NCT00865514

Brief Summary

This project focuses on the kinetics, metabolism and human toxicology of dichloroacetate (DCA)and tyrosine catabolism. The hypothesis is that tyrosine metabolism will be greatest in subject who harbor the KRT variant for GSTz1/MAAI for which DCA exhibits a high Km.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2

participants targeted

Target at below P25 for not_applicable healthy

Timeline
Completed

Started Aug 2011

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 17, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 19, 2009

Completed
2.4 years until next milestone

Study Start

First participant enrolled

August 1, 2011

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2012

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

June 20, 2013

Completed
Last Updated

June 3, 2015

Status Verified

July 1, 2013

Enrollment Period

5 months

First QC Date

March 17, 2009

Results QC Date

March 21, 2013

Last Update Submit

June 2, 2015

Conditions

Healthy

Keywords

dichloroacetatetyrosinemaleylacetoacetatetrichloroethyleneleucinehaplotype

Outcome Measures

Primary Outcomes (1)

  • The Interaction of DCA and/or Tyrosine Breakdown Products and Maleylacetoacetate Isomerase (MAAI) in Vivo.

    Subjects are administered an infusion of the amino acids leucine and tyrosine. The next day they start a five day course of dichloroacetate(DCA). At the end of five days they receive another infusion of tyrosine and leucine. The pharmacokinetics of DCA is calculated following the second infusion.

    One week

Secondary Outcomes (1)

  • Inhibition of Tyrosine and Individual's Haplotype

    one week

Study Arms (1)

Haplotypes and DCA metabolism

EXPERIMENTAL

Healthy men and women with different haplotypes will receive an infusion of leucine and tyrosine. The following day they begin a 5 day course of dichloroacetate (DCA)at a dose of 2.5mcg/kg/day. On day 6 they return and receive another infusion of leucine and tyrosine. After a 30 day washout period the subject returns and again receives an infusion of leucine and tyrosine. Then on day 2 they begin a dose of DCA at 25mg/kg for 5 days and then return for the final infusion of leucine and tyrosine.

Drug: DichloroacetateGenetic: GenotypingOther: LeucineOther: tyrosine

Interventions

DichloroacetateDRUG

Healthy men and women with different haplotypes will receive an infusion of leucine and tyrosine. The following day they begin a 5 day course of dichloroacetate (DCA)at a dose of 2.5mcg/kg/day. On day 6 they return and receive another infusion of leucine and tyrosine. After a 30 day washout period the subject returns and again receives an infusion of leucine and tyrosine. Then on day 2 they begin a dose of DCA at 25mg/kg for 5 days and then return for the final infusion of leucine and tyrosine.

Also known as: DCA, Leucine, Tyrosine
Haplotypes and DCA metabolism
GenotypingGENETIC

Subjects will have 5 mls of blood drawn for genotyping

Also known as: gene, haplotype
Haplotypes and DCA metabolism
LeucineOTHER

Healthy men and women with different haplotypes will receive an infusion of leucine and tyrosine. The following day they begin a 5 day course of dichloroacetate (DCA)at a dose of 2.5mcg/kg/day. On day 6 they return and receive another infusion of leucine and tyrosine. After a 30 day washout period the subject returns and again receives an infusion of leucine and tyrosine. Then on day 2 they begin a dose of DCA at 25mg/kg for 5 days and then return for the final infusion of leucine and tyrosine.

Also known as: amino acid
Haplotypes and DCA metabolism
tyrosineOTHER

Healthy men and women with different haplotypes will receive an infusion of leucine and tyrosine. The following day they begin a 5 day course of dichloroacetate (DCA)at a dose of 2.5mcg/kg/day. On day 6 they return and receive another infusion of leucine and tyrosine. After a 30 day washout period the subject returns and again receives an infusion of leucine and tyrosine. Then on day 2 they begin a dose of DCA at 25mg/kg for 5 days and then return for the final infusion of leucine and tyrosine.

Also known as: amino acid
Haplotypes and DCA metabolism

Eligibility Criteria

Age22 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Adults scheduled for elective surgery for benign liver disease.
  • Normal EKG and history
  • Normal baseline labs

You may not qualify if:

  • Pregnancy
  • severe anemia, defined as a hematocrit \< 30%.
  • diabetes mellitus
  • renal insufficiency, defined as a serum creatinine \> 1.5 mg/dl or a creatinine clearance \< 60 ml/min
  • elevated liver enzymes
  • psychiatric illness requiring medication
  • primary biliary cirrhosis or any other form of cirrhosis
  • viral hepatitis or non-viral steatohepatitis
  • coronary heart disease, defined as requiring daily administration of anti-anginal drugs or as New York Heart Association Class III or IV heart failure
  • malignancy of any type in any anatomical location

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Florida

Gainesville, Florida, 32610, United States

Location

Related Publications (128)

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MeSH Terms

Interventions

Dichloroacetic AcidLeucineTyrosineGenotypeGenesHaplotypesAmino Acids

Intervention Hierarchy (Ancestors)

ChloroacetatesAcetatesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsHydrocarbons, ChlorinatedHydrocarbons, HalogenatedHydrocarbonsAmino Acids, Branched-ChainAmino Acids, Peptides, and ProteinsAmino Acids, EssentialAmino Acids, AromaticAmino Acids, CyclicGenetic PhenomenaGenome ComponentsGenomeGenetic Structures

Results Point of Contact

Title
Dr. Peter W. Stacpoole
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
not applicable
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 17, 2009

First Posted

March 19, 2009

Study Start

August 1, 2011

Primary Completion

January 1, 2012

Study Completion

January 1, 2012

Last Updated

June 3, 2015

Results First Posted

June 20, 2013

Record last verified: 2013-07

Locations

US(1)