Response of Gut Microbiota in Type 2 Diabetes to Hypoglycemic Agents

Type2 Diabetes Mellitus Clinical Trial

Official title:

Response of Gut Microbiota in Type 2 Diabetes to Hypoglycemic Agents

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04287387
• Other study ID #: APIMCAS2018001
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: March 2, 2020
• Est. completion date: March 2, 2021

Study information

• Verified date: February 2020
• Source: Peking Union Medical College Hospital
• Contact: Weigang zhao, MD
• Phone: +86 69151876
• Email: xiehezhaoweigang[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Intestinal microflora refers to the trillions of microorganisms living in our gut, which is considered as an independent endocrine organ of human body. Intestinal microbiota plays a very important role in human health. The composition of human intestinal microbiota is affected by a variety of factors, including age, living region, eating habits, nutrition, probiotics, antibiotics and so on. It is found that the imbalance of intestinal microbiota is closely related to the occurrence and development of metabolic diseases including type 2 diabetes mellitus (T2DM). There are great differences in the structure and function of intestinal microbiota between healthy people and T2DM patients, and recently changes of intestinal microbiota have been observed in pre-diabetes. In recent years, it has been found that some commonly used hypoglycemic drugs may regulate and improve the imbalance of intestinal flora of T2DM patients, including metformin, α - glucosidase inhibitor, and Glucagon-like peptide-1(GLP-1) receptor agonist, which have a positive impact on the short chain fatty acid (SCFAs) producing bacteria. However, on the one hand, subjects of those studies were mostly western population and there were just a few studies on the influence of anti-diabetic drug on human gut microbiota in Chinese population, on the other hand, the study of influence of Dipeptidyl peptidase-4(DPP-4) inhibitors, sulfonylureas, sodium-dependent glucose transporters-2(SGLT-2) inhibitors or thiazolidinediones on intestinal microbiota is rare or even absent. This study aims to explore the effect of different hypoglycemic drugs on intestinal flora and find the potential intestinal target of drug action in Chinese population.

Description:

In this study, T2DM patients who were free of anti-diabetic drugs or those have taken hypoglycemic drugs and ready to add a new drug were recruited, they were treated with metformin, α - glucosidase inhibitor, DPP-4 inhibitors, sulfonylureas, SGLT-2 inhibitors, or thiazolidinediones according to their state of illness. Faecal specimen will be collected for test of composition of gut microbiota at baseline and 4-week, 8-week，12-week after taking medication. At baseline, patients will take physical examination and blood test, every patient will complete the questionnaire under the direction of doctors to get their general information and diet habits. Physical examination and blood test will repeat at 4-week, 8-week，12-week after treatment.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 180
• Est. completion date: March 2, 2021
• Est. primary completion date: March 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• According to the diagnostic criteria of World Health Organization (WHO) in 1999, type 2 diabetes mellitus was diagnosed clinically

• The age ranged from 18 to 65 years (including 18 and 65 years)

• Free of hypoglycemic drugs in the past 3 months; or have taken hypoglycemic drugs, and other hypoglycemic drugs need to be added at present.

• Sign written consent form voluntarily

Exclusion Criteria:

• Other types of diabetes mellitus

• At least in the last 1 month, no antibiotics or microbial agents have been used

• History of infectious diseases such as tuberculosis, viral hepatitis, HIV, and periodontal disease; history of dental disease

• Acute complications of diabetes mellitus within 6 months

• History of myocardial infarction or stroke within 6 months, or existing severe cardiovascular disease and risk

• Abnormal liver function [i.e. serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is 1.5 times higher than the upper limit of normal value];Abnormal renal function [glomerular filtration rate=60 ml/min]

• Severe hypertension that defined as systolic blood pressure =160 mmHg, diastolic blood pressure =90 mmHg with drug therapy, or hypotension (resting seat blood pressure < 90/50 mmHg)

• History of acute and chronic gastroenteritis or gastrointestinal surgery

• psychosis, alcohol dependence or history of drug abuse, lactation women, participation in other studies three months before the trial, allergic constitution or allergic to a variety of drug and those researchers think inappropriate to the research.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type2 Diabetes Mellitus

Intervention

Drug:
• Glucophage 500Mg Tablet
0.5g three times daily
• Acarbose Tablets
50mg three times daily
• Sitagliptin tablet
100mg once daily
• Dapagliflozin Tablet
10mg once daily
• Pioglitazone Tablets
30mg once daily
• Glimepiride Tablets
2mg once daily

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital	Chinese Academy of Sciences

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes from baseline to post-treatment in composition in gut microbiota analyzed by meta-genome sequencing.		Baseline, Week 4, Week 8, Week 12
Primary	Changes from baseline to post-treatment in composition in fasting blood glucose.		Baseline, Week 4, Week 8, Week 12
Primary	Changes from baseline to post-treatment in composition in level of TNF-a.		Baseline, Week 4, Week 8, Week 12
Primary	Changes from baseline to post-treatment in composition in fasting insulin.		Baseline, Week 4, Week 8, Week 12
Primary	Changes from baseline to post-treatment in blood lipid including cholesterol, triglycerides, high-density lipoprotein.		Baseline, Week 4, Week 8, Week 12
Primary	Changes from baseline to post-treatment in composition in 2-hour postprandial blood glucose.		Baseline, Week 4, Week 8, Week 12
Primary	Changes from baseline to post-treatment in composition in level of IL-6.		Baseline, Week 4, Week 8, Week 12
Primary	Changes from baseline to post-treatment in composition in level of IL-8.		Baseline, Week 4, Week 8, Week 12
Primary	Changes from baseline to post-treatment in composition in level of IL-10.		Baseline, Week 4, Week 8, Week 12
Primary	Changes from baseline to post-treatment in composition in level of C-reative protein.		Baseline, Week 4, Week 8, Week 12
Secondary	The linear relationship between gut microbiota and blood glucose and blood lipid level.		Week 4, Week 8, Week 12
Secondary	The linear relationship between gut microbiota and inflammation factors level.		Week 4, Week 8, Week 12