Response of Gut Microbiota in Type 2 Diabetes to Hypoglycemic Agents

NCT04287387 | Unknown Phase 4 DMC

• 1 other identifier: APIMCAS2018001
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type2 Diabetes Mellitus

Keywords

type 2 diabetes mellitus; gut microbiota; hypoglycemic drugs

Outcome Measures

Primary Outcomes (10)

• Changes from baseline to post-treatment in composition in gut microbiota analyzed by meta-genome sequencing.

  Baseline, Week 4, Week 8, Week 12

• Changes from baseline to post-treatment in composition in fasting blood glucose.

  Baseline, Week 4, Week 8, Week 12

• Changes from baseline to post-treatment in composition in level of TNF-a.

  Baseline, Week 4, Week 8, Week 12

• Changes from baseline to post-treatment in composition in fasting insulin.

  Baseline, Week 4, Week 8, Week 12

• Changes from baseline to post-treatment in blood lipid including cholesterol, triglycerides, high-density lipoprotein.

  Baseline, Week 4, Week 8, Week 12

• Changes from baseline to post-treatment in composition in 2-hour postprandial blood glucose.

  Baseline, Week 4, Week 8, Week 12

• Changes from baseline to post-treatment in composition in level of IL-6.

  Baseline, Week 4, Week 8, Week 12

• Changes from baseline to post-treatment in composition in level of IL-8.

  Baseline, Week 4, Week 8, Week 12

• Changes from baseline to post-treatment in composition in level of IL-10.

  Baseline, Week 4, Week 8, Week 12

• Changes from baseline to post-treatment in composition in level of C-reative protein.

  Baseline, Week 4, Week 8, Week 12

Secondary Outcomes (2)

• The linear relationship between gut microbiota and blood glucose and blood lipid level.

  Week 4, Week 8, Week 12

• The linear relationship between gut microbiota and inflammation factors level.

  Week 4, Week 8, Week 12

Study Arms (6)

Glucophage group

EXPERIMENTAL

Drug: Glucophage 500Mg Tablet

Acarbose group

EXPERIMENTAL

Drug: Acarbose Tablets

Sitagliptin group

EXPERIMENTAL

Drug: Sitagliptin tablet

Dapagliflozin group

EXPERIMENTAL

Drug: Dapagliflozin Tablet

Pioglitazone group

EXPERIMENTAL

Drug: Pioglitazone Tablets

Glimepiride group

EXPERIMENTAL

Drug: Glimepiride Tablets

Interventions

Glucophage 500Mg Tablet DRUG

0.5g three times daily

Glucophage group

Acarbose Tablets DRUG

50mg three times daily

Acarbose group

Sitagliptin tablet DRUG

100mg once daily

Sitagliptin group

Dapagliflozin Tablet DRUG

10mg once daily

Dapagliflozin group

Pioglitazone Tablets DRUG

30mg once daily

Pioglitazone group

Glimepiride Tablets DRUG

2mg once daily

Glimepiride group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Chinese Academy of Sciences: collaborator

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin; Tablets; Acarbose; Sitagliptin Phosphate; dapagliflozin; Pioglitazone; glimepiride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations; Trisaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Thiazolidinediones; Thiazoles; Sulfur Compounds

Central Study Contacts

Weigang zhao, MD

CONTACT

+86 69151876; xiehezhaoweigang@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2020
• First Posted: February 27, 2020
• Study Start: March 2, 2020
• Primary Completion: March 2, 2021
• Study Completion: March 2, 2021
• Last Updated: February 27, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)