Pharmacotoxicology of Trichloroethylene Metabolites

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00865514
• Other study ID #: 14617-CP-001
• Secondary ID: 5R01ES014617
• Status: Terminated
• Phase: N/A
• First received: March 17, 2009
• Last updated: June 2, 2015
• Start date: August 2011
• Est. completion date: January 2012

Study information

• Verified date: July 2013
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 22 Years to 60 Years

Eligibility

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 Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy

Intervention

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.

Genetic:
• Genotyping
Subjects will have 5 mls of blood drawn for genotyping

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.
• 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.

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

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* Note: There are 128 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Interaction of DCA and/or Tyrosine Breakdown Products and Maleylacetoacetate Isomerase (MAAI) in Vivo.	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	No
Secondary	Inhibition of Tyrosine and Individual's Haplotype	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	No