Clinical trial NCT02861261: 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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Type 2 Diabetes
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2016-08-10
Enrollment: 400
Sex: ALL
Minimum age (years): 20
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

-

Primary outcomes:
measure: HbA1c
timeFrame: 13 weeks
Secondary outcomes:
measure: Gut microbiome
timeFrame: 13 weeks
measure: Fasting glucose levels
timeFrame: 13 weeks
measure: 2-hour postprandial glucose levels
timeFrame: 13 weeks
measure: Fasting insulin levels
timeFrame: 13 weeks
measure: 2-hour postprandial insulin levels
timeFrame: 13 weeks
measure: Serum Triglycerides
timeFrame: 13 weeks
measure: Serum total Cholesterol
timeFrame: 13 weeks
measure: Serum HDL-c
timeFrame: 13 weeks
measure: Serum LDL-c
timeFrame: 13 weeks
measure: Blood metabolomics profile measurement
timeFrame: 13 weeks
measure: Blood Incretin
timeFrame: 13 weeks
measure: Inflammation markers (hs-CRP, TNF-alfa, IL-6, and IL-8 etc. in ng/ml)
timeFrame: 13 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin hospital,Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
References:
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.