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

Primary Purpose

Obesity, Obesity, Abdominal, NAFLD

Status
Not yet recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Berberine plus lifestyle intervention
Placebo plus lifestyle intervention
Sponsored by
China National Center for Cardiovascular Diseases
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obesity focused on measuring berberine hydrochloride

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

berberine group

placebo group

Arm Description

Berberine hydrochloride plus lifestyle intervention

Placebo plus lifestyle intervention

Outcomes

Primary Outcome Measures

Change of visceral fat content
Measurement of visceral fat by computed tomography
Change of liver fat content
Measurement of liver fat content by computed tomography

Secondary Outcome Measures

Change of fasting plasma glucose
Measurement of fasting plasma glucose (FPG)
Change of HbA1c
Measurement of HbA1c
Change of 2-hour postprandial blood glucose
Measurement of 2-hour postprandial blood glucose (2hPG)
Change of homeostatic model assessment-insulin resistance
Homeostatic model assessment-insulin resistance (HOMA-IR)= (fasting insulin (mIU/L) * FPG (mmol/L)) / 22.5
Change of homeostasis model assessment-β cell
Homeostatic model assessment (HOMA-β) = (20 x fasting insulin (mIU/L)) / (FPG (mmol/L) - 3.5)
Change of homeostasis model assessment-insulin sensitivity
Homeostatic model assessment-insulin sensitivity (HOMA-IS)= 1/ HOMA-IR
Change of serum triglyceride
Measurement of serum triglyceride (TG)
Change of high-density lipoprotein cholesterol
Measurement of high-density lipoprotein cholesterol
Change of low-density lipoprotein cholesterol
Measurement of low-density lipoprotein cholesterol
Change of total cholesterol
Measurement of total cholesterol
Change of lipoprotein (a)
Measurement of lipoprotein (a)
Change of apolipoprotein
Measurement of apolipoprotein
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%
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
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
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
Change of triglyceride glucose index
Triglyceride glucose index (TyG) calculated by TG and FPG. Higher index indicates higher insulin resistance
Change of serum urine acid
Measurement of serum urine acid
Change of serum homocysteine
Measurement of serum homocysteine
Change of body weight
Measurement of body weight in kg
Change of body mass index
Weight and height will be combined to report BMI in kg/m^2
Change of waist circumference
Measurement of waist circumference in cm
Change of waist-hip ratio
Waist circumference and hip circumference will be combined to report waist-hip ratio.
Change of waist-height ratio
Waist circumference and height will be combined to report waist-height ratio.
Change of systolic blood pressure
Measurement of systolic blood pressure (SBP)
Change of diastolic blood pressure
Measurement of diastolic blood pressure (DBP)

Full Information

First Posted
November 16, 2022
Last Updated
December 4, 2022
Sponsor
China National Center for Cardiovascular Diseases
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1. Study Identification

Unique Protocol Identification Number
NCT05647915
Brief Title
Effects of Berberine in Reducing Abdominal Visceral Adipose Tissue Among Individuals With Obesity and NAFLD
Acronym
BRAVO
Official Title
Assess the Effects of Berberine in Reducing Abdominal Visceral Adipose Tissue Among Individuals With Obesity and Non-alcoholic Fatty Liver Disease
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 15, 2022 (Anticipated)
Primary Completion Date
December 15, 2023 (Anticipated)
Study Completion Date
December 15, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
China National Center for Cardiovascular Diseases

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Obesity, Abdominal, NAFLD
Keywords
berberine hydrochloride

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
326 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
berberine group
Arm Type
Experimental
Arm Description
Berberine hydrochloride plus lifestyle intervention
Arm Title
placebo group
Arm Type
Placebo Comparator
Arm Description
Placebo plus lifestyle intervention
Intervention Type
Drug
Intervention Name(s)
Berberine plus lifestyle intervention
Intervention Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Placebo plus lifestyle intervention
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change of visceral fat content
Description
Measurement of visceral fat by computed tomography
Time Frame
6 months
Title
Change of liver fat content
Description
Measurement of liver fat content by computed tomography
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Change of fasting plasma glucose
Description
Measurement of fasting plasma glucose (FPG)
Time Frame
6 months
Title
Change of HbA1c
Description
Measurement of HbA1c
Time Frame
6 months
Title
Change of 2-hour postprandial blood glucose
Description
Measurement of 2-hour postprandial blood glucose (2hPG)
Time Frame
6 months
Title
Change of homeostatic model assessment-insulin resistance
Description
Homeostatic model assessment-insulin resistance (HOMA-IR)= (fasting insulin (mIU/L) * FPG (mmol/L)) / 22.5
Time Frame
6 months
Title
Change of homeostasis model assessment-β cell
Description
Homeostatic model assessment (HOMA-β) = (20 x fasting insulin (mIU/L)) / (FPG (mmol/L) - 3.5)
Time Frame
6 months
Title
Change of homeostasis model assessment-insulin sensitivity
Description
Homeostatic model assessment-insulin sensitivity (HOMA-IS)= 1/ HOMA-IR
Time Frame
6 months
Title
Change of serum triglyceride
Description
Measurement of serum triglyceride (TG)
Time Frame
6 months
Title
Change of high-density lipoprotein cholesterol
Description
Measurement of high-density lipoprotein cholesterol
Time Frame
6 months
Title
Change of low-density lipoprotein cholesterol
Description
Measurement of low-density lipoprotein cholesterol
Time Frame
6 months
Title
Change of total cholesterol
Description
Measurement of total cholesterol
Time Frame
6 months
Title
Change of lipoprotein (a)
Description
Measurement of lipoprotein (a)
Time