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Trial record 1 of 1 for:    12723459 [PUBMED-IDS]
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Pharmacotoxicology of Trichloroethylene Metabolites

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ClinicalTrials.gov Identifier: NCT00865514
Recruitment Status : Terminated (Difficulty in obtaining the solution from the compounding pharmacies caused a two year delay in start-up; the funding ended prior to study completion.)
First Posted : March 19, 2009
Results First Posted : June 20, 2013
Last Update Posted : June 3, 2015
Sponsor:
Information provided by (Responsible Party):
University of Florida

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Healthy
Interventions Drug: Dichloroacetate
Genetic: Genotyping
Other: Leucine
Other: tyrosine
Enrollment 2

Recruitment Details The participants were recruited by a posted advertisement.
Pre-assignment Details Two subjects were enrolled but did not participate in the study. One subject was delayed because the solution for the infusion had particles in it and then didn't continue(didn't receive any intervention) due to funding issues, and the second one was enrolled but didn't receive any intervention due to funding issues that have been explained.
Arm/Group Title Haplotypes and DCA Metabolism
Hide Arm/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.
Period Title: Overall Study
Started 2
Completed 0
Not Completed 2
Reason Not Completed
Infusion cost exceeded funding             2
Arm/Group Title Haplotypes and DCA Metabolism
Hide Arm/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.
Overall Number of Baseline Participants 2
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
<=18 years
0
   0.0%
Between 18 and 65 years
2
 100.0%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants
Female
1
  50.0%
Male
1
  50.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 2 participants
2
1.Primary Outcome
Title The Interaction of DCA and/or Tyrosine Breakdown Products and Maleylacetoacetate Isomerase (MAAI) in Vivo.
Hide Description

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.

Time Frame One week
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
No statistical analysis. The data was incomplete and was not analyzed.
Arm/Group Title The Interaction of DCA and/or Tyrosine Breakdown Products
Hide Arm/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.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Inhibition of Tyrosine and Individual's Haplotype
Hide Description 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.
Time Frame one week
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
No statistical analysis. The data was incomplete and was not analyzed.
Arm/Group Title Haplotypes and DCA Metabolism
Hide Arm/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.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame August 2011 to January 2012
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Haplotypes and DCA Metabolism
Hide Arm/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.
All-Cause Mortality
Haplotypes and DCA Metabolism
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Haplotypes and DCA Metabolism
Affected / at Risk (%) # Events
Total   0/2 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Haplotypes and DCA Metabolism
Affected / at Risk (%) # Events
Total   2/2 (100.00%)    
Nervous system disorders   
dizziness   1/2 (50.00%)  1
syncope  [1]  1/2 (50.00%)  1
Indicates events were collected by systematic assessment
[1]
Patient fainted for 15 seconds when blood was drawn
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Peter W. Stacpoole
Organization: University of Florida
Phone: (352) 273-9023
EMail: pws@ufl.edu
Publications:
LARC Monogr Eval Carcinog Risks Hum 11:263-276,1979.
Page N. Assessment of trichloroethylene as an occupational carcinogen. In: Davis W, Rosenfeld C, eds. Carcinogenic risks: strategies for intervention INSERM Symposia series Vol. 74. Lyon, France: International Agency for Reserach on Cancerl; IARC Scientific Publications E No. 25, 1979.
Federal Register 40(203):49032-49045, 1975.
Westrick JJ, Mello JW, Thomas RF. The groundwater supply survey. J Am Water Works 76:52, 1984.
Uden PCC, Miller JW. Chlorinated acids and chloral in drinking water. J Amer Water Works Assoc 75:524-527, 1983.
Jolley RL. Basic issues in water chlorination: a chemical perspective. In, Water chlorination: chemistry, environmental impact and health effects. Lewis Publ, Inc. Chelsea, MI 5:19-38, 1985.
Salmon AG, Jackson RJ, Smith MT. Chloral hydrate: cancer risk assessment of a drug previously presumed safe. The Toxicologist 11:350, 1991.
Liebreich O. Das Chloral hydrat, ein neues Hypnoticum und Anaestheticum, 3rd ed. Berlin: Otto Mullers Verlag, 1869.
Toxicological review of dichloroacetic acid (CAS No. 79-43-6). U.S. Environ. Protection Agency. Washington, DC, August, 2003.
Gonzalez-Leon A, Schultz IR, Bull RJ. Species differences in the toxicokinetics of dichloroacetate and trichloroacetate in F344 rats and B6C3F1 mice after prolonged administration in drinking water. Fundam Appl Toxicol Suppl 36, Abst. 168, p. 33, 1997.
NTP Technical Report. Toxicology and carcinogenesis study of chloral hydrate. NIH Publication No. 03-4437, 2002.
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Chloral hydrate. World Health Organization, 2004, pp. 317-358.
Kinter M, Sherman NE. Peptide Sequencng andIdentifcation Using Tandem Mass Specrometry. John Wiley and Sons, Inc., pp. 147-165, 2000.
Proteome Research: mass spectrometry. Peter James. Springer, pp. 5-9 2001.
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT00865514     History of Changes
Other Study ID Numbers: 14617-CP-001
5R01ES014617 ( U.S. NIH Grant/Contract )
First Submitted: March 17, 2009
First Posted: March 19, 2009
Results First Submitted: March 21, 2013
Results First Posted: June 20, 2013
Last Update Posted: June 3, 2015