Trial Outcomes & Findings for Pharmacotoxicology of Trichloroethylene Metabolites (NCT NCT00874276)
NCT ID: NCT00874276
Last Updated: 2015-06-04
Results Overview
Terminal half-life (the amount of time needed to clear one-half of dose of the drug).
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
21 participants
Primary outcome timeframe
24 hours for analysis on Day 5, Clinical dose
Results posted on
2015-06-04
Participant Flow
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.
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.
Participant milestones
| Measure |
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.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
8
|
|
Overall Study
COMPLETED
|
5
|
7
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
Pharmacotoxicology of Trichloroethylene Metabolites
Baseline characteristics by cohort
| Measure |
Lack Any EGT Allele on GSTz1/MAAI Region of Chromosome 14q24.3
n=6 Participants
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
n=8 Participants
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
n=14 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Continuous
|
26.0 years
STANDARD_DEVIATION 4.6 • n=99 Participants
|
28.2 years
STANDARD_DEVIATION 10.4 • n=107 Participants
|
26.9 years
STANDARD_DEVIATION 7.3 • n=206 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=99 Participants
|
8 participants
n=107 Participants
|
14 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 24 hours for analysis on Day 5, Clinical dosePopulation: All completing subjects (2 withdrawals have no pharmacokinetic data on this parameter) The intent was to accrue 12 per group but the grant ended before that could be achieved. Subjects were recruited from a large pool but the two genetically defined subgroups are rare.
Terminal half-life (the amount of time needed to clear one-half of dose of the drug).
Outcome measures
| Measure |
Lack Any EGT Allele on GSTz1/MAAI Region of Chromosome 14q24.3
n=5 Participants
Both dichloroacetate 2.5ug and 25mg per kg per day and is administered for five days. (Biologic randomization)
Dichloroacetate 2.5.ug/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, and 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
n=7 Participants
Both dichloroacetate 2.5ug and 25mg per kg per day and is administered for five days. (Biologic randomization)
Dichloroacetate 2.5.ug/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, and 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.
|
|---|---|---|
|
Hypothesize That Subject's Genotype Will Determine How DCA is Metabolized.
|
1592 Minutes
Interval 727.0 to 1774.0
|
232 Minutes
Interval 126.0 to 310.0
|
SECONDARY outcome
Timeframe: 24 hours for analysis on Day 5, Environmental dosePopulation: same as Primary
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.
Outcome measures
| Measure |
Lack Any EGT Allele on GSTz1/MAAI Region of Chromosome 14q24.3
n=5 Participants
Both dichloroacetate 2.5ug and 25mg per kg per day and is administered for five days. (Biologic randomization)
Dichloroacetate 2.5.ug/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, and 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
n=7 Participants
Both dichloroacetate 2.5ug and 25mg per kg per day and is administered for five days. (Biologic randomization)
Dichloroacetate 2.5.ug/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, and 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.
|
|---|---|---|
|
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.
|
65.4 minutes
Interval 56.3 to 66.4
|
74.3 minutes
Interval 58.9 to 90.4
|
Adverse Events
Lack Any EGT Allele on GSTz1/MAAI Region of Chromosome 14q24.3
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
1+ EGT Allele on GSTz1/MAAI Region of Chromosome 14q24.3
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lack Any EGT Allele on GSTz1/MAAI Region of Chromosome 14q24.3
n=6 participants at risk
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
n=8 participants at risk
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.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from 5/2008 to 2/2009
|
0.00%
0/8 • Adverse events were collected from 5/2008 to 2/2009
|
Other adverse events
| Measure |
Lack Any EGT Allele on GSTz1/MAAI Region of Chromosome 14q24.3
n=6 participants at risk
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
n=8 participants at risk
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.
|
|---|---|---|
|
General disorders
sleepiness
|
83.3%
5/6 • Number of events 7 • Adverse events were collected from 5/2008 to 2/2009
|
62.5%
5/8 • Number of events 5 • Adverse events were collected from 5/2008 to 2/2009
|
|
Gastrointestinal disorders
abdominal cramping and diarrhea
|
0.00%
0/6 • Adverse events were collected from 5/2008 to 2/2009
|
12.5%
1/8 • Number of events 1 • Adverse events were collected from 5/2008 to 2/2009
|
|
Immune system disorders
Hives
|
0.00%
0/6 • Adverse events were collected from 5/2008 to 2/2009
|
12.5%
1/8 • Number of events 1 • Adverse events were collected from 5/2008 to 2/2009
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/6 • Adverse events were collected from 5/2008 to 2/2009
|
12.5%
1/8 • Number of events 1 • Adverse events were collected from 5/2008 to 2/2009
|
|
Gastrointestinal disorders
Constipation
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from 5/2008 to 2/2009
|
0.00%
0/8 • Adverse events were collected from 5/2008 to 2/2009
|
|
Metabolism and nutrition disorders
slow clearance of DCA
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from 5/2008 to 2/2009
|
0.00%
0/8 • Adverse events were collected from 5/2008 to 2/2009
|
|
Musculoskeletal and connective tissue disorders
headache
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from 5/2008 to 2/2009
|
0.00%
0/8 • Adverse events were collected from 5/2008 to 2/2009
|
Additional Information
Dr. Peter Stacpoole/Principal Investigator
University of Florida
Phone: 1-352-273-9023
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place