Trial Outcomes & Findings for Pharmacotoxicology of Trichloroethylene Metabolites (NCT NCT01128270)
NCT ID: NCT01128270
Last Updated: 2014-05-07
Results Overview
After 5 days of of therapeutic level Chloral Hydrate, the levels of Dichloroacetate in the plasma were measured.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
27 participants
Primary outcome timeframe
6 Days
Results posted on
2014-05-07
Participant Flow
Subjects were recruited using an ad approved by the Institutional Review Board (IRB) and by undergoing a screening exam to determine eligibility.
There were 27 total participants, with 4 eligible sessions (periods) for each, with the order to be randomized. As per CT.Gov instructions, the periods are identified by treatment rather than order.There were no planned comparisons between the arms of this pharmacological study. Withdrawals entered but did not reach baseline.
Participant milestones
| Measure |
All Subjects
The intent was to have all subjects participate in all four sessions (periods). These were environmental chloral hydrate +/- environmental DCA and therapeutic chloral hydrate +/- therapeutic DCA. Patient participation: 4 Sessions (N=2), 3 Sessions (N=1), 2 Sessions (N=6), 1 Session (N=8), 0 Sessions (N=10), Total: N=27 patients participated in 31 sessions.
|
|---|---|
|
Environment Chloral Hydrate and DCA (1A)
STARTED
|
7
|
|
Environment Chloral Hydrate and DCA (1A)
COMPLETED
|
7
|
|
Environment Chloral Hydrate and DCA (1A)
NOT COMPLETED
|
0
|
|
Environmental Chloral Hydrate (1B)
STARTED
|
8
|
|
Environmental Chloral Hydrate (1B)
COMPLETED
|
8
|
|
Environmental Chloral Hydrate (1B)
NOT COMPLETED
|
0
|
|
Therapeutic Chloral Hydrate and DCA (2A)
STARTED
|
8
|
|
Therapeutic Chloral Hydrate and DCA (2A)
COMPLETED
|
8
|
|
Therapeutic Chloral Hydrate and DCA (2A)
NOT COMPLETED
|
0
|
|
Therapeutic Chloral Hydrate (2B)
STARTED
|
8
|
|
Therapeutic Chloral Hydrate (2B)
COMPLETED
|
8
|
|
Therapeutic Chloral Hydrate (2B)
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacotoxicology of Trichloroethylene Metabolites
Baseline characteristics by cohort
| Measure |
All Subjects
n=27 Participants
Intent was to have all subjects participate in all sessions (periods)
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
27 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
28.0 years
STANDARD_DEVIATION 7.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
27 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 DaysAfter 5 days of of therapeutic level Chloral Hydrate, the levels of Dichloroacetate in the plasma were measured.
Outcome measures
| Measure |
Therapeutic Chloral Hydrate and DCA (2A)
n=8 Participants
Arm 2A: Subjects are given Chloral Hydrate (25 mg/kg for five nights) and therapeutic Dichloroacetate on Day 1 (25 mg/Kg.) Pharmacokinetics are done on days 1 and 5. This outcome only applies to Period 3.
|
Environmental Chloral Hydrate (1B)
Arm 1B: Subjects are given Chloral Hydrate (1.5mcg/kg for five nights). Pharmacokinetics are done on days 1 and 5.
|
Therapeutic Chloral Hydrate and DCA (2A)
Arm 2A: Subjects are given Chloral Hydrate (25 mg/kg for five nights) and therapeutic Dichloroacetate on Day 1 (25 mg/Kg.) Pharmacokinetics are done on days 1 and 5.
|
Therapeutic Chloral Hydrate (2B)
Arm 2B: Subjects are given Chloral Hydrate (25 mg/kg for five nights)(25 mg/Kg.) Pharmacokinetics are done on days 1 and 5.
|
|---|---|---|---|---|
|
Plasma DCA (Microgram/ml) After 5 Days of Therapeutic Level Chloral Hydrate on Arm 2A.
|
1.64 micrograms/ml
Standard Deviation 0.40
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 5 daysPopulation: This applies only to Arm 2B (Therapeutic Chloral Hydrate without DCA.
Elimination Half-life Difference on Arm 2B for 13C-Labeled trichloroacetate between day 5 (prolonged exposure) and day 1 (de novo exposure) after therapeutic level exposure to Chloral Hydrate. This outcome only applies to Period 4. Trichloroacetate is a marker, not an intervention.
Outcome measures
| Measure |
Therapeutic Chloral Hydrate and DCA (2A)
n=8 Participants
Arm 2A: Subjects are given Chloral Hydrate (25 mg/kg for five nights) and therapeutic Dichloroacetate on Day 1 (25 mg/Kg.) Pharmacokinetics are done on days 1 and 5. This outcome only applies to Period 3.
|
Environmental Chloral Hydrate (1B)
Arm 1B: Subjects are given Chloral Hydrate (1.5mcg/kg for five nights). Pharmacokinetics are done on days 1 and 5.
|
Therapeutic Chloral Hydrate and DCA (2A)
Arm 2A: Subjects are given Chloral Hydrate (25 mg/kg for five nights) and therapeutic Dichloroacetate on Day 1 (25 mg/Kg.) Pharmacokinetics are done on days 1 and 5.
|
Therapeutic Chloral Hydrate (2B)
Arm 2B: Subjects are given Chloral Hydrate (25 mg/kg for five nights)(25 mg/Kg.) Pharmacokinetics are done on days 1 and 5.
|
|---|---|---|---|---|
|
Difference in Half Lives 5 Day Less One Day Exposure in Trichloroacetate
|
2432 minutes
Standard Deviation 1403
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 5 daysPopulation: all eligible participants to arm 2B (Period 4)
The levels were clinically indetectable at baseline and the question was whether or not substantive levels would be noted at after 5 days exposure to Chloral Hydrate. Detectable, but low levels were detected.
