Pharmacotoxicology of Trichloroethylene Metabolites

Pharmacotoxicology of Trichloroethylene Metabolites Aim 3

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Dichloroacetate environmental dose; Drug: Chloral Hydrate environmental dose; Drug: Dichloroacetate therapeutic dose; Drug: Chloral Hydrate therapeutic dose

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• healthy
• normal screening labs

Exclusion Criteria:

• no gastrointestinal surgery
• no smoking
• no medication
• not pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1A: Chloral Hydrate and DCA: Env; 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; On day 6 they receive Dichloroacetate 2.5 ug/kg orally times 1 and have pharmacokinetics.; Other Names: DCA; Drug: Chloral Hydrate environmental dose; Study subjects are given 1.5 ug/kg of Chloral Hydrate for 5 nights and pharmacokinetics are done on night 1 and 5.
EXPERIMENTAL: 1B: Chloral Hydrate Env dose; 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; Study subjects are given 1.5 ug/kg of Chloral Hydrate for 5 nights and pharmacokinetics are done on night 1 and 5.
EXPERIMENTAL: 2A: Chloral Hydrate and DCA therapeutic; 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; Subjects receive 25 mg/kg DCA on Day 6. Pharmacokinetics are done on nights 1 and nights 5.; Other Names: DCA; Drug: Chloral Hydrate therapeutic dose; Subject is given 25 mg/kg of Chloral Hydrate for five nights.
EXPERIMENTAL: 2B: Chloral Hydrate Therapeutic; 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; Subject is given 25 mg/kg of Chloral Hydrate for five nights.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (ACTUAL): October 1, 2012
• Study Completion (ACTUAL): October 1, 2012

Study Registration Dates

• First Submitted: May 20, 2010
• First Submitted That Met QC Criteria: May 20, 2010
• First Posted (ESTIMATE): May 21, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): May 7, 2014
• Last Update Submitted That Met QC Criteria: April 8, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Metabolism; Dichloroacetate; Chloral Hydrate
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Chloral Hydrate
• Other Study ID Numbers: IRB#107-10; RO1ESO141617 (OTHER_GRANT: National Institute of Health RO1ESO14167)