Effects of Berberine in Reducing Abdominal Visceral Adipose Tissue Among Individuals With Obesity and NAFLD

Study Overview
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Brief Summary
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This multicenter, double-blinded, randomized controlled trial aims to evaluate the effect of berberine in reducing visceral and liver adipose tissue among individuals with obesity and non-alcoholic fatty liver disease (NAFLD) in China.

Detailed Description
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The trial aims to evaluate the efficacy and safety of berberine treatment for obesity and NAFLD. Potential eligible patients will be recruited from 10-20 medical centers in China. After a 4-week run-in period with berberine, all the eligible participants will be randomized (1:1) to berberine 1.0 g per day plus lifestyle intervention (Arm A) or placebo plus lifestyle intervention (Arm B). The participants will be asked to attend the visit at least once every 2 months, and be followed up for 6 months.

Official Title
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Assess the Effects of Berberine in Reducing Abdominal Visceral Adipose Tissue Among Individuals With Obesity and Non-alcoholic Fatty Liver Disease

Conditions
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Obesity, Obesity, Abdominal, NAFLD

Intervention / Treatment
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* Drug: Berberine plus lifestyle intervention
* Behavioral: Placebo plus lifestyle intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants aged ≥18 years Participants with obesity (i.e., BMI ≥ 28 kg/m2) and abdominal obesity (i.e., waist circumference ≥85 cm in female or waist circumference ≥90 cm in male) Participants with NAFLD diagnosed by ultrasound, computed tomography or magnetic resonance imaging Exclusion Criteria: Patients with established coronary heart disease, stroke, or peripheral arterial disease Patients diagnosed with diabetes or taking oral glucose-lowering drugs Patients with severely uncontrolled hypertension (i.e., SBP≥180mmHg and/or DBP ≥110mmHg) Excess alcohol consumption (i.e., alcohol ≥ 20 g/day in female or alcohol ≥ 30 g/day in male) Other causes of fatty liver disease, including alcohol or drug abuse, hepatitis B or C, autoimmune, hepatolenticular degeneration, total parenteral nutrition, inflammatory bowel disease, celiac disease, hypothyroidism, Cushing syndrome, β -lipoprotein deficiency, lipid atrophy diabetes, Mauriac syndrome, etc. Patients with thyroid disease, including hyperthyroidism or hypothyroidism Patients with cardiac insufficiency ALT or AST ≥ 3 times upper limit of normal, liver cirrhosis or hepatic insufficiency Patients with renal insufficiency: estimated glomerular filtration rate (eGFR) < 60 ml/(min×1.73m2) Patients who had weight loss surgery, or are currently taking drugs for weight loss, or plan to have weight loss surgery or drugs in the following 6 months Patients diagnosed with glucose-6-phosphate dehydrogenase (G6PD) deficiency Taking berberine or drug containing berberine in the past 1 month Any adverse reaction to berberine Severe constipation, diarrhea, and/or severe chronic intestinal diseases (e.g., ulcerative colitis, Crohn's disease, irritable bowel syndrome, etc.) Patients who had to use long-term or intermittent corticosteroids, immunosuppressants, antibiotics, or other drugs that affect inflammatory biomarkers Women who are pregnant or breastfeeding, or those who plan to be pregnant during the trial Patients with malignant tumors Patients with mental disorders, cognitive disorders, and/or other serious diseases Those who participated or have been participating other trials during the last 3 months Any other conditions that may hinder the compliance to the study intervention or follow-up visit

