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

Type 2 Diabetes Clinical Trial

Official title:

Probiotics and BeRberine on the Efficacy and Change of Gut MicrObiota in paTients With Newly Diagnosed Type 2 diabEtes（PREMOTE Study）

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02861261
• Other study ID #: CCEMD-20160301
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 18, 2016
• Est. completion date: May 2019

Study information

• Verified date: February 2019
• Source: Shanghai Jiao Tong University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 400
• Est. completion date: May 2019
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 69 Years

Eligibility

Main 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• 1. Berberine hydrochloride tablets ; 2. ProMetS probiotics powder
0.6g (6 pills) of Berberine tablets administered twice a day orally before meal ; 4g (2 strips) of ProMetS probiotics powder administered orally every night
• 1. Berberine placebo tablets ; 2. ProMetS probiotics powder
6 pills of Berberine placebo tablets administered twice a day orally before meal; 4g (2 strips) of ProMetS probiotics powder administered orally every night
• 1. Berberine hydrochloride tablets; 2. Probiotics placebo powder
0.6g (6 pills) of Berberine tablets administered twice a day orally before meal; 2 strips of probiotics placebo powder administered orally every night
• 1. Berberine placebo tablets; 2. Probiotics placebo powder
6 pills of Berberine placebo tablets administered twice a day orally before meal; 2 strips of probiotics placebo powder administered orally every night

Locations

Country	Name	City	State
China	Ruijin hospital,Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Jiao Tong University School of Medicine

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c		13 weeks
Secondary	Gut microbiome		13 weeks
Secondary	Fasting glucose levels		13 weeks
Secondary	2-hour postprandial glucose levels		13 weeks
Secondary	Fasting insulin levels		13 weeks
Secondary	2-hour postprandial insulin levels		13 weeks
Secondary	Serum Triglycerides		13 weeks
Secondary	Serum total Cholesterol		13 weeks
Secondary	Serum HDL-c		13 weeks
Secondary	Serum LDL-c		13 weeks
Secondary	Blood metabolomics profile measurement	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	13 weeks
Secondary	Blood Incretin	In aid of multiple ELISA based on xMAP Luminex technology, we will measure gut hormones, including Glp-1, GIP and PYY in ng/ml.	13 weeks
Secondary	Inflammation markers (hs-CRP, TNF-alfa, IL-6, and IL-8 etc. in ng/ml)		13 weeks