Outcome measures
| Measure |
Therapeutic Chloral Hydrate and DCA (2A)
n=8 Participants
Arm 2A: Subjects are given Chloral Hydrate (25 mg/kg for five nights) and therapeutic Dichloroacetate on Day 1 (25 mg/Kg.) Pharmacokinetics are done on days 1 and 5. This outcome only applies to Period 3.
|
Environmental Chloral Hydrate (1B)
Arm 1B: Subjects are given Chloral Hydrate (1.5mcg/kg for five nights). Pharmacokinetics are done on days 1 and 5.
|
Therapeutic Chloral Hydrate and DCA (2A)
Arm 2A: Subjects are given Chloral Hydrate (25 mg/kg for five nights) and therapeutic Dichloroacetate on Day 1 (25 mg/Kg.) Pharmacokinetics are done on days 1 and 5.
|
Therapeutic Chloral Hydrate (2B)
Arm 2B: Subjects are given Chloral Hydrate (25 mg/kg for five nights)(25 mg/Kg.) Pharmacokinetics are done on days 1 and 5.
|
|---|---|---|---|---|
|
Urinary Maleylacetone Levels After 5 Day Exposure to Therapeutic Chloral Hydrate (Arm 2B)
|
0.38 micrograms per ml clorohydrate
Standard Deviation 0.17
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 dayPopulation: All eligible session completers
All four arms receive Chloral Hydrate on Day 1 (arms 1A and 1B environmental levels) and (arms 2A and 2B therapeutic levels). The question is could Dichloroacetate be detected in serum at the end of day 1. This analysis is purely descriptive, and no comparisons were planned.
Outcome measures
| Measure |
Therapeutic Chloral Hydrate and DCA (2A)
n=7 Participants
Arm 2A: Subjects are given Chloral Hydrate (25 mg/kg for five nights) and therapeutic Dichloroacetate on Day 1 (25 mg/Kg.) Pharmacokinetics are done on days 1 and 5. This outcome only applies to Period 3.
|
Environmental Chloral Hydrate (1B)
n=8 Participants
Arm 1B: Subjects are given Chloral Hydrate (1.5mcg/kg for five nights). Pharmacokinetics are done on days 1 and 5.
|
Therapeutic Chloral Hydrate and DCA (2A)
n=8 Participants
Arm 2A: Subjects are given Chloral Hydrate (25 mg/kg for five nights) and therapeutic Dichloroacetate on Day 1 (25 mg/Kg.) Pharmacokinetics are done on days 1 and 5.
|
Therapeutic Chloral Hydrate (2B)
n=8 Participants
Arm 2B: Subjects are given Chloral Hydrate (25 mg/kg for five nights)(25 mg/Kg.) Pharmacokinetics are done on days 1 and 5.
|
|---|---|---|---|---|
|
Detectable DCA After Day 1 in Serum (0=No 1=Yes)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
1A: Chloral Hydrate+DCA (Environmental)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Chloral Hydrate (Environmental)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Chloral Hydrate +DCA (Therapeutic Dose)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Chloral Hydrate (Therapeutic Dose)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
1A: Chloral Hydrate+DCA (Environmental)
n=7 participants at risk
This is Period 1. See description of periods for full details.
|
Chloral Hydrate (Environmental)
n=8 participants at risk
This is Period 2. See description of periods for full details.
|
Chloral Hydrate +DCA (Therapeutic Dose)
n=8 participants at risk
This is Period 3. See description of periods for full details.
|
Chloral Hydrate (Therapeutic Dose)
n=8 participants at risk
This is Period 4 See description of periods for full details.
|
|---|---|---|---|---|
|
Reproductive system and breast disorders
Abdominal cramps
|
0.00%
0/7 • Participants were followed for an average of 2 years.
|
12.5%
1/8 • Number of events 1 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/7 • Participants were followed for an average of 2 years.
|
12.5%
1/8 • Number of events 1 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
|
Respiratory, thoracic and mediastinal disorders
upper respiratory infection
|
0.00%
0/7 • Participants were followed for an average of 2 years.
|
12.5%
1/8 • Number of events 1 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/7 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
12.5%
1/8 • Number of events 1 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
|
Hepatobiliary disorders
Elevated liver enzymes
|
0.00%
0/7 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
12.5%
1/8 • Number of events 1 • Participants were followed for an average of 2 years.
|
|
Nervous system disorders
Headache
|
0.00%
0/7 • Participants were followed for an average of 2 years.
|
12.5%
1/8 • Number of events 1 • Participants were followed for an average of 2 years.
|
12.5%
1/8 • Number of events 1 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
|
Renal and urinary disorders
High Blood Pressure
|
0.00%
0/7 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
12.5%
1/8 • Number of events 1 • Participants were followed for an average of 2 years.
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.3%
1/7 • Number of events 1 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
|
Respiratory, thoracic and mediastinal disorders
Sore Throat
|
14.3%
1/7 • Number of events 1 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
0.00%
0/8 • Participants were followed for an average of 2 years.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place