Ages Eligible for Study
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Minimum Age: 18 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 group<br>Berberine hydrochloride plus lifestyle intervention | Drug: Berberine plus lifestyle intervention<br>* berberine hydrochloride 500mg twice a day for 6 months plus lifestyle intervention. Lifestyle intervention is based on Guidelines of prevention and treatment for non-alcoholic fatty liver disease (2018 update) and China Blue Paper on Obesity Prevention and Control, including health education on diet, physical activity and weight loss, etc.<br>|
| Placebo Comparator: placebo group<br>Placebo plus lifestyle intervention | Behavioral: Placebo plus lifestyle intervention<br>* Placebo with identical shape, colour, odour and taste twice a day plus lifestyle intervention. Lifestyle intervention is based on Guidelines of prevention and treatment for non-alcoholic fatty liver disease (2018 update) and China Blue Paper on Obesity Prevention and Control, including health education on diet, physical activity and weight loss, etc.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of visceral fat content | Measurement of visceral fat by computed tomography | 6 months | 
| Change of liver fat content | Measurement of liver fat content by computed tomography | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of fasting plasma glucose | Measurement of fasting plasma glucose (FPG) | 6 months | 
| Change of HbA1c | Measurement of HbA1c | 6 months | 
| Change of 2-hour postprandial blood glucose | Measurement of 2-hour postprandial blood glucose (2hPG) | 6 months | 
| Change of homeostatic model assessment-insulin resistance | Homeostatic model assessment-insulin resistance (HOMA-IR)= (fasting insulin (mIU/L) * FPG (mmol/L)) / 22.5 | 6 months | 
| Change of homeostasis model assessment-β cell | Homeostatic model assessment (HOMA-β) = (20 x fasting insulin (mIU/L)) / (FPG (mmol/L) - 3.5) | 6 months | 
| Change of homeostasis model assessment-insulin sensitivity | Homeostatic model assessment-insulin sensitivity (HOMA-IS)= 1/ HOMA-IR | 6 months | 
| Change of serum triglyceride | Measurement of serum triglyceride (TG) | 6 months | 
| Change of high-density lipoprotein cholesterol | Measurement of high-density lipoprotein cholesterol | 6 months | 
| Change of low-density lipoprotein cholesterol | Measurement of low-density lipoprotein cholesterol | 6 months | 
| Change of total cholesterol | Measurement of total cholesterol | 6 months | 
| Change of lipoprotein (a) | Measurement of lipoprotein (a) | 6 months | 
| Change of apolipoprotein | Measurement of apolipoprotein | 6 months | 
| Normalization of glucose parameters among participants with prediabetes | Meeting all three criteria: 1) FPG<6.1 mmol/L; 2) 2hPG<7.8 mmol/L; 3) HbA1c<5.7% | 6 months | 
| Change of metabolic syndrome z-score | Metabolic syndrome z-score calculated by the five components, including waist circumference, HDL-C, blood pressure, TG and FPG. Higher score indicates greater severity of metabolic syndrome | 6 months | 
| Change of visceral fat index | Visceral fat index calculated by waist circumference, body mass index, TG, HDL-C. Higher index indicates higher content of visceral fat | 6 months | 
| Change of fat liver index | Fat liver index (FLI) calculated by TG, body mass index, gamma-glutamyltransferase (γ-GGT), waist circumference. Higher index indicates higher content of liver fat | 6 months | 
| Change of triglyceride glucose index | Triglyceride glucose index (TyG) calculated by TG and FPG. Higher index indicates higher insulin resistance | 6 months | 
| Change of serum urine acid | Measurement of serum urine acid | 6 months | 
| Change of serum homocysteine | Measurement of serum homocysteine | 6 months | 
| Change of body weight | Measurement of body weight in kg | 6 months | 
| Change of body mass index | Weight and height will be combined to report BMI in kg/m^2 | 6 months | 
| Change of waist circumference | Measurement of waist circumference in cm | 6 months | 
| Change of waist-hip ratio | Waist circumference and hip circumference will be combined to report waist-hip ratio. | 6 months | 
| Change of waist-height ratio | Waist circumference and height will be combined to report waist-height ratio. | 6 months | 
| Change of systolic blood pressure | Measurement of systolic blood pressure (SBP) | 6 months | 
| Change of diastolic blood pressure | Measurement of diastolic blood pressure (DBP) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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berberine hydrochloride