HealthyNCT00865514

Pharmacotoxicology of Trichloroethylene Metabolites

A study testing Dichloroacetate, Genotyping and Leucine in people with Healthy, run by University of Florida at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 22 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Dichloroacetate, Genotyping and Leucine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 2 participants
Where: 1 siteUnited States
Study dates: Aug 2011to Jan 2012
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 22 to 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

Show all 10Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Florida
Gainesville, Florida, 32610

Other trials in United States

About this study

Official title: Pharmacotoxicology of Trichloroethylene Metabolites: Short-term Effect of DCA on in Vivo Tyrosine Catabolism and MAAI Expression

Read the detailed description

Specific Aim 4. Quantify the effects of DCA on human tyrosine metabolism and on its own biotransformation in relation to dose and genotype.

Conditions: Healthy
Being tested: Dichloroacetate, Genotyping, Leucine, tyrosine
Keywords: dichloroacetate, tyrosine, maleylacetoacetate, trichloroethylene, leucine, haplotype

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DichloroacetateDrug
Also called DCA, Leucine, Tyrosine
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.
GenotypingGenetic
Also called gene, haplotype
Subjects will have 5 mls of blood drawn for genotyping
LeucineOther
Also called amino acid
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.
tyrosineOther
Also called amino acid
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.

Study groups in NCT00865514
Study group	Role	What they receive
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. Receives: Drug: Dichloroacetate; Genetic: Genotyping; Other: Leucine; Other: tyrosine

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: One week

Secondary outcomes (1)

Inhibition of Tyrosine and Individual's Haplotype
Given the infusion of the above amino acids and DCA administration the inhibition of tyrosine will be measured in the KRT haplotype and non KRT haplotype.
Measured: one week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2011Jan 2012

First posted19 Mar 2009 (estimated)
Study startAug 2011
Primary completionJan 2012
Study completionJan 2012

Why it stopped: Difficulty in obtaining the solution from the compounding pharmacies caused a two year delay in start-up; the funding ended prior to study completion.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (128)Papers the sponsor has linked to this study.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by University of FloridaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 2 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00865514
Sponsor's protocol ID: 14617-CP-001
Other IDs: 5R01ES014617
Status last verified: Jul 2013
First submitted: 17 Mar 2009
Last updated: 3 Jun 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

National Toxicology Program. Toxicology Carcinogenesis Studies of Trichloroethylene (Without Epichlorohydon)(CAS No. 7.9-011-6) in F3dd/N Rats B6C3F1 Mice (Gavage Studies). Research Triangle Park, NC: US Department of Health Human Services; Technical report series No. 243; NIH Publication 9:0-1779, 1990.
LARC Monogr Eval Carcinog Risks Hum 11:263-276,1979.
Page NN. Assessment of trichloroethylene as an occupational carcinogen. IARC Sci Publ (1971). 1979;(25):75-9.
PubMed 457166
Federal Register 40(203):49032-49045, 1975.
Westrick JJ, Mello JW, Thomas RF. The groundwater supply survey. J Am Water Works 76:52, 1984.
Josephson J. ES Views: Implementing Superfund. Environ Sci Technol. 1986 Jan 1;20(1):23-8. doi: 10.1021/es00143a601. No abstract available.
PubMed 22300147
Brown LP, Farrar DG, de Rooij CG. Health risk assessment of environmental exposure to trichloroethylene. Regul Toxicol Pharmacol. 1990 Feb;11(1):24-41. doi: 10.1016/0273-2300(90)90005-v.
PubMed 2184464
Steinberg AD, DeSesso JM. Have animal data been used inappropriately to estimate risks to humans from environmental trichloroethylene? Regul Toxicol Pharmacol. 1993 Oct;18(2):137-53. doi: 10.1006/rtph.1993.1049.
PubMed 8278637
Nelson MA, Bull RJ. Induction of strand breaks in DNA by trichloroethylene and metabolites in rat and mouse liver in vivo. Toxicol Appl Pharmacol. 1988 Jun 15;94(1):45-54. doi: 10.1016/0041-008x(88)90335-3.
PubMed 3376113
Larson JL, Bull RJ. Species differences in the metabolism of trichloroethylene to the carcinogenic metabolites trichloroacetate and dichloroacetate. Toxicol Appl Pharmacol. 1992 Aug;115(2):278-85. doi: 10.1016/0041-008x(92)90333-n.
PubMed 1641861
Henschler D. Metabolism and mutagenicity of halogenated olefins--a comparison of structure and activity. Environ Health Perspect. 1977 Dec;21:61-4. doi: 10.1289/ehp.772161.
PubMed 348459
Buben JA, O'Flaherty EJ. Delineation of the role of metabolism in the hepatotoxicity of trichloroethylene and perchloroethylene: a dose-effect study. Toxicol Appl Pharmacol. 1985 Mar 30;78(1):105-22. doi: 10.1016/0041-008x(85)90310-2.
PubMed 2994252
Bruckner JV, Davis BD, Blancato JN. Metabolism, toxicity, and carcinogenicity of trichloroethylene. Crit Rev Toxicol. 1989;20(1):31-50. doi: 10.3109/10408448909037475.
PubMed 2673291
Van Duuren BL, Banerjee S. Covalent interaction of metabolites of the carcinogen trichloroethylene in rat hepatic microsomes. Cancer Res. 1976 Jul;36(7 PT 1):2419-22.
PubMed 1277148
Henschler D, Romen W, Elsasser HM, Reichert D, Eder E, Radwan Z. Carcinogenicity study of trichloroethylene by longterm inhalation in three animal species. Arch Toxicol. 1980 Feb;43(4):237-48. doi: 10.1007/BF00366179.
PubMed 7387385

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis

All Healthy trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacotoxicology of Trichloroethylene Metabolites: Short-term Effect of DCA on in Vivo Tyrosine Catabolism and MAAI Expression
ClinicalTrials.gov ID: NCT00865514
Acronym / sponsor ID: 14617-CP-001
Conditions: Healthy
Keywords: dichloroacetate, tyrosine, maleylacetoacetate, trichloroethylene, leucine, haplotype
Study type: Interventional
Recruitment status: TerminatedReason stopped: Difficulty in obtaining the solution from the compounding pharmacies caused a two year delay in start-up; the funding ended prior to study completion.
Enrolment: 2 participants (actual)
Lead sponsor: University of FloridaUniversity, hospital or other
Study start: Aug 2011
Primary completion: Jan 2012 (actual)
Study completion: Jan 2012 (actual)
First posted: 19 Mar 2009 (estimated)
Results: Posted 20 Jun 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Specific Aim 4. Quantify the effects of DCA on human tyrosine metabolism and on its own biotransformation in relation to dose and genotype.

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Haplotypes and DCA metabolism	Experimental	Drug: Dichloroacetate, Genetic: Genotyping, Other: Leucine, Other: tyrosineHealthy 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.

Who may qualify

Ages: 22 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (10 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DichloroacetateAlso: DCA, Leucine, TyrosineHealthy 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	Haplotypes and DCA metabolism
GenotypingAlso: gene, haplotypeSubjects will have 5 mls of blood drawn for genotyping	Genetic	Haplotypes and DCA metabolism
LeucineAlso: amino acidHealthy 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.	Other	Haplotypes and DCA metabolism
tyrosineAlso: amino acidHealthy 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.	Other	Haplotypes and DCA metabolism

Primary outcome

The Interaction of DCA and/or Tyrosine Breakdown Products and Maleylacetoacetate Isomerase (MAAI) in Vivo.
Time frame: One week
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.

1 secondary outcome

Inhibition of Tyrosine and Individual's Haplotype
Time frame: one week

Results and safety

Results posted to the registry on 20 Jun 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Haplotypes and DCA Metabolism	2	0

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

Time frame: One week

Population analysed: No statistical analysis. The data was incomplete and was not analyzed.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: August 2011 to January 2012. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Haplotypes and DCA Metabolism	0 of 2 (0%)	2 of 2 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
BackgroundNational Toxicology Program. Toxicology Carcinogenesis Studies of Trichloroethylene (Without Epichlorohydon)(CAS No. 7.9-011-6) in F3dd/N Rats B6C3F1 Mice (Gavage Studies). Research Triangle Park, NC: US Department of Health Human Services; Technical report series No. 243; NIH Publication 9:0-1779, 1990.
BackgroundLARC Monogr Eval Carcinog Risks Hum 11:263-276,1979.
Background: PubMed 457166Page NN. Assessment of trichloroethylene as an occupational carcinogen. IARC Sci Publ (1971). 1979;(25):75-9.
BackgroundFederal Register 40(203):49032-49045, 1975.
BackgroundWestrick JJ, Mello JW, Thomas RF. The groundwater supply survey. J Am Water Works 76:52, 1984.
Background: PubMed 22300147Josephson J. ES Views: Implementing Superfund. Environ Sci Technol. 1986 Jan 1;20(1):23-8. doi: 10.1021/es00143a601. No abstract available.
Background: PubMed 2184464Brown LP, Farrar DG, de Rooij CG. Health risk assessment of environmental exposure to trichloroethylene. Regul Toxicol Pharmacol. 1990 Feb;11(1):24-41. doi: 10.1016/0273-2300(90)90005-v.
Background: PubMed 8278637Steinberg AD, DeSesso JM. Have animal data been used inappropriately to estimate risks to humans from environmental trichloroethylene? Regul Toxicol Pharmacol. 1993 Oct;18(2):137-53. doi: 10.1006/rtph.1993.1049.
Background: PubMed 3376113Nelson MA, Bull RJ. Induction of strand breaks in DNA by trichloroethylene and metabolites in rat and mouse liver in vivo. Toxicol Appl Pharmacol. 1988 Jun 15;94(1):45-54. doi: 10.1016/0041-008x(88)90335-3.
Background: PubMed 1641861Larson JL, Bull RJ. Species differences in the metabolism of trichloroethylene to the carcinogenic metabolites trichloroacetate and dichloroacetate. Toxicol Appl Pharmacol. 1992 Aug;115(2):278-85. doi: 10.1016/0041-008x(92)90333-n.
Background: PubMed 348459Henschler D. Metabolism and mutagenicity of halogenated olefins--a comparison of structure and activity. Environ Health Perspect. 1977 Dec;21:61-4. doi: 10.1289/ehp.772161.
Background: PubMed 2994252Buben JA, O'Flaherty EJ. Delineation of the role of metabolism in the hepatotoxicity of trichloroethylene and perchloroethylene: a dose-effect study. Toxicol Appl Pharmacol. 1985 Mar 30;78(1):105-22. doi: 10.1016/0041-008x(85)90310-2.

Related trials for Healthy

Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Peter W Stacpoole, PhD, MD principal investigator

University of Florida

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Dichloroacetate, Genotyping and Leucine in people with Healthy, run by University of Florida at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Interaction of DCA and/or Tyrosine Breakdown Products and Maleylacetoacetate Isomerase (MAAI) in Vivo. (time frame: One week). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00865514, which also lists 128 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2015.