Pharmacotoxicology of Trichloroethylene Metabolites

University of Florida

Status: Terminated

Conditions: Healthy

Treatments: Other: Leucine; Genetic: Genotyping; Other: tyrosine; Drug: Dichloroacetate

Study type: Interventional

Funder types: Other

Identifiers

NCT00865514

14617-CP-001

5R01ES014617 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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

Enrollment: 2 patients

Sex: All

Ages: 22 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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2 participants in 1 patient group

Haplotypes and DCA metabolism

Experimental group

Description:

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.

Treatment:

Drug: Dichloroacetate

Other: tyrosine

Genetic: Genotyping

Other: Leucine