Pharmacotoxicology of Trichloroethylene Metabolites

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01128270
First received: May 20, 2010
Last updated: April 8, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Healthy
Drug: Dichloroacetate environmental dose
Drug: Chloral Hydrate environmental dose
Drug: Dichloroacetate therapeutic dose
Drug: Chloral Hydrate therapeutic dose
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Pharmacotoxicology of Trichloroethylene Metabolites Aim 3

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Plasma DCA (Microgram/ml) After 5 Days of Therapeutic Level Chloral Hydrate on Arm 2A. [ Time Frame: 6 Days ] [ Designated as safety issue: No ]
    After 5 days of of therapeutic level Chloral Hydrate, the levels of Dichloroacetate in the plasma were measured.

  • Difference in Half Lives 5 Day Less One Day Exposure in Trichloroacetate [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    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.

  • Urinary Maleylacetone Levels After 5 Day Exposure to Therapeutic Chloral Hydrate (Arm 2B) [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Detectable DCA After Day 1 in Serum (0=No 1=Yes) [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    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.


Enrollment: 27
Study Start Date: April 2010
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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.

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

  Eligibility

Ages Eligible for Study:   21 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • healthy
  • normal screening labs

Exclusion Criteria:

  • no gastrointestinal surgery
  • no smoking
  • no medication
  • not pregnant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01128270

Locations
United States, Florida
University of Florida College of Medicine
Gainesville, Florida, United States, 32610
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Peter W. Stacpoole, PhD, MD University of Florida
  More Information

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01128270     History of Changes
Other Study ID Numbers: IRB#107-10, RO1ESO141617
Study First Received: May 20, 2010
Results First Received: November 20, 2013
Last Updated: April 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Florida:
Dichloroacetate
Chloral Hydrate
Metabolism

Additional relevant MeSH terms:
Chloral Hydrate
Trichloroethylene
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Inhalation
Anesthetics, General
Anesthetics

ClinicalTrials.gov processed this record on July 22, 2014