A Study on the Efficacy and Gut Microbiota of Berberine and Probiotics in Patients With Newly Diagnosed Type 2 Diabetes

Phase 3

• Conditions: Type 2 Diabetes
• Interventions: Drug: 1. Berberine hydrochloride tablets ; 2. ProMetS probiotics powder; Drug: 1. Berberine hydrochloride tablets; 2. Probiotics placebo powder; Drug: 1. Berberine placebo tablets ; 2. ProMetS probiotics powder; Drug: 1. Berberine placebo tablets; 2. Probiotics placebo powder

• Registration Number: NCT02861261
• Lead Sponsor: Shanghai Jiao Tong University School of Medicine

Brief Summary

The purpose of this study is to conduct a multicenter randomized, double-blind, placebo-controlled clinical trial, evaluating the effects and change of gut microbiota after berberine and/or probiotics administration in patients with newly diagnosed type 2 diabetes

Detailed Description

In the present study, about 400 newly-diagnosed type 2 diabetes patients will be enrolled from multiple centers in China. Randomisation was computer generated and stratified by age. After screening, eligible subjects will be given Gentamycin Sulfate Sustained-release Tablets 80mg bid po for a week at the washout period, then all participants will be randomly assigned into one of the following four groups: Berberine hydrochloride tablets（0.6g bid po）and ProMetS probiotics powder（4g qN po), Berberine placebo tablets（6 pills bid po) and ProMetS probiotics powder (4g qN po), Berberine hydrochloride tablets（0.6g bid po）and Probiotics placebo powder (2 strips qN po), Berberine placebo tablets（6 pills bid po) and Probiotics placebo powder (2 strips qN po) for 3 months.

The primary objective is to determine whether a combination of probiotics and berberine is preferable to either berberine alone or probiotics alone, in comparison with placebo in improving 1). glycemic control, as measured by change in HbA1c level from baseline to 13-week follow-up, and 2). glycemic control, as measured by change in HbA1c level from baseline to 13-week follow-up in participants aged ≥ 50 years.

Blood, feces and urine samples will be collected before and after treatment. HbA1C, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), GLP-1 , lipids, amino acids, bile acids and other metabolic related components and parameters will be measured. Furthermore, the change of gut microbiota will be evaluated too.

Study Timeline

• Study First Submitted: 2016-08-01
• Study First Submitted QC: 2016-08-05
• Study First Posted: 2016-08-10
• Study Start: 2016-08-18
• Primary Completion: 2017-12
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-09
• Last Update Posted: 2019-02-12
• Study Completion: 2019-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

1. Newly diagnosed type 2 diabetes defined as WHO (1999) diagnostic criteria ; Both Genders Eligible;
2. Age: ≥20 and <70 years;
3. BMI: 19.0 ~ 35.0kg/m2;
4. Not receive previously with anti-diabetic agents (oral agents, GLP-1 or insulin);
5. Have at least 2 months of life style intervention to control blood glucose before screening;
6. HbA1c ≥6.5% and ≤10.0%, and fasting plasma glucose≥7.0 mmol/L and ≤13.3mmol/L at screening.

Details please see the study protocol. -

Main

Exclusion Criteria

1. Significant impaired liver function (defined as alanine transaminase (ALT)> 2.5 times upper limit of normal); Impaired renal function (defined as serum-creatinine> 132μmol/L or eGFR <60 mL/min/1.73m2 ); Mental disease, severe infection, severe anemia, neutropenia disease;
2. Other severe heart disease, such as congenital heart disease, rheumatic heart disease, hypertrophic or dilated cardiomyopathy, defined as New York Heart Association class III or IV;
3. Allergic to gentamicin or other amino glycosides antibiotics;
4. Histories of acute diabetic complications including diabetic ketoacidosis or hyperosmolar hyperglycemic non-ketotic coma within 3 months;
5. Pregnancy;
6. Acute and chronic diarrhea or severe constipation of the digestive tract diseases;
7. Medical history of malignant tumor (except local skin basal cell carcinoma) in the past 5 years;
8. Medical history of intestine, or other digestive tract surgery (such as cholecystectomy) within one year, or other non gastrointestinal surgery within 6 months.

Details please see the study protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A	1. Berberine hydrochloride tablets ; 2. ProMetS probiotics powder	-
Group C	1. Berberine hydrochloride tablets; 2. Probiotics placebo powder	-
Group B	1. Berberine placebo tablets ; 2. ProMetS probiotics powder	-
Group D	1. Berberine placebo tablets; 2. Probiotics placebo powder	-

Primary Outcome Measures

Name	Time	Method
HbA1c	13 weeks

Secondary Outcome Measures

Name	Time	Method
Gut microbiome	13 weeks
Fasting glucose levels	13 weeks
2-hour postprandial glucose levels	13 weeks
Fasting insulin levels	13 weeks
2-hour postprandial insulin levels	13 weeks
Serum Triglycerides	13 weeks
Serum total Cholesterol	13 weeks
Serum HDL-c	13 weeks
Serum LDL-c	13 weeks
Blood metabolomics profile measurement	13 weeks	In aid of LC/MS and GC/MS technique, we will measure the metabolomics molecular profile in blood samples before and after treatment. The metabolomics measurement will help to detect the profile of all kinds of bile acid species, lipids species and amino acid species. The composition change of all these biological molecular induced by the treatment is our major interest rather than single molecular quantification
Blood Incretin	13 weeks	In aid of multiple ELISA based on xMAP Luminex technology, we will measure gut hormones, including Glp-1, GIP and PYY in ng/ml.
Inflammation markers (hs-CRP, TNF-alfa, IL-6, and IL-8 etc. in ng/ml)	13 weeks

Trial Locations

Locations (1)

Ruijin hospital,Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China