Pharmacotoxicology of Trichloroethylene Metabolites

Congenital Lactic Acidosis Clinical Trial

Official title:

Pharmacotoxicology of Trichloroethylene Metabolites

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00874276
• Other study ID #: 14617-CP-004
• Status: Completed
• Phase: N/A
• First received: April 1, 2009
• Last updated: June 3, 2015
• Start date: August 2009
• Est. completion date: November 2012

Study information

• Verified date: March 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

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.

Description:

The arms of the study involves determining the haplotype of individuals enrolled. Then participants were divided into two groups based on their genotype. The groups include a genotype with an EGT alle and a group of genotype without an EGT alle. All subjects first took a low dose of DCA 2.5ug/kg for 5 days then wait 30 days and take a therapeutic dose of DCA 25mg/kg for 5 days On the first day and on the 5th day of taking DCA kinetics were be done. A total of 16 blood samples were obtained through an intravenous catheter. Urine collection will also occur.

Population pharmacogenetic analysis of MAI allelic frequencies and the GC or LC-MS/MS techniques for blood or urinary metabolites were used in this investigation. Pharmacokinetic data was used to determine metabolism rate of DCA for each allele

Other known NCT identifiers

• NCT00874705

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 50 Years

Eligibility

Inclusion Criteria:

• Healthy volunteers

Exclusion Criteria:

• Pregnancy

• Other medications

• Psychiatric illness on meds

• Abnormal labs

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Acidosis, Lactic
• Congenital Lactic Acidosis

Intervention

Drug:
• Dichloroacetate (DCA)
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.

Genetic:
• Genetic Marker on Chromosome 14q24.3
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.

Locations

Country	Name	City	State
United States	University of Florida Shands Hospital	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	Terminal half-life (the amount of time needed to clear one-half of the dose of drug)for the environmental dose 2.5 ug/kg/day.	24 hours for analysis on Day 5, Environmental dose	No