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Adenosylmethionine Metabolism in Human Inflammation

6 août 2015 mis à jour par: 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.

Aperçu de l'étude

Statut

Inconnue

Les conditions

Description détaillée

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.

Type d'étude

Observationnel

Inscription (Anticipé)

250

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 80 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

Méthode d'échantillonnage

Échantillon de probabilité

Population étudiée

patients with arthritis or healthy adults

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Nombre de groupes / cohortes

Cohortes et interventions

Groupe / Cohorte
Arthritis subjects with arthritis
Health control subjects Health control

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats	Description de la mesure	Délai
s-adenosylmethionine Délai: 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 Délai: 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 Délai: 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 Délai: 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

Mesures de résultats secondaires

Mesure des résultats	Description de la mesure	Délai
blood amino acid profile (serine, glycine, methionine,cysteine, cystathionine, dimethylglycine) Délai: 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 Délai: 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 Délai: 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 Délai: 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 Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

National Chung Hsing University

Collaborateurs

National Science Council, Taiwan

Ministry of Science and Technology, Taiwan

Les enquêteurs

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

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 janvier 2011

Achèvement primaire (Réel)

1 juillet 2014

Achèvement de l'étude (Anticipé)

1 août 2015

Dates d'inscription aux études

Première soumission

28 juillet 2015

Première soumission répondant aux critères de contrôle qualité

6 août 2015

Première publication (Estimation)

11 août 2015

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

11 août 2015

Dernière mise à jour soumise répondant aux critères de contrôle qualité