Changes of Muramyl Dipeptide in Intestinal and Extra-intestinal Diseases

A Bacterial Bi-functional Peptidoglycan Hydrolase Sheds NOD2 Ligands to Regulate Gut Homeostasis

Nucleotide-binding oligomerization domain 2 (Nod2) signaling is critical for human health.To figure out the clinical relevance of NOD2 ligands, the investigators plan to evaluate the change of NOD2 ligands in inflammatory bowel diseases (IBD), CRC, atherosclerotic cardiovascular disease (ACVD), and type 2 diabetes mellitus (DM2 ).

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Inflammatory Bowel Disease; Type2 Diabetes Mellitus; Atherosclerotic Cardiovascular Disease
• Intervention / Treatment: Other: Observational studies, no intervention

Detailed Description

Previous studies have shown that NOD2 gene mutants were associated with the Crohn's disease (CD), colorectal cancer (CRC) and many other diseases, suggesting the critical role of NOD2 signaling in human physiology and pathogenethesis. However, whether decreased NOD2 ligands also contributed to these diseases is unknown. In this study, the investigators plan to evaluate the change of NOD2 ligands in inflammatory bowel diseases (IBD), CRC, atherosclerotic cardiovascular disease (ACVD), and type 2 diabetes mellitus (DM2 ). For each of the patient, a sex- and age- matched control were chosen. Both the targeted metabolomics (LC-MS-MS methods) and NOD2-transfected cells co-expressing NF-κB luciferase reporters were used to test NOD2 ligands in the fecal and plasma samples.

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

• Study Contact: Name: Jie Gao, PHD; Phone Number: 86 15625043043; Email: 994856235@qq.com

Study Locations

• China
  • Guang Dong
    • Guangzhou, Guang Dong, China, 510000
      • Recruiting
      • Zhujiang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All the patients with IBD, CRC, ACVD or DM2 hospitalized in Zhujiang hospital will be eligible to be enrolled. Also, their age- and sex- matched healthy controls making a physical examination in Zhujiang hospital will be eligible to be enrolled

Description

Inclusion Criteria:

1. Males or females at least 18-70 years old.
2. Patient able to give informed consent.
3. Patient with biopsy-proven CRC
4. Patient with biopsy-proven Crohn's disease (CD) or ulcerative colitis(UC), in the active phase.
5. patients with clinical diagnosed DM2
6. patients with ACVD:coronary angiography more than 50% stenosis in single or multiple vessels.
7. The age- and sex- matched health controls for each patient.

Exclusion Criteria:

1.Use antibiotics or probiotics within the last 2 weeks.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Crohn's disease; The fecal and plasma were collected	Other: Observational studies, no intervention; Observational studies, no intervention
Ulcerative colitis; The fecal and plasma were collected	Other: Observational studies, no intervention; Observational studies, no intervention
Diabetes mellitus, type 2; The fecal and plasma were collected	Other: Observational studies, no intervention; Observational studies, no intervention
Atherosclerotic cardiovascular disease; The fecal and plasma were collected	Other: Observational studies, no intervention; Observational studies, no intervention
Colorectal cancer; The fecal and plasma were collected	Other: Observational studies, no intervention; Observational studies, no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NOD2 ligands in fecal and plasma	detected using targeted metabolomics (LC-MS-MS methods) and NOD2-transfected cells co-expressing NF-κB luciferase reporters	baseline

Collaborators and Investigators

• Sponsor: Zhujiang Hospital
• Collaborators: National Natural Science Foundation of China
• Investigators: Principal Investigator: Hongwei Zhou, professor, Zhujiang Hospital, Guangzhou, Guangdong

Publications and helpful links

General Publications

• Philpott DJ, Sorbara MT, Robertson SJ, Croitoru K, Girardin SE. NOD proteins: regulators of inflammation in health and disease. Nat Rev Immunol. 2014 Jan;14(1):9-23. doi: 10.1038/nri3565. Epub 2013 Dec 13. Erratum In: Nat Rev Immunol. 2014 Feb;14(2):131.

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2020
• Primary Completion (Anticipated): June 10, 2023
• Study Completion (Anticipated): August 15, 2023

Study Registration Dates

• First Submitted: June 7, 2021
• First Submitted That Met QC Criteria: June 10, 2021
• First Posted (Actual): June 14, 2021

Study Record Updates

• Last Update Posted (Actual): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 10, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: NOD2 ligands
• Additional Relevant MeSH Terms: Digestive System Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Endocrine System Diseases; Gastrointestinal Diseases; Diabetes Mellitus; Gastroenteritis; Intestinal Diseases; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Inflammatory Bowel Diseases; Atherosclerosis
• Other Study ID Numbers: ZhujiangH-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No