Pharmacotoxicology of Trichloroethylene Metabolites

NCT01128270 | Completed Phase 1 Results

• 2 other identifiers: IRB#107-10RO1ESO141617
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Keywords

Dichloroacetate; Chloral Hydrate; Metabolism

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Detectable DCA After Day 1 in Serum (0=No 1=Yes)

  1 day

Study Arms (4)

1A: Chloral Hydrate and DCA: Env

EXPERIMENTAL

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; Drug: Chloral Hydrate environmental dose

1B: Chloral Hydrate Env dose

EXPERIMENTAL

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

2A: Chloral Hydrate and DCA therapeutic

EXPERIMENTAL

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; Drug: Chloral Hydrate therapeutic dose

2B: Chloral Hydrate Therapeutic

EXPERIMENTAL

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

Interventions

Dichloroacetate environmental dose DRUG

On day 6 they receive Dichloroacetate 2.5 ug/kg orally times 1 and have pharmacokinetics.

Also known as: DCA

1A: Chloral Hydrate and DCA: Env

Chloral Hydrate environmental dose DRUG

Study subjects are given 1.5 ug/kg of Chloral Hydrate for 5 nights and pharmacokinetics are done on night 1 and 5.

1A: Chloral Hydrate and DCA: Env; 1B: Chloral Hydrate Env dose

Dichloroacetate therapeutic dose DRUG

Subjects receive 25 mg/kg DCA on Day 6. Pharmacokinetics are done on nights 1 and nights 5.

Also known as: DCA

2A: Chloral Hydrate and DCA therapeutic

Chloral Hydrate therapeutic dose DRUG

Subject is given 25 mg/kg of Chloral Hydrate for five nights.

2A: Chloral Hydrate and DCA therapeutic; 2B: Chloral Hydrate Therapeutic

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• healthy
• normal screening labs

You may not qualify if:

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

Sponsors & Collaborators

• University of Florida: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

Limitations and Caveats

Subjects were asked to wait 30 days in between doses of medication. Some of the participants could not wait the entire 4 months to finish the study and thus dropped out before they completed the 4 arms. Ten were enrolled, screened, but did not start

Results Point of Contact

• Title: Peter W. Stacpoole,MD
• Organization: University of Florida

pws@ufl.edu

(352) 273-9023

Study Officials

• Peter W. Stacpoole, PhD, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2010
• First Posted: May 21, 2010
• Study Start: April 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: May 7, 2014
• Results First Posted: May 7, 2014

Record last verified: 2014-04

Locations

US (1)