Clinical trial NCT02520206: Adenosylmethionine Metabolism in Human Inflammation
Official title: Translational Study on the Regulation of Adenosylmethionine Synthesis During Chronic Inflammation
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Arthritis
Chronic Inflammation
Lead sponsor: National Chung Hsing University
Sponsor class: OTHER
Collaborators: name: National Science and Technology Council, Taiwan
name: Ministry of Science and Technology, Taiwan
First posted: 2015-08-11
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Sampling method: PROBABILITY_SAMPLE
Study population: patients with arthritis or healthy adults

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: s-adenosylmethionine
timeFrame: Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor
measure: homocysteine
timeFrame: Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor
measure: folate
timeFrame: Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor
measure: vitamin B6
timeFrame: Blood were collected at admission. Some participants were followed for 4wks if medication was changed by the doctor
Secondary outcomes:
measure: blood amino acid profile (serine, glycine, methionine,cysteine, cystathionine, dimethylglycine)
timeFrame: Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor
measure: gene expression of target enzymes in PBMCs
timeFrame: Blood were collected at admission.Blood were dawn again 1mo later if his medication was changed by the doctor
measure: enzyme activities of S-adenosylmethionine synthase in RBC
timeFrame: Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor
measure: vitamin B6 metabolic enzyme in RBC
timeFrame: Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor
measure: polymorphisms in one carbon metabolism enzymes in PBMCs
timeFrame: Blood were collected at admission. Blood were dawn again 1mo later if his medication was changed by the doctor
Other outcomes:
Locations:
Study officials:
affiliation: Department of Food Science and Biotechnology, National Chung Hsing University
name: En-Pei I Chiang, PhD
role: PRINCIPAL_INVESTIGATOR
References: