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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Berberine Hydrochloride

Intervention / Treatment
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* Drug: Berberine Hydrochloride group
* Drug: Bifidobacterium group
* Drug: Berberine Hydrochloride and Bifidobacterium group
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bifidobacterium, People With Abnormal Glucose Level