Farmakotoksikologi af trichlorethylenmetabolitter
2. juni 2015 opdateret af: University of Florida
Farmakotoksikologi af trichlorethylenmetabolitter: kortsigtet effekt af DCA på in vivo tyrosinkatabolisme og MAAI-ekspression
Dette projekt fokuserer på kinetikken, metabolismen og human toksikologi af dichloracetat (DCA) og tyrosin katabolisme.
Hypotesen er, at tyrosinmetabolismen vil være størst hos personer, der har KRT-varianten for GSTz1/MAAI, for hvilken DCA udviser en høj Km.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Specifikt formål 4. Kvantificere effekterne af DCA på human tyrosinmetabolisme og på dets egen biotransformation i forhold til dosis og genotype.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
2
Fase
- Ikke anvendelig
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Florida
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Gainesville, Florida, Forenede Stater, 32610
- University of Florida
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
22 år til 60 år (Voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inklusionskriterier:
- Voksne, der er planlagt til elektiv kirurgi for godartet leversygdom.
- Normal EKG og historie
- Normale baseline laboratorier
Ekskluderingskriterier:
- Graviditet
- svær anæmi, defineret som en hæmatokrit < 30 %.
- diabetes mellitus
- nyreinsufficiens, defineret som serumkreatinin > 1,5 mg/dl eller kreatininclearance < 60 ml/min.
- forhøjede leverenzymer
- psykiatrisk sygdom, der kræver medicin
- primær biliær cirrhose eller enhver anden form for cirrhose
- viral hepatitis eller ikke-viral steatohepatitis
- koronar hjertesygdom, defineret som kræver daglig administration af anti-anginal medicin eller som New York Heart Association klasse III eller IV hjertesvigt
- malignitet af enhver type på ethvert anatomisk sted
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Grundvidenskab
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Haplotyper og DCA-metabolisme
Raske mænd og kvinder med forskellige haplotyper vil modtage en infusion af leucin og tyrosin.
Den følgende dag begynder de en 5-dages kur med dichloracetat (DCA) i en dosis på 2,5 mcg/kg/dag.
På dag 6 vender de tilbage og får endnu en infusion af leucin og tyrosin.
Efter en udvaskningsperiode på 30 dage vender individet tilbage og modtager igen en infusion af leucin og tyrosin.
Derefter på dag 2 begynder de en dosis af DCA ved 25 mg/kg i 5 dage og vender derefter tilbage til den sidste infusion af leucin og tyrosin.
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Raske mænd og kvinder med forskellige haplotyper vil modtage en infusion af leucin og tyrosin.
Den følgende dag begynder de en 5-dages kur med dichloracetat (DCA) i en dosis på 2,5 mcg/kg/dag.
På dag 6 vender de tilbage og får endnu en infusion af leucin og tyrosin.
Efter en udvaskningsperiode på 30 dage vender individet tilbage og modtager igen en infusion af leucin og tyrosin.
Derefter på dag 2 begynder de en dosis DCA på 25 mg/kg i 5 dage og vender derefter tilbage til den sidste infusion af leucin og tyrosin.
Andre navne:
Forsøgspersonerne vil få udtaget 5 ml blod til genotypebestemmelse
Andre navne:
Raske mænd og kvinder med forskellige haplotyper vil modtage en infusion af leucin og tyrosin.
Den følgende dag begynder de en 5-dages kur med dichloracetat (DCA) i en dosis på 2,5 mcg/kg/dag.
På dag 6 vender de tilbage og får endnu en infusion af leucin og tyrosin.
Efter en udvaskningsperiode på 30 dage vender individet tilbage og modtager igen en infusion af leucin og tyrosin.
Derefter på dag 2 begynder de en dosis DCA på 25 mg/kg i 5 dage og vender derefter tilbage til den sidste infusion af leucin og tyrosin.
Andre navne:
Raske mænd og kvinder med forskellige haplotyper vil modtage en infusion af leucin og tyrosin.
Den følgende dag begynder de en 5-dages kur med dichloracetat (DCA) i en dosis på 2,5 mcg/kg/dag.
På dag 6 vender de tilbage og får endnu en infusion af leucin og tyrosin.
Efter en udvaskningsperiode på 30 dage vender individet tilbage og modtager igen en infusion af leucin og tyrosin.
Derefter på dag 2 begynder de en dosis af DCA ved 25 mg/kg i 5 dage og vender derefter tilbage til den sidste infusion af leucin og tyrosin.
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Interaktionen mellem DCA og/eller tyrosinnedbrydningsprodukter og maleylacetoacetat-isomerase (MAAI) in Vivo.
Tidsramme: En uge
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Forsøgspersonerne får en infusion af aminosyrerne leucin og tyrosin. Næste dag starter de en fem-dages kur med dichloracetat (DCA). Efter fem dage får de endnu en infusion af tyrosin og leucin. Farmakokinetikken af DCA beregnes efter den anden infusion. |
En uge
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Hæmning af tyrosin og individets haplotype
Tidsramme: en uge
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Givet infusionen af ovennævnte aminosyrer og DCA-administration vil inhiberingen af tyrosin blive målt i KRT-haplotypen og ikke-KRT-haplotypen.
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en uge
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Ledende efterforsker: Peter W Stacpoole, PhD, MD, University of Florida
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
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- 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.
- 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.
- 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.
- 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.
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Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. august 2011
Primær færdiggørelse (Faktiske)
1. januar 2012
Studieafslutning (Faktiske)
1. januar 2012
Datoer for studieregistrering
Først indsendt
17. marts 2009
Først indsendt, der opfyldte QC-kriterier
18. marts 2009
Først opslået (Skøn)
19. marts 2009
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
3. juni 2015
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
2. juni 2015
Sidst verificeret
1. juli 2013
Mere information
Begreber relateret til denne undersøgelse
Andre undersøgelses-id-numre
- 14617-CP-001
- 5R01ES014617 (U.S. NIH-bevilling/kontrakt)
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