Effectiveness and Safety of Berberine Hydrochloride and Bifidobacterium in People With Abnormal Glucose Level

Effectiveness and Safety of Berberine Hydrochloride and Bifidobacterium in People With Abnormal Glucose Level: an Multicenter, Randomized, Double-blinded, Placebo-controlled Study.

The aim of this study is to assess the beneficial effects of Bifidobacterium and Berberine Hydrochloride on lowering glucose and delaying progress to diabetes in patients with prediabetes and to detect the potential mechanism.

Study Overview

• Status: Completed
• Conditions: Berberine Hydrochloride
• Intervention / Treatment: Drug: placebo; Drug: Berberine Hydrochloride group; Drug: Bifidobacterium group; Drug: Berberine Hydrochloride and Bifidobacterium group

Detailed Description

Gut microbiota may play an important role in patients with prediabetes. Berberine, which is usually used as an antibiotic drug, has been reported a potential glucose-lowering effect in vitro and in vivo studies. Bifidobacterium, as a familiar probiotics, can modulate gut microbiota and improve glucose and lipid metabolism in animal experiments. Therefore, the aim of this study is to assess the beneficial effects of Bifidobacterium and Berberine Hydrochloride on lowering glucose and delaying progress to diabetes in patients with prediabetes and to detect the potential mechanism.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed consent obtained before any trial-related activities.
• Male or female between 18 and 70 years of old.
• 19≤Body mass index(BMI)≤30kg/m^2.
• No participate in any clinical trial at least 3 months.
• Diagnosed impaired fasting glucose(IFG) and impaired glucose tolerance(IGT) or Diabetes.
• In visit 1, 5.60mmol/L≤Fasting plasma glucose(FPG)<8.0mmol/L; in visit 2, 6.1≤FPG<8.0mmol/L or 7.8≤2-hour postprandial plasma glucose(2h-PPG) <17mmol/L.
• Females in child-bearing period should be given birth control.
• No severe disease about heart, lung and kidney.

Exclusion Criteria:

• Type 1 diabetes
• Diabetes patients with previously treated or untreated FPG ≥ 8 mmol/L or 2-h PPG ≥ 17 mmol/L;
• Women of childbearing potential who are pregnant, breastfeeding or intend to become pregnant or are not using adequate contraceptive methods.
• Those who are allergic to study drugs
• Unable to cooperate
• Abnormal liver function, ALT and AST are more than 2 times of the normal upper limit
• Renal injury, blood creatinine ≥133 µmol/L
• Poor blood pressure control, systolic blood pressure SBP≥160mmHg and/or diastolic blood pressure DBP≥95mmHg
• Patients with chronic gastrointestinal diseases (pancreatitis, inflammatory bowel disease) and history of intestinal surgery
• Patients with severe heart disease, such as heart failure, unstable angina pectoris, acute myocardial infarction
• Chronic hypoxic diseases such as emphysema, pulmonary heart disease
• Having obvious diseases of the blood system
• Persons with tumor diseases
• Endocrine diseases, such as hyperthyroidism and hypercortisolism
• Mental illness, abuse of alcohol, drugs or other substances
• Persons with long-term oral or intravenous corticosteroid hormones therapy
• Having stress conditions such as surgery, severe trauma, etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Berberine Hydrochloride group; 2/day, 16 weeks	Drug: Berberine Hydrochloride group
Experimental: Bifidobacterium group; 2/day, 16 weeks	Drug: Bifidobacterium group
Experimental: Berberine Hydrochloride and Bifidobacterium group; 2/day, 16 weeks	Drug: Berberine Hydrochloride and Bifidobacterium group
Placebo Comparator: placebo; bifidobacterium mimetic capsules berberine mimetic tablets,2/day, 16 weeks	Drug: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of absolute value of fasting plasma glucose (mmol/L)	Fasting plasma glucose will be measured during oral glucose tolerance test (OGTT) by glucose oxidase method at baseline and week 16.	baseline and week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of absolute value of 2-hour postprandial plasma glucose (mmol/L)	2-hour postprandial plasma glucose will be measured during OGTT by glucose oxidase method at baseline and week 16.	baseline and week 16
Change of level of HbA1c (%)	HbA1c will be tested in plasma by high-performance liquid chromatography at baseline and week 16.	baseline and week 16
Change of level of systolic pressure (mmHg)	Systolic pressure will be measured by mercurial sphygmomanometer using the standard methods at baseline and week 16.	baseline and week 16
Change of level of diastolic pressure (mmHg)	Diastolic pressure will be measured by mercurial sphygmomanometer using the standard methods at baseline and week 16.	baseline and week 16
Change of level of serum total cholesterol (mmol/L)	Serum total cholesterol will be measured by fully automatic biochemical analyser at baseline and week 16.	baseline and week 16
Change of level of low-density lipoprotein cholesterol (mmol/L)	Serum low-density lipoprotein cholesterol will be measured by fully automatic biochemical analyser at baseline and week 16.	baseline and week 16
Change of level of high-density lipoprotein cholesterol (mmol/L)	Serum high-density lipoprotein cholesterol will be measured by fully automatic biochemical analyser at baseline and week 16.	baseline and week 16
Change of level of triglycerides (mmol/L)	Serum triglycerides will be measured by fully automatic biochemical analyser at baseline and week 16.	baseline and week 16
Change of absolute value of body weight (kg)	Body weight will be measured by weighing scale using the standard methods at baseline and week 16.	baseline and week 16
Change of absolute value of body mass index (BMI) (kg/m^2)	Weight and height will be combined to report BMI in kg/m^2 at baseline and week 16.	baseline and week 16
Change of level of homeostasis model assessment (HOMA) index	Fasting serum insulin and fasting plasma glucose will be calculated for HOMA index at baseline and week 16.	baseline and week 16
Change of level of insulin early-phase secretion index	Fasting serum insulin and 30 min post serum insulin during OGTT will be calculated for early-phase secretion index at baseline and week 16 .	baseline and week 16
Change of level of insulin late-phase secretion index	Fasting serum insulin and 2-hour post serum insulin during OGTT will be calculated for late-phase secretion index at baseline and week 16 .	baseline and week 16
Change of level of GLP-1(pmol/L)	GLP-1 will be measured in serum by ELISA KIT at baseline and week 16.	baseline and week 16
Change of abundances of gut microbiota (%)	Fecal samples will be measured by metagenomic sequencing to obtain abundances of gut microbiota at baseline and week 16.	baseline and week 16

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Collaborators: Xi'an Central Hospital; Second Affiliated Hospital of Xi'an Jiaotong University; Shangluo Central Hospital; Yan'an University Affiliated Hospital; Xi'an Gaoxin Hospital; Shaanxi Aerospace Hospital; Genertec Universal Xi'an Aero-Engine hospital (Xi' an) Co., Ltd; Chang'An Hospital; Yan'an People's Hospital
• Investigators: Principal Investigator: Qiuhe Ph.D. Ji, M.D., Department of Endocrinology,Xi jing Hospital,Fourth Military Medical University

Publications and helpful links

General Publications

• Ming J, Yu X, Xu X, Wang L, Ding C, Wang Z, Xie X, Li S, Yang W, Luo S, He Q, Du Y, Tian Z, Gao X, Ma K, Fang Y, Li C, Zhao J, Wang X, Ji Q. Effectiveness and safety of Bifidobacterium and berberine in human hyperglycemia and their regulatory effect on the gut microbiota: a multi-center, double-blind, randomized, parallel-controlled study. Genome Med. 2021 Aug 9;13(1):125. doi: 10.1186/s13073-021-00942-7.
• Ming J, Xu S, Liu C, Liu X, Jia A, Ji Q. Effectiveness and safety of bifidobacteria and berberine in people with hyperglycemia: study protocol for a randomized controlled trial. Trials. 2018 Jan 26;19(1):72. doi: 10.1186/s13063-018-2438-5.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: October 18, 2017
• First Submitted That Met QC Criteria: October 30, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): March 15, 2021
• Last Update Submitted That Met QC Criteria: March 10, 2021
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Bifidobacterium; People With Abnormal Glucose Level
• Other Study ID Numbers: 2013KTZB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No