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

Primary Purpose

Type 2 Diabetes

Status
Unknown status
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
1. Berberine hydrochloride tablets ; 2. ProMetS probiotics powder
1. Berberine placebo tablets ; 2. ProMetS probiotics powder
1. Berberine hydrochloride tablets; 2. Probiotics placebo powder
1. Berberine placebo tablets; 2. Probiotics placebo powder
Sponsored by
Shanghai Jiao Tong University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes

Eligibility Criteria

20 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

-

Sites / Locations

  • Ruijin hospital,Shanghai Jiao Tong University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Group A

Group B

Group C

Group D

Arm Description

Outcomes

Primary Outcome Measures

HbA1c

Secondary Outcome Measures

Gut microbiome
Fasting glucose levels
2-hour postprandial glucose levels
Fasting insulin levels
2-hour postprandial insulin levels
Serum Triglycerides
Serum total Cholesterol
Serum HDL-c
Serum LDL-c
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
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.
Inflammation markers (hs-CRP, TNF-alfa, IL-6, and IL-8 etc. in ng/ml)

Full Information

First Posted
August 1, 2016
Last Updated
February 9, 2019
Sponsor
Shanghai Jiao Tong University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT02861261
Brief Title
A Study on the Efficacy and Gut Microbiota of Berberine and Probiotics in Patients With Newly Diagnosed Type 2 Diabetes
Official Title
Probiotics and BeRberine on the Efficacy and Change of Gut MicrObiota in paTients With Newly Diagnosed Type 2 diabEtes（PREMOTE Study）
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Unknown status
Study Start Date
August 18, 2016 (Actual)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
May 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Jiao Tong University School of Medicine

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group A
Arm Type
Experimental
Arm Title
Group B
Arm Type
Experimental
Arm Title
Group C
Arm Type
Experimental
Arm Title
Group D
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
1. Berberine hydrochloride tablets ; 2. ProMetS probiotics powder
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
1. Berberine placebo tablets ; 2. ProMetS probiotics powder
Intervention Description
6 pills of Berberine placebo tablets administered twice a day orally before meal; 4g (2 strips) of ProMetS probiotics powder administered orally every night
Intervention Type
Drug
Intervention Name(s)
1. Berberine hydrochloride tablets; 2. Probiotics placebo powder
Intervention Description
0.6g (6 pills) of Berberine tablets administered twice a day orally before meal; 2 strips of probiotics placebo powder administered orally every night
Intervention Type
Drug
Intervention Name(s)
1. Berberine placebo tablets; 2. Probiotics placebo powder
Intervention Description
6 pills of Berberine placebo tablets administered twice a day orally before meal; 2 strips of probiotics placebo powder administered orally every night
Primary Outcome Measure Information:
Title
HbA1c
Time Frame
13 weeks
Secondary Outcome Measure Information:
Title
Gut microbiome
Time Frame
13 weeks
Title
Fasting glucose levels
Time Frame
13 weeks
Title
2-hour postprandial glucose levels
Time Frame
13 weeks
Title
Fasting insulin levels
Time Frame
13 weeks
Title
2-hour postprandial insulin levels
Time Frame
13 weeks
Title
Serum Triglycerides
Time Frame
13 weeks
Title
Serum total Cholesterol
Time Frame
13 weeks
Title
Serum HDL-c
Time Frame
13 weeks
Title
Serum LDL-c
Time Frame
13 weeks
Title
Blood metabolomics profile measurement
Description
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
Time Frame
13 weeks
Title
Blood Incretin
Description
In aid of multiple ELISA based on xMAP Luminex technology, we will measure gut hormones, including Glp-1, GIP and PYY in ng/ml.
Time Frame
13 weeks
Title
Inflammation markers (hs-CRP, TNF-alfa, IL-6, and IL-8 etc. in ng/ml)
Time Frame
13 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main Inclusion Criteria: Newly diagnosed type 2 diabetes defined as WHO (1999) diagnostic criteria ; Both Genders Eligible; Age: ≥20 and <70 years; BMI: 19.0 ~ 35.0kg/m2; Not receive previously with anti-diabetic agents (oral agents, GLP-1 or insulin); Have at least 2 months of life style intervention to control blood glucose before screening; 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: 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; 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; Allergic to gentamicin or other amino glycosides antibiotics; Histories of acute diabetic complications including diabetic ketoacidosis or hyperosmolar hyperglycemic non-ketotic coma within 3 months; Pregnancy; Acute and chronic diarrhea or severe constipation of the digestive tract diseases; Medical history of malignant tumor (except local skin basal cell carcinoma) in the past 5 years; 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. -
Facility Information:
Facility Name
Ruijin hospital,Shanghai Jiao Tong University School of Medicine
City
Shanghai
State/Province
Shanghai
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
33024120
Citation
Zhang Y, Gu Y, Ren H, Wang S, Zhong H, Zhao X, Ma J, Gu X, Xue Y, Huang S, Yang J, Chen L, Chen G, Qu S, Liang J, Qin L, Huang Q, Peng Y, Li Q, Wang X, Kong P, Hou G, Gao M, Shi Z, Li X, Qiu Y, Zou Y, Yang H, Wang J, Xu G, Lai S, Li J, Ning G, Wang W. Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). Nat Commun. 2020 Oct 6;11(1):5015. doi: 10.1038/s41467-020-18414-8.
Results Reference
derived

Learn more about this trial

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

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