Pharmacotoxicology of Trichloroethylene Metabolites

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT00874276
First received: April 1, 2009
Last updated: May 9, 2013
Last verified: March 2013
Results First Received: March 11, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Parallel Assignment;   Masking: Open Label
Condition: Congenital Lactic Acidosis
Interventions: Drug: Dichloroacetate (DCA)
Genetic: Genetic Marker on Chromosome 14q24.3

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were recruited from a list of individuals who had already been genotyped. Subjects were called on the telephone to see if they wanted to participate in this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
21 subjects were consented to the study; however, 7 were excluded before being assigned to a group for the following reasons: works at night, on contraindicated medication, history of mitral valve prolapse, obesity, started smoking, and elevated liver enzymes.

Reporting Groups
  Description
Lack Any EGT Allele on GSTz1/MAAI Region of Chromosome 14q24.3

Both dichloroacetate 2.5ug and 25mg per kg per day and is administered for five days. (Biologic randomization)

Dichloroacetate 2.5ug/kg (Environmental) and 25mg/kg (clinical) are administered daily for 5 days in all subjects. Subjects are admitted to the clinical research center for 6 nights. The first day subjects are administer 2.5ug/kg/day. Frequent blood samples are collected over a 24 hour period. On days 2, 3, 4 the subjects receive a dose of DCA each day. On day 5 they receive a dose of DCA and pharmacokinetics are done for 24 hours then subjects are discharged.

1+ EGT Allele on GSTz1/MAAI Region of Chromosome 14q24.3

Both dichloroacetate 2.5ug and 25mg per kg per day and is administered for five days. (Biologic randomization)

Dichloroacetate 2.5ug/kg (Environmental) and 25mg/kg (clinical) are administered daily for 5 days in all subjects. Subjects are admitted to the clinical research center for 6 nights. The first day subjects are administer 2.5ug/kg/day. Frequent blood samples are collected over a 24 hour period. On days 2, 3, 4 the subjects receive a dose of DCA each day. On day 5 they receive a dose of DCA and pharmacokinetics are done for 24 hours then subjects are discharged.


Participant Flow:   Overall Study
    Lack Any EGT Allele on GSTz1/MAAI Region of Chromosome 14q24.3     1+ EGT Allele on GSTz1/MAAI Region of Chromosome 14q24.3  
STARTED     6     8  
COMPLETED     5     7  
NOT COMPLETED     1     1  
Withdrawal by Subject                 1                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Lack Any EGT Allele on GSTz1/MAAI Region of Chromosome 14q24.3 This study is a biological randomization for dichloroacetate pharmacodynamics for those with at least one EGT vs. without any EGT haplotype of the GSTZ1/MAAI gene which is located on chromosome 14q24.3.
1+ EGT Allele on GSTz1/MAAI Region of Chromosome 14q24.3 This study is a biological randomization for dichloroacetate pharmacodynamics for those with at least one EGT vs. without any EGT haplotype of the GSTZ1/MAAI gene which is located on chromosome 14q24.3.
Total Total of all reporting groups

Baseline Measures
    Lack Any EGT Allele on GSTz1/MAAI Region of Chromosome 14q24.3     1+ EGT Allele on GSTz1/MAAI Region of Chromosome 14q24.3     Total  
Number of Participants  
[units: participants]
  6     8     14  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     6     8     14  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  26.0  ± 4.6     28.2  ± 10.4     26.9  ± 7.3  
Gender  
[units: participants]
     
Female     3     5     8  
Male     3     3     6  
Region of Enrollment  
[units: participants]
     
United States     6     8     14  



  Outcome Measures
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1.  Primary:   Hypothesize That Subject's Genotype Will Determine How DCA is Metabolized.   [ Time Frame: 24 hours for analysis on Day 5, Clinical dose ]

2.  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.   [ Time Frame: 24 hours for analysis on Day 5, Environmental dose ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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 Stacpoole/Principal Investigator
Organization: University of Florida
phone: 1-352-273-9023
e-mail: pws@ufl.edu


No publications provided


Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT00874276     History of Changes
Obsolete Identifiers: NCT00874705
Other Study ID Numbers: 14617-CP-004
Study First Received: April 1, 2009
Results First Received: March 11, 2013
Last Updated: May 9, 2013
Health Authority: United States: Food and Drug Administration