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| ID | Type | Description | Link |
|---|---|---|---|
| 5R01ES014617 | U.S. NIH Grant/Contract | View source |
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Difficulty in obtaining the solution from the compounding pharmacies caused a two year delay in start-up; the funding ended prior to study completion.
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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.
Specific Aim 4. Quantify the effects of DCA on human tyrosine metabolism and on its own biotransformation in relation to dose and genotype.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dichloroacetate | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | one week |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Peter W Stacpoole, PhD, MD | University of Florida | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Florida | Gainesville | Florida | 32610 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | 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. | ||
| Background | LARC Monogr Eval Carcinog Risks Hum 11:263-276,1979. | ||
| 457166 | Background | Page NN. Assessment of trichloroethylene as an occupational carcinogen. IARC Sci Publ (1971). 1979;(25):75-9. | |
| Background | Federal Register 40(203):49032-49045, 1975. | ||
| Background | Westrick JJ, Mello JW, Thomas RF. The groundwater supply survey. J Am Water Works 76:52, 1984. |
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Two subjects were enrolled but did not participate in the study. One subject was delayed because the solution for the infusion had particles in it and then didn't continue(didn't receive any intervention) due to funding issues, and the second one was enrolled but didn't receive any intervention due to funding issues that have been explained.
The participants were recruited by a posted advertisement.
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| ID | Title | Description |
|---|---|---|
| FG000 | Haplotypes and DCA Metabolism | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Haplotypes and DCA Metabolism | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | No statistical analysis. The data was incomplete and was not analyzed. | Posted | One week |
|
August 2011 to January 2012
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Haplotypes and DCA Metabolism | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| dizziness | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Peter W. Stacpoole | University of Florida | (352) 273-9023 | pws@ufl.edu |
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| ID | Term |
|---|---|
| D003999 | Dichloroacetic Acid |
| D007930 | Leucine |
| D014443 | Tyrosine |
| D005838 | Genotype |
| D005796 | Genes |
| D006239 | Haplotypes |
| D000596 | Amino Acids |
| ID | Term |
|---|---|
| D062845 | Chloroacetates |
| D000085 | Acetates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
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|
|
| Genotyping | Genetic | Subjects will have 5 mls of blood drawn for genotyping |
|
|
| Leucine | Other | 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. |
|
|
| tyrosine | Other | 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. |
|
|
| 22300147 | Background | Josephson J. ES Views: Implementing Superfund. Environ Sci Technol. 1986 Jan 1;20(1):23-8. doi: 10.1021/es00143a601. No abstract available. |
| 2184464 | Background | 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. |
| 8278637 | Background | 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. |
| 3376113 | Background | 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. |
| 1641861 | Background | 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. |
| 348459 | Background | 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. |
| 2994252 | Background | 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. |
| 2673291 | Background | Bruckner JV, Davis BD, Blancato JN. Metabolism, toxicity, and carcinogenicity of trichloroethylene. Crit Rev Toxicol. 1989;20(1):31-50. doi: 10.3109/10408448909037475. |
| 1277148 | Background | 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. |
| 7387385 | Background | 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. |
| 3868383 | Background | Elcombe CR. Species differences in carcinogenicity and peroxisome proliferation due to trichloroethylene: a biochemical human hazard assessment. Arch Toxicol Suppl. 1985;8:6-17. doi: 10.1007/978-3-642-69928-3_2. |
| 12183104 | Background | Forkert PG, Lash LH, Nadeau V, Tardif R, Simmonds A. Metabolism and toxicity of trichloroethylene in epididymis and testis. Toxicol Appl Pharmacol. 2002 Aug 1;182(3):244-54. doi: 10.1006/taap.2002.9421. |
| 15375293 | Background | Xu H, Tanphaichitr N, Forkert PG, Anupriwan A, Weerachatyanukul W, Vincent R, Leader A, Wade MG. Exposure to trichloroethylene and its metabolites causes impairment of sperm fertilizing ability in mice. Toxicol Sci. 2004 Dec;82(2):590-7. doi: 10.1093/toxsci/kfh277. Epub 2004 Sep 16. |
| 14975357 | Background | Gilbert KM, Whitlow AB, Pumford NR. Environmental contaminant and disinfection by-product trichloroacetaldehyde stimulates T cells in vitro. Int Immunopharmacol. 2004 Jan;4(1):25-36. doi: 10.1016/j.intimp.2003.10.001. |
| 14615234 | Background | Reif JS, Burch JB, Nuckols JR, Metzger L, Ellington D, Anger WK. Neurobehavioral effects of exposure to trichloroethylene through a municipal water supply. Environ Res. 2003 Nov;93(3):248-58. doi: 10.1016/s0013-9351(03)00131-2. |
| 10457397 | Background | Guehl D, Bezard E, Dovero S, Boraud T, Bioulac B, Gross C. Trichloroethylene and parkinsonism: a human and experimental observation. Eur J Neurol. 1999 Sep;6(5):609-11. doi: 10.1046/j.1468-1331.1999.650609.x. |
| 22263679 | Background | Miller JW, Uden PC. Characterization of nonvolatile aqueous chlorination products of humic substances. Environ Sci Technol. 1983 Mar 1;17(3):150-7. doi: 10.1021/es00109a006. No abstract available. |
| Background | Uden PCC, Miller JW. Chlorinated acids and chloral in drinking water. J Amer Water Works Assoc 75:524-527, 1983. |
| 1464809 | Background | Mughal FH. Chlorination of drinking water and cancer: a review. J Environ Pathol Toxicol Oncol. 1992 Sep-Oct;11(5-6):287-92. No abstract available. |
| Background | Jolley RL. Basic issues in water chlorination: a chemical perspective. In, Water chlorination: chemistry, environmental impact and health effects. Lewis Publ, Inc. Chelsea, MI 5:19-38, 1985. |
| 2554095 | Background | Stacpoole PW. The pharmacology of dichloroacetate. Metabolism. 1989 Nov;38(11):1124-44. doi: 10.1016/0026-0495(89)90051-6. |
| 8971140 | Background | Abbas RR, Seckel CS, Kidney JK, Fisher JW. Pharmacokinetic analysis of chloral hydrate and its metabolism in B6C3F1 mice. Drug Metab Dispos. 1996 Dec;24(12):1340-6. |
| 15070938 | Background | Duncan GE, Perkins LA, Theriaque DW, Neiberger RE, Stacpoole PW. Dichloroacetate therapy attenuates the blood lactate response to submaximal exercise in patients with defects in mitochondrial energy metabolism. J Clin Endocrinol Metab. 2004 Apr;89(4):1733-8. doi: 10.1210/jc.2003-031684. |
| 16651305 | Background | Stacpoole PW, Kerr DS, Barnes C, Bunch ST, Carney PR, Fennell EM, Felitsyn NM, Gilmore RL, Greer M, Henderson GN, Hutson AD, Neiberger RE, O'Brien RG, Perkins LA, Quisling RG, Shroads AL, Shuster JJ, Silverstein JH, Theriaque DW, Valenstein E. Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children. Pediatrics. 2006 May;117(5):1519-31. doi: 10.1542/peds.2005-1226. |
| 16476929 | Background | Kaufmann P, Engelstad K, Wei Y, Jhung S, Sano MC, Shungu DC, Millar WS, Hong X, Gooch CL, Mao X, Pascual JM, Hirano M, Stacpoole PW, DiMauro S, De Vivo DC. Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial. Neurology. 2006 Feb 14;66(3):324-30. doi: 10.1212/01.wnl.0000196641.05913.27. |
| Background | Salmon AG, Jackson RJ, Smith MT. Chloral hydrate: cancer risk assessment of a drug previously presumed safe. The Toxicologist 11:350, 1991. |
| Background | Liebreich O. Das Chloral hydrat, ein neues Hypnoticum und Anaestheticum, 3rd ed. Berlin: Otto Mullers Verlag, 1869. |
| 2714158 | Background | Reimche LD, Sankaran K, Hindmarsh KW, Kasian GF, Gorecki DK, Tan L. Chloral hydrate sedation in neonates and infants--clinical and pharmacologic considerations. Dev Pharmacol Ther. 1989;12(2):57-64. |
| 2738727 | Background | Hartley S, Franck LS, Lundergan F. Maintenance sedation of agitated infants in the neonatal intensive care unit with chloral hydrate: new concerns. J Perinatol. 1989 Jun;9(2):162-4. No abstract available. |
| 12504208 | Background | Krsek P, Sebronova V, Prochazka T, Maulisova A, Komarek V. Successful treatment of Ohtahara syndrome with chloral hydrate. Pediatr Neurol. 2002 Nov;27(5):388-91. doi: 10.1016/s0887-8994(02)00464-2. |
| 2026812 | Background | Greenberg SB, Faerber EN, Aspinall CL. High dose chloral hydrate sedation for children undergoing CT. J Comput Assist Tomogr. 1991 May-Jun;15(3):467-9. doi: 10.1097/00004728-199105000-00023. |
| 3470333 | Background | Nathan JE. Management of the refractory young child with chloral hydrate: dosage selection. ASDC J Dent Child. 1987 Mar-Apr;54(2):93-100. |
| 3714334 | Background | Kuhn JP. CT of the body in children. Pediatr Ann. 1986 May;15(5):367, 371-3, 376-82. doi: 10.3928/0090-4481-19860501-07. |
| 3085006 | Background | Weir MR, Segapeli JH, Tremper LJ. Sedation for pediatric procedures. Mil Med. 1986 Mar;151(3):181-4. No abstract available. |
| 512063 | Background | Miller RR, Greenblatt DJ. Clinical effects of chloral hydrate in hospitalized medical patients. J Clin Pharmacol. 1979 Oct;19(10):669-74. doi: 10.1002/j.1552-4604.1979.tb01630.x. No abstract available. |
| 15200658 | Background | Malviya S, Voepel-Lewis T, Tait AR, Reynolds PI, Gujar SK, Gebarski SS, Petter Eldevik O. Pentobarbital vs chloral hydrate for sedation of children undergoing MRI: efficacy and recovery characteristics. Paediatr Anaesth. 2004 Jul;14(7):589-95. doi: 10.1111/j.1460-9592.2004.01243.x. |
| 9351896 | Background | James MO, Cornett R, Yan Z, Henderson GN, Stacpoole PW. Glutathione-dependent conversion to glyoxylate, a major pathway of dichloroacetate biotransformation in hepatic cytosol from humans and rats, is reduced in dichloroacetate-treated rats. Drug Metab Dispos. 1997 Nov;25(11):1223-7. |
| 10471397 | Background | Cornett R, James MO, Henderson GN, Cheung J, Shroads AL, Stacpoole PW. Inhibition of glutathione S-transferase zeta and tyrosine metabolism by dichloroacetate: a potential unifying mechanism for its altered biotransformation and toxicity. Biochem Biophys Res Commun. 1999 Sep 7;262(3):752-6. doi: 10.1006/bbrc.1999.1287. |
| 9531472 | Background | Tong Z, Board PG, Anders MW. Glutathione transferase zeta catalyses the oxygenation of the carcinogen dichloroacetic acid to glyoxylic acid. Biochem J. 1998 Apr 15;331 ( Pt 2)(Pt 2):371-4. doi: 10.1042/bj3310371. |
| 10373324 | Background | Fernandez-Canon JM, Hejna J, Reifsteck C, Olson S, Grompe M. Gene structure, chromosomal location, and expression pattern of maleylacetoacetate isomerase. Genomics. 1999 Jun 15;58(3):263-9. doi: 10.1006/geno.1999.5832. |
| 11692075 | Background | Blackburn AC, Coggan M, Tzeng HF, Lantum H, Polekhina G, Parker MW, Anders MW, Board PG. GSTZ1d: a new allele of glutathione transferase zeta and maleylacetoacetate isomerase. Pharmacogenetics. 2001 Nov;11(8):671-8. doi: 10.1097/00008571-200111000-00005. |
| 10739172 | Background | Blackburn AC, Tzeng HF, Anders MW, Board PG. Discovery of a functional polymorphism in human glutathione transferase zeta by expressed sequence tag database analysis. Pharmacogenetics. 2000 Feb;10(1):49-57. doi: 10.1097/00008571-200002000-00007. |
| 13172552 | Background | MARSHALL EK Jr, OWENS AH Jr. Absorption, excretion and metabolic fate of chloral hydrate and trichloroethanol. Bull Johns Hopkins Hosp. 1954 Jul;95(1):1-18. No abstract available. |
| 6144464 | Background | Jochemsen R, Breimer DD. Pharmacokinetics of benzodiazepines: metabolic pathways and plasma level profiles. Curr Med Res Opin. 1984;8 Suppl 4:60-79. doi: 10.1185/03007998409109545. |
| 9207222 | Background | Henderson GN, Yan Z, James MO, Davydova N, Stacpoole PW. Kinetics and metabolism of chloral hydrate in children: identification of dichloroacetate as a metabolite. Biochem Biophys Res Commun. 1997 Jun 27;235(3):695-8. doi: 10.1006/bbrc.1997.6868. |
| Background | Toxicological review of dichloroacetic acid (CAS No. 79-43-6). U.S. Environ. Protection Agency. Washington, DC, August, 2003. |
| 2219130 | Background | Bull RJ, Sanchez IM, Nelson MA, Larson JL, Lansing AJ. Liver tumor induction in B6C3F1 mice by dichloroacetate and trichloroacetate. Toxicology. 1990 Sep;63(3):341-59. doi: 10.1016/0300-483x(90)90195-m. |
| 1516771 | Background | Daniel FB, DeAngelo AB, Stober JA, Olson GR, Page NP. Hepatocarcinogenicity of chloral hydrate, 2-chloroacetaldehyde, and dichloroacetic acid in the male B6C3F1 mouse. Fundam Appl Toxicol. 1992 Aug;19(2):159-68. doi: 10.1016/0272-0590(92)90147-a. |
| 2055364 | Background | DeAngelo AB, Daniel FB, Stober JA, Olson GR. The carcinogenicity of dichloroacetic acid in the male B6C3F1 mouse. Fundam Appl Toxicol. 1991 Feb;16(2):337-47. doi: 10.1016/0272-0590(91)90118-n. |
| 9097974 | Background | Pereira MA, Li K, Kramer PM. Promotion by mixtures of dichloroacetic acid and trichloroacetic acid of N-methyl-N-nitrosourea-initiated cancer in the liver of female B6C3F1 mice. Cancer Lett. 1997 May 1;115(1):15-23. doi: 10.1016/s0304-3835(97)04699-5. |
| 8603361 | Background | Pereira MA, Phelps JB. Promotion by dichloroacetic acid and trichloroacetic acid of N-methyl-N-nitrosourea-initiated cancer in the liver of female B6C3F1 mice. Cancer Lett. 1996 Apr 19;102(1-2):133-41. doi: 10.1016/0304-3835(96)04156-0. |
| 8980710 | Background | DeAngelo AB, Daniel FB, Most BM, Olson GR. The carcinogenicity of dichloroacetic acid in the male Fischer 344 rat. Toxicology. 1996 Dec 18;114(3):207-21. doi: 10.1016/s0300-483x(96)03510-x. |
| 9544695 | Background | McHugh Law J, Lopez L, DeAngelo AB. Hepatotoxicity of the drinking water disinfection by-product, dichloroacetic acid, in the medaka small fish model. Toxicol Lett. 1998 Jan 16;94(1):19-27. doi: 10.1016/s0378-4274(97)00095-7. |
| 9865481 | Background | Kato-Weinstein J, Lingohr MK, Orner GA, Thrall BD, Bull RJ. Effects of dichloroacetate on glycogen metabolism in B6C3F1 mice. Toxicology. 1998 Sep 15;130(2-3):141-54. doi: 10.1016/s0300-483x(98)00106-1. |
| 9710704 | Background | Stacpoole PW, Henderson GN, Yan Z, Cornett R, James MO. Pharmacokinetics, metabolism and toxicology of dichloroacetate. Drug Metab Rev. 1998 Aug;30(3):499-539. doi: 10.3109/03602539808996323. No abstract available. |
| 2815084 | Background | DeAngelo AB, Daniel FB, McMillan L, Wernsing P, Savage RE Jr. Species and strain sensitivity to the induction of peroxisome proliferation by chloroacetic acids. Toxicol Appl Pharmacol. 1989 Nov;101(2):285-98. doi: 10.1016/0041-008x(89)90277-9. |
| 9736484 | Background | Everhart JL, Kurtz DT, McMillan JM. Dichloroacetic acid induction of peroxisome proliferation in cultured hepatocytes. J Biochem Mol Toxicol. 1998;12(6):351-9. doi: 10.1002/(sici)1099-0461(1998)12:63.0.co;2-2. |
| 9703482 | Background | Zhou YC, Waxman DJ. Activation of peroxisome proliferator-activated receptors by chlorinated hydrocarbons and endogenous steroids. Environ Health Perspect. 1998 Aug;106 Suppl 4(Suppl 4):983-8. doi: 10.1289/ehp.98106s4983. |
| 10581215 | Background | Maloney EK, Waxman DJ. trans-Activation of PPARalpha and PPARgamma by structurally diverse environmental chemicals. Toxicol Appl Pharmacol. 1999 Dec 1;161(2):209-18. doi: 10.1006/taap.1999.8809. |
| 2219131 | Background | Sanchez IM, Bull RJ. Early induction of reparative hyperplasia in the liver of B6C3F1 mice treated with dichloroacetate and trichloroacetate. Toxicology. 1990 Oct;64(1):33-46. doi: 10.1016/0300-483x(90)90097-z. |
| 7641179 | Background | Snyder RD, Pullman J, Carter JH, Carter HW, DeAngelo AB. In vivo administration of dichloroacetic acid suppresses spontaneous apoptosis in murine hepatocytes. Cancer Res. 1995 Sep 1;55(17):3702-5. |
| 11134557 | Background | Lingohr MK, Thrall BD, Bull RJ. Effects of dichloroacetate (DCA) on serum insulin levels and insulin-controlled signaling proteins in livers of male B6C3F1 mice. Toxicol Sci. 2001 Jan;59(1):178-84. doi: 10.1093/toxsci/59.1.178. |
| Background | Gonzalez-Leon A, Schultz IR, Bull RJ. Species differences in the toxicokinetics of dichloroacetate and trichloroacetate in F344 rats and B6C3F1 mice after prolonged administration in drinking water. Fundam Appl Toxicol Suppl 36, Abst. 168, p. 33, 1997. |
| 9344886 | Background | Gonzalez-Leon A, Schultz IR, Xu G, Bull RJ. Pharmacokinetics and metabolism of dichloroacetate in the F344 rat after prior administration in drinking water. Toxicol Appl Pharmacol. 1997 Oct;146(2):189-95. doi: 10.1006/taap.1997.8232. |
| 10462436 | Background | Waxman DJ. P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Arch Biochem Biophys. 1999 Sep 1;369(1):11-23. doi: 10.1006/abbi.1999.1351. |
| 7837977 | Background | DeMarini DM, Perry E, Shelton ML. Dichloroacetic acid and related compounds: induction of prophage in E. coli and mutagenicity and mutation spectra in Salmonella TA100. Mutagenesis. 1994 Sep;9(5):429-37. doi: 10.1093/mutage/9.5.429. |
| 8812237 | Background | Fox AW, Yang X, Murli H, Lawlor TE, Cifone MA, Reno FE. Absence of mutagenic effects of sodium dichloroacetate. Fundam Appl Toxicol. 1996 Jul;32(1):87-95. doi: 10.1006/faat.1996.0110. |
| 8625942 | Background | Fuscoe JC, Afshari AJ, George MH, DeAngelo AB, Tice RR, Salman T, Allen JW. In vivo genotoxicity of dichloroacetic acid: evaluation with the mouse peripheral blood micronucleus assay and the single cell gel assay. Environ Mol Mutagen. 1996;27(1):1-9. doi: 10.1002/(SICI)1098-2280(1996)27:13.0.CO;2-L. |
| 9379909 | Background | Giller S, Le Curieux F, Erb F, Marzin D. Comparative genotoxicity of halogenated acetic acids found in drinking water. Mutagenesis. 1997 Sep;12(5):321-8. doi: 10.1093/mutage/12.5.321. |
| 9651541 | Background | Harrington-Brock K, Doerr CL, Moore MM. Mutagenicity of three disinfection by-products: di- and trichloroacetic acid and chloral hydrate in L5178Y/TK +/- (-)3.7.2C mouse lymphoma cells. Mutat Res. 1998 Mar 30;413(3):265-76. doi: 10.1016/s1383-5718(98)00026-6. |
| 9395208 | Background | Leavitt SA, DeAngelo AB, George MH, Ross JA. Assessment of the mutagenicity of dichloroacetic acid in lacI transgenic B6C3F1 mouse liver. Carcinogenesis. 1997 Nov;18(11):2101-6. doi: 10.1093/carcin/18.11.2101. |
| 6991030 | Background | Rapson WH, Nazar MA, Butsky VV. Mutagenicity produced by aqueous chlorination of organic compounds. Bull Environ Contam Toxicol. 1980 Apr;24(4):590-6. doi: 10.1007/BF01608160. No abstract available. |
| 351387 | Background | Waskell L. A study of the mutagenicity of anesthetics and their metabolites. Mutat Res. 1978 May;57(2):141-53. doi: 10.1016/0027-5107(78)90261-0. |
| 3702676 | Background | Mariash CN, Schwartz HL. Effect of dichloroacetic acid on rat hepatic messenger RNA activity profiles. Metabolism. 1986 May;35(5):452-6. doi: 10.1016/0026-0495(86)90137-x. |
| 3611638 | Background | Barton CH, Bailey E. Changes in immunoreactive malic enzyme in liver and brown adipose tissue during development of the rat. J Dev Physiol. 1987 Jun;9(3):215-24. |
| 9514176 | Background | Barak C, Reed MK, Maniscalco SP, Sherry AD, Malloy CR, Jessen ME. Effects of dichloroacetate on mechanical recovery and oxidation of physiologic substrates after ischemia and reperfusion in the isolated heart. J Cardiovasc Pharmacol. 1998 Mar;31(3):336-44. doi: 10.1097/00005344-199803000-00002. |
| 2318357 | Background | Stacpoole PW, Harwood HJ Jr, Cameron DF, Curry SH, Samuelson DA, Cornwell PE, Sauberlich HE. Chronic toxicity of dichloroacetate: possible relation to thiamine deficiency in rats. Fundam Appl Toxicol. 1990 Feb;14(2):327-37. doi: 10.1016/0272-0590(90)90212-3. |
| 3827895 | Background | Hong JY, Pan JM, Gonzalez FJ, Gelboin HV, Yang CS. The induction of a specific form of cytochrome P-450 (P-450j) by fasting. Biochem Biophys Res Commun. 1987 Feb 13;142(3):1077-83. doi: 10.1016/0006-291x(87)91525-7. |
| 2306264 | Background | Yoo JS, Park HS, Ning SM, Lee MJ, Yang CS. Effects of thiamine deficiency on hepatic cytochromes P450 and drug-metabolizing enzyme activities. Biochem Pharmacol. 1990 Feb 1;39(3):519-25. doi: 10.1016/0006-2952(90)90059-t. |
| 8975762 | Background | Yang HM, Houser WH, Davis ME. Dichloroacetic acid treatment increases hepatic CYP2E1 in male and female rats. Toxicol Appl Pharmacol. 1996 Dec;141(2):382-8. doi: 10.1006/taap.1996.0303. |
| 11470764 | Background | Thai SF, Allen JW, DeAngelo AB, George MH, Fuscoe JC. Detection of early gene expression changes by differential display in the livers of mice exposed to dichloroacetic acid. Carcinogenesis. 2001 Aug;22(8):1317-22. doi: 10.1093/carcin/22.8.1317. |
| Background | NTP Technical Report. Toxicology and carcinogenesis study of chloral hydrate. NIH Publication No. 03-4437, 2002. |
| Background | IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Chloral hydrate. World Health Organization, 2004, pp. 317-358. |
| 1802654 | Background | Davidson IW, Beliles RP. Consideration of the target organ toxicity of trichloroethylene in terms of metabolite toxicity and pharmacokinetics. Drug Metab Rev. 1991;23(5-6):493-599. doi: 10.3109/03602539109029772. |
| 15507380 | Background | Ikbal M, Tastekin A, Dogan H, Pirim I, Ors R. The assessment of genotoxic effects in lymphocyte cultures of infants treated with chloral hydrate. Mutat Res. 2004 Dec 12;564(2):159-64. doi: 10.1016/j.mrgentox.2004.08.007. |
| 12659714 | Background | Ho YS, Ma HY, Chang HY, Wei BL, Lee CC, Ho SY, Guo HR, Wu TP, Chang WH, Wang YJ. Lipid peroxidation and cell death mechanisms in rats and human cells induced by chloral hydrate. Food Chem Toxicol. 2003 May;41(5):621-9. doi: 10.1016/s0278-6915(02)00323-x. |
| 14996553 | Background | Harinath S, Sikdar SK. Trichloroethanol enhances the activity of recombinant human TREK-1 and TRAAK channels. Neuropharmacology. 2004 Apr;46(5):750-60. doi: 10.1016/j.neuropharm.2003.11.023. |
| 12694404 | Background | Fischer W, Wirkner K, Weber M, Eberts C, Koles L, Reinhardt R, Franke H, Allgaier C, Gillen C, Illes P. Characterization of P2X3, P2Y1 and P2Y4 receptors in cultured HEK293-hP2X3 cells and their inhibition by ethanol and trichloroethanol. J Neurochem. 2003 May;85(3):779-90. doi: 10.1046/j.1471-4159.2003.01716.x. |
| 12749985 | Background | Sabeti J, Gerhardt GA, Zahniser NR. Chloral hydrate and ethanol, but not urethane, alter the clearance of exogenous dopamine recorded by chronoamperometry in striatum of unrestrained rats. Neurosci Lett. 2003 May 29;343(1):9-12. doi: 10.1016/s0304-3940(03)00301-x. |
| 15447660 | Background | Akundi RS, Macho A, Munoz E, Lieb K, Bringmann G, Clement HW, Hull M, Fiebich BL. 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline-induced apoptosis in the human neuroblastoma cell line SK-N-SH. J Neurochem. 2004 Oct;91(2):263-73. doi: 10.1111/j.1471-4159.2004.02710.x. |
| 8236248 | Background | Templin MV, Parker JC, Bull RJ. Relative formation of dichloroacetate and trichloroacetate from trichloroethylene in male B6C3F1 mice. Toxicol Appl Pharmacol. 1993 Nov;123(1):1-8. doi: 10.1006/taap.1993.1214. |
| 8795309 | Background | Gribble GW. Naturally occurring organohalogen compounds--a comprehensive survey. Fortschr Chem Org Naturst. 1996;68:1-423. No abstract available. |
| 12723459 | Background | Agbenyega T, Planche T, Bedu-Addo G, Ansong D, Owusu-Ofori A, Bhattaram VA, Nagaraja NV, Shroads AL, Henderson GN, Hutson AD, Derendorf H, Krishna S, Stacpoole PW. Population kinetics, efficacy, and safety of dichloroacetate for lactic acidosis due to severe malaria in children. J Clin Pharmacol. 2003 Apr;43(4):386-96. doi: 10.1177/0091270003251392. |
| 9448064 | Background | Yan Z, Henderson GN, James MO, Stacpoole PW. Determination of dichloroacetate and its metabolites in human plasma by gas chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl. 1997 Dec 5;703(1-2):75-84. doi: 10.1016/s0378-4347(97)00404-0. |
| 14632119 | Background | Jia M, Wu WW, Yost RA, Chadik PA, Stacpoole PW, Henderson GN. Simultaneous determination of trace levels of nine haloacetic acids in biological samples as their pentafluorobenzyl derivatives by gas chromatography/tandem mass spectrometry in electron capture negative ion chemical ionization mode. Anal Chem. 2003 Aug 15;75(16):4065-80. doi: 10.1021/ac034036w. |
| 215910 | Background | Stacpoole PW, Moore GW, Kornhauser DM. Toxicity of chronic dichloroacetate. N Engl J Med. 1979 Feb 15;300(7):372. doi: 10.1056/NEJM197902153000726. No abstract available. |
| 9496194 | Background | Stacpoole PW, Barnes CL, Hurbanis MD, Cannon SL, Kerr DS. Treatment of congenital lactic acidosis with dichloroacetate. Arch Dis Child. 1997 Dec;77(6):535-41. doi: 10.1136/adc.77.6.535. No abstract available. |
| 6877297 | Background | Stacpoole PW, Harman EM, Curry SH, Baumgartner TG, Misbin RI. Treatment of lactic acidosis with dichloroacetate. N Engl J Med. 1983 Aug 18;309(7):390-6. doi: 10.1056/NEJM198308183090702. |
| 625308 | Background | Stacpoole PW, Moore GW, Kornhauser DM. Metabolic effects of dichloroacetate in patients with diabetes mellitus and hyperlipoproteinemia. N Engl J Med. 1978 Mar 9;298(10):526-30. doi: 10.1056/NEJM197803092981002. |
| 11774096 | Background | Neiberger RE, George JC, Perkins LA, Theriaque DW, Hutson AD, Stacpoole PW. Renal manifestations of congenital lactic acidosis. Am J Kidney Dis. 2002 Jan;39(1):12-23. doi: 10.1053/ajkd.2002.29872. |
| 14599561 | Background | Ammini CV, Fernandez-Canon J, Shroads AL, Cornett R, Cheung J, James MO, Henderson GN, Grompe M, Stacpoole PW. Pharmacologic or genetic ablation of maleylacetoacetate isomerase increases levels of toxic tyrosine catabolites in rodents. Biochem Pharmacol. 2003 Nov 15;66(10):2029-38. doi: 10.1016/j.bcp.2003.07.002. |
| 16199472 | Background | Guo X, Dixit V, Liu H, Shroads AL, Henderson GN, James MO, Stacpoole PW. Inhibition and recovery of rat hepatic glutathione S-transferase zeta and alteration of tyrosine metabolism following dichloroacetate exposure and withdrawal. Drug Metab Dispos. 2006 Jan;34(1):36-42. doi: 10.1124/dmd.105.003996. Epub 2005 Sep 30. |
| 9728331 | Background | Holme E, Lindstedt S. Tyrosinaemia type I and NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione). J Inherit Metab Dis. 1998 Aug;21(5):507-17. doi: 10.1023/a:1005410820201. |
| 6743680 | Background | Fujita H, Koizumi A, Yamamoto M, Kumai M, Sadamoto T, Ikeda M. Inhibition of delta-aminolevulinate dehydratase in trichloroethylene-exposed rats, and the effects on heme regulation. Biochim Biophys Acta. 1984 Jul 16;800(1):1-10. doi: 10.1016/0304-4165(84)90087-4. |
| 9728332 | Background | Grompe M, Overturf K, al-Dhalimy M, Finegold M. Therapeutic trials in the murine model of hereditary tyrosinaemia type I: a progress report. J Inherit Metab Dis. 1998 Aug;21(5):518-31. doi: 10.1023/a:1005462804271. |
| 7545495 | Background | Grompe M, Lindstedt S, al-Dhalimy M, Kennaway NG, Papaconstantinou J, Torres-Ramos CA, Ou CN, Finegold M. Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type I. Nat Genet. 1995 Aug;10(4):453-60. doi: 10.1038/ng0895-453. |
| 12052898 | Background | Fernandez-Canon JM, Baetscher MW, Finegold M, Burlingame T, Gibson KM, Grompe M. Maleylacetoacetate isomerase (MAAI/GSTZ)-deficient mice reveal a glutathione-dependent nonenzymatic bypass in tyrosine catabolism. Mol Cell Biol. 2002 Jul;22(13):4943-51. doi: 10.1128/MCB.22.13.4943-4951.2002. |
| 15261808 | Background | Shroads AL, Henderson GN, Cheung J, James MO, Stacpoole PW. Unified gas chromatographic-mass spectrometric method for quantitating tyrosine metabolites in urine and plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Sep 5;808(2):153-61. doi: 10.1016/j.jchromb.2004.05.005. |
| 15530481 | Background | Felitsyn NM, Henderson GN, James MO, Stacpoole PW. Liquid chromatography-tandem mass spectrometry method for the simultaneous determination of delta-ALA, tyrosine and creatinine in biological fluids. Clin Chim Acta. 2004 Dec;350(1-2):219-30. doi: 10.1016/j.cccn.2004.08.009. |
| 10775321 | Background | Tzeng HF, Blackburn AC, Board PG, Anders MW. Polymorphism- and species-dependent inactivation of glutathione transferase zeta by dichloroacetate. Chem Res Toxicol. 2000 Apr;13(4):231-6. doi: 10.1021/tx990175q. |
| 12437329 | Background | Anderson WB, Liebler DC, Board PG, Anders MW. Mass spectral characterization of dichloroacetic acid-modified human glutathione transferase zeta. Chem Res Toxicol. 2002 Nov;15(11):1387-97. doi: 10.1021/tx025553x. |
| 15144222 | Background | Anderson WB, Board PG, Anders MW. Glutathione transferase zeta-catalyzed bioactivation of dichloroacetic acid: reaction of glyoxylate with amino acid nucleophiles. Chem Res Toxicol. 2004 May;17(5):650-62. doi: 10.1021/tx034099+. |
| Background | Kinter M, Sherman NE. Peptide Sequencng andIdentifcation Using Tandem Mass Specrometry. John Wiley and Sons, Inc., pp. 147-165, 2000. |
| 9177686 | Background | Cohen SL, Chait BT. Mass spectrometry of whole proteins eluted from sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels. Anal Biochem. 1997 May 1;247(2):257-67. doi: 10.1006/abio.1997.2072. |
| 14637371 | Background | LoPachin RM, Jones RC, Patterson TA, Slikker W Jr, Barber DS. Application of proteomics to the study of molecular mechanisms in neurotoxicology. Neurotoxicology. 2003 Dec;24(6):761-75. doi: 10.1016/j.neuro.2003.08.003. |
| 12747583 | Background | Righetti PG, Castagna A, Antonucci F, Piubelli C, Cecconi D, Campostrini N, Zanusso G, Monaco S. The proteome: anno Domini 2002. Clin Chem Lab Med. 2003 Apr;41(4):425-38. doi: 10.1515/CCLM.2003.065. |
| 10504701 | Background | Gygi SP, Rist B, Gerber SA, Turecek F, Gelb MH, Aebersold R. Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol. 1999 Oct;17(10):994-9. doi: 10.1038/13690. |
| Background | Proteome Research: mass spectrometry. Peter James. Springer, pp. 5-9 2001. |
| 14502116 | Background | Nguyen MH, Keeffe EB. Chronic hepatitis B and hepatitis C in Asian Americans. Rev Gastroenterol Disord. 2003 Summer;3(3):125-34. |
| 12112620 | Background | Mortazavi B, Chanton JP. A rapid and precise technique for measuring delta(13)C-CO(2) and delta(18)O-CO(2) ratios at ambient CO(2) concentrations for biological applications and the influence of container type and storage time on the sample isotope ratios. Rapid Commun Mass Spectrom. 2002;16(14):1398-403. doi: 10.1002/rcm.730. |
| 11156611 | Background | Ronaghi M. Pyrosequencing sheds light on DNA sequencing. Genome Res. 2001 Jan;11(1):3-11. doi: 10.1101/gr.11.1.3. |
| 11546976 | Background | Ritz MA, Fraser R, Edwards N, Di Matteo AC, Chapman M, Butler R, Cmielewski P, Tournadre JP, Davidson G, Dent J. Delayed gastric emptying in ventilated critically ill patients: measurement by 13 C-octanoic acid breath test. Crit Care Med. 2001 Sep;29(9):1744-9. doi: 10.1097/00003246-200109000-00015. |
| 1435883 | Background | Stacpoole PW, Wright EC, Baumgartner TG, Bersin RM, Buchalter S, Curry SH, Duncan CA, Harman EM, Henderson GN, Jenkinson S, et al. A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group. N Engl J Med. 1992 Nov 26;327(22):1564-9. doi: 10.1056/NEJM199211263272204. |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
| Secondary | 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. | No statistical analysis. The data was incomplete and was not analyzed. | Posted | one week |
|
|
| 0 |
| 2 |
| 2 |
| 2 |
| syncope | Nervous system disorders | Systematic Assessment | Patient fainted for 15 seconds when blood was drawn |
|
Not provided
Not provided
| D009930 |
| Organic Chemicals |
| D006843 | Hydrocarbons, Chlorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D000597 | Amino Acids, Branched-Chain |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000601 | Amino Acids, Essential |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D055614 | Genetic Phenomena |
| D040481 | Genome Components |
| D016678 | Genome |
| D040342 | Genetic Structures |