Pharmacotoxicology of Trichloroethylene Metabolites

Study Overview
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Brief Summary
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This is a research study to look at how Dichloroacetate (DCA), and investigational drug and chloral hydrate are broken down in the body. The purpose of the study is to better understand how humans metabolize these two common chemicals that are widely present in the environment. The study focuses on how the drug chloral hydrate is broken down and how it effects DCA

Detailed Description
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The subject's general health is assessed by a history and physical exam and routine blood work. I normal the individual undergoes five nights of receiving 1.5ug/kg of chloral hydrate. On day 6 the individual receives 2.5 micrograms/kg of Dichloroacetate (DCA) and kinetics are drawn. After 30 days the subject comes back and receives 1.5ug/kg of chloral hydrate for five nights and has kinetics drawn on night one and five. On days 6-9 the subject returns for a blood draw. After 30 days the same process as above is done except the subject receives 1gram of chloral hydrate for five nights and 25mg/kg of Dichloroacetate one day then 30 days later the subject receives 1gram of chloral hydrate for five nights and has kinetics done on night one and five and blood samples drawn on days 6-9

Official Title
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Pharmacotoxicology of Trichloroethylene Metabolites Aim 3

Conditions
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Healthy

Intervention / Treatment
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* Drug: Dichloroacetate environmental dose
* Drug: Chloral Hydrate environmental dose
* Drug: Dichloroacetate therapeutic dose
* Drug: Chloral Hydrate therapeutic dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy normal screening labs Exclusion Criteria: no gastrointestinal surgery no smoking no medication not pregnant

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1A: Chloral Hydrate and DCA: Env<br>Subjects consume Chloral Hydrate 1.5ug/kg by mouth for 5 nights. On the 6th day they consume DCA 2.5ug/kg by mouth and have blood samples drawn. (Period 1) | Drug: Dichloroacetate environmental dose<br>* On day 6 they receive Dichloroacetate 2.5 ug/kg orally times 1 and have pharmacokinetics.<br>* Other names: DCA;Drug: Chloral Hydrate environmental dose<br>* Study subjects are given 1.5 ug/kg of Chloral Hydrate for 5 nights and pharmacokinetics are done on night 1 and 5.<br>|
| Experimental: 1B: Chloral Hydrate Env dose<br>Drug Study Subjects are admitted to the clinical research unit and receive 1.5 ug/kg (environmental dose) of Chloral Hydrate for 5 nights. Pharmacokinetics are done on days 1 and day 5. (Period 2) | Drug: Chloral Hydrate environmental dose<br>* Study subjects are given 1.5 ug/kg of Chloral Hydrate for 5 nights and pharmacokinetics are done on night 1 and 5.<br>|
| Experimental: 2A: Chloral Hydrate and DCA therapeutic<br>Drug Study Subjects are admitted to the clinical research center and receive a clinical dose of Chloral Hydrate for 5 nights (25mg/kg). On day 6 they are given a clinical dose (25mg/kg)of Dichloroacetate. (Period 3) | Drug: Dichloroacetate therapeutic dose<br>* Subjects receive 25 mg/kg DCA on Day 6. Pharmacokinetics are done on nights 1 and nights 5.<br>* Other names: DCA;Drug: Chloral Hydrate therapeutic dose<br>* Subject is given 25 mg/kg of Chloral Hydrate for five nights.<br>|
| Experimental: 2B: Chloral Hydrate Therapeutic<br>Subjects are given 25 mg/kg of Chloral Hydrate for five nights. Pharmacokinetics are done on days 1 and 5. (Period 4) | Drug: Chloral Hydrate therapeutic dose<br>* Subject is given 25 mg/kg of Chloral Hydrate for five nights.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma DCA (Microgram/ml) After 5 Days of Therapeutic Level Chloral Hydrate on Arm 2A. | After 5 days of of therapeutic level Chloral Hydrate, the levels of Dichloroacetate in the plasma were measured. | 6 Days | 
| Difference in Half Lives 5 Day Less One Day Exposure in Trichloroacetate | 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. | 5 days | 
| Urinary Maleylacetone Levels After 5 Day Exposure to Therapeutic Chloral Hydrate (Arm 2B) | 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. | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detectable DCA After Day 1 in Serum (0=No 1=Yes) | 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. | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dichloroacetate, Chloral Hydrate, Metabolism