amino acid
Other: tyrosine
Healthy men and women with different haplotypes will receive an infusion of leucine and tyrosine. The following day they begin a 5 day course of dichloroacetate (DCA)at a dose of 2.5mcg/kg/day. On day 6 they return and receive another infusion of leucine and tyrosine. After a 30 day washout period the subject returns and again receives an infusion of leucine and tyrosine. Then on day 2 they begin a dose of DCA at 25mg/kg for 5 days and then return for the final infusion of leucine and tyrosine.
Other Names:
  • amino acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Interaction of DCA and/or Tyrosine Breakdown Products and Maleylacetoacetate Isomerase (MAAI) in Vivo.
Time Frame: One week

Subjects are administered an infusion of the amino acids leucine and tyrosine. The next day they start a five day course of dichloroacetate(DCA). At the end of five days they receive another infusion of tyrosine and leucine.

The pharmacokinetics of DCA is calculated following the second infusion.
One week

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Inhibition of Tyrosine and Individual's Haplotype
Time Frame: one week
Given the infusion of the above amino acids and DCA administration the inhibition of tyrosine will be measured in the KRT haplotype and non KRT haplotype.
one week

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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, 2011

Primary Completion (Actual)

January 1, 2012

Study Completion (Actual)

January 1, 2012

Study Registration Dates

First Submitted

March 17, 2009

First Submitted That Met QC Criteria

March 18, 2009

First Posted (Estimate)

March 19, 2009

Study Record Updates

Last Update Posted (Estimate)

June 3, 2015

Last Update Submitted That Met QC Criteria

June 2, 2015

Last Verified

July 1, 2013

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 14617-CP-001
  • 5R01ES014617 (U.S. NIH Grant/Contract)

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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