Pharmacotoxicology of Trichloroethylene Metabolites

NCT00874276 | Completed Results DMC

• 1 other identifier: 14617-CP-004
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Congenital Lactic Acidosis

Keywords

DCA; Dichloroacetate; Trichloroacetate

Outcome Measures

Primary Outcomes (1)

• Hypothesize That Subject's Genotype Will Determine How DCA is Metabolized.

  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 Outcomes (1)

• 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.

  24 hours for analysis on Day 5, Environmental dose

Study Arms (2)

No EGT Allele, slow metabolizers for DCA

EXPERIMENTAL

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); Genetic: Genetic Marker on Chromosome 14q24.3

1+ EGT Allele, fast metabolizers for DCA

EXPERIMENTAL

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); Genetic: Genetic Marker on Chromosome 14q24.3

Interventions

Dichloroacetate (DCA) DRUG

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.

Also known as: genotype

1+ EGT Allele, fast metabolizers for DCA; No EGT Allele, slow metabolizers for DCA

Genetic Marker on Chromosome 14q24.3 GENETIC

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.

Also known as: Genetic Marker, Haplotypes

1+ EGT Allele, fast metabolizers for DCA; No EGT Allele, slow metabolizers for DCA

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers

You may not qualify if:

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

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida Shands Hospital

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Interventions

Dichloroacetic Acid; Genotype; Genetic Markers; Haplotypes

Intervention Hierarchy (Ancestors)

Chloroacetates; Acetates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydrocarbons, Chlorinated; Hydrocarbons, Halogenated; Hydrocarbons; Genetic Phenomena; Biomarkers; Biological Factors; Phenotype

Results Point of Contact

• Title: Dr. Peter Stacpoole/Principal Investigator
• Organization: University of Florida

pws@ufl.edu

1-352-273-9023

Study Officials

• Peter W Stacpoole, PhD, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2009
• First Posted: April 2, 2009
• Study Start: August 1, 2009
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: June 4, 2015
• Results First Posted: June 20, 2013

Record last verified: 2013-03

Locations

US (1)