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Adenosylmethionine Metabolism in Human Inflammation

6 augustus 2015 bijgewerkt door: En-Pei Isabel Chiang, National Chung Hsing University

Translational Study on the Regulation of Adenosylmethionine Synthesis During Chronic Inflammation

The investigators propose to conduct a translational study on the regulation of S-adenosylmethionine synthesis and cellular methylation reactions during chronic inflammation. Development of in vitro cell models may reveal the regulatory mechanisms by which specific inflammatory mediators cause metabolic changes and alter DNA methylation status. Metabolic and pharmacological studies in the in vivo models will enable us to better understand the regulation of inter-organ homeostasis of S-adenosyl methionine and help identify tissue specific biomarkers for methylation and epigenetic modifications in different stage of chronic inflammation. The clinical study in human subjects will help distinguish the impacts of autoimmune rheumatic disease, degenerated joint disease, or specific medication use on significant clinical and biochemical markers in folate and vitamin B6 metabolic pathways.The Investigators hope the present study can identify specific clinical markers for potential epigenetic changes in patients suffering from chronic inflammation, which will contribute to better clinical management of these diseases in humans.

Studie Overzicht

Toestand

Onbekend

Conditie

Gedetailleerde beschrijving

The significance of epigenetic alterations in autoimmune rheumatic diseases and degenerated joint diseases has drawn great attention among clinicians and researchers. Aberrant methylation status has been demonstrated in human chronic inflammation yet more efforts have focused on global and sequence-specific hypomethylation and overexpression of specific genes. Few studies investigated the regulation of S-adenosylmethionine homeostasis and regulation during inflammation. At present the relevance and regulation of the complex epigenetic profiles and their modifications among different tissues and organs during inflammation remain largely unknown.

Studietype

Observationeel

Inschrijving (Verwacht)

250

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 80 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Bemonsteringsmethode

Kanssteekproef

Studie Bevolking

patients with arthritis or healthy adults

Beschrijving

Inclusion Criteria:

> 18 years

Exclusion Criteria:

pregnancy,
anemia (hemoglobin 10 mg/dL or lower),
thrombocytopenia (platelet count below 50,000 cells/μL),
abnormal serum hepatic transaminase (aspartate aminotransferase or alanine aminotransferase above 50 IU/L),
diabetes or cancer

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Aantal groepen / cohorten

Cohorten en interventies

Groep / Cohort
Arthritis subjects with arthritis
Health control subjects Health control

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat	Maatregel Beschrijving	Tijdsspanne
s-adenosylmethionine Tijdsspanne: Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor	blood samples were collected and stored for later analyses of above metabolites	Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor
homocysteine Tijdsspanne: Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor	blood samples were collected and stored for later analyses of above metabolites	Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor
folate Tijdsspanne: Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor	blood samples were collected and stored for later analyses of above metabolites	Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor
vitamin B6 Tijdsspanne: Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor	blood samples were collected and stored for later analyses of above metabolites	Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor

Secundaire uitkomstmaten

Uitkomstmaat	Maatregel Beschrijving	Tijdsspanne
blood amino acid profile (serine, glycine, methionine,cysteine, cystathionine, dimethylglycine) Tijdsspanne: Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor	blood samples were collected and stored for later analyses of above metabolites	Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor
gene expression of target enzymes in PBMCs Tijdsspanne: Blood were collected at admission.Blood were dawn again 1mo later if his medication was changed by the doctor	blood samples were collected and stored for later analyses	Blood were collected at admission.Blood were dawn again 1mo later if his medication was changed by the doctor
enzyme activities of S-adenosylmethionine synthase in RBC Tijdsspanne: Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor	blood samples were collected and stored for later analyses of above metabolites	Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor
vitamin B6 metabolic enzyme in RBC Tijdsspanne: Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor	blood samples were collected and stored for later analyses of above metabolites	Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor
polymorphisms in one carbon metabolism enzymes in PBMCs Tijdsspanne: Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor	blood samples were collected and stored for later analyses	Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

National Chung Hsing University

Medewerkers

National Science Council, Taiwan

Ministry of Science and Technology, Taiwan

Onderzoekers

Hoofdonderzoeker: En-Pei I Chiang, PhD, Department of Food Science and Biotechnology, National Chung Hsing University

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 januari 2011

Primaire voltooiing (Werkelijk)

1 juli 2014

Studie voltooiing (Verwacht)

1 augustus 2015

Studieregistratiedata

Eerst ingediend

28 juli 2015

Eerst ingediend dat voldeed aan de QC-criteria

6 augustus 2015

Eerst geplaatst (Schatting)

11 augustus 2015

Updates van studierecords

Laatste update geplaatst (Schatting)