Clinical trial NCT00865514: Pharmacotoxicology of Trichloroethylene Metabolites
Official title: Pharmacotoxicology of Trichloroethylene Metabolites: Short-term Effect of DCA on in Vivo Tyrosine Catabolism and MAAI Expression
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Healthy
Keywords: dichloroacetate
tyrosine
maleylacetoacetate
trichloroethylene
leucine
haplotype
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2009-03-19
Enrollment: 2
Sex: ALL
Minimum age (years): 22
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: The Interaction of DCA and/or Tyrosine Breakdown Products and Maleylacetoacetate Isomerase (MAAI) in Vivo.
timeFrame: One week
Secondary outcomes:
measure: Inhibition of Tyrosine and Individual's Haplotype
timeFrame: one week
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Peter W Stacpoole, PhD, MD
role: PRINCIPAL_INVESTIGATOR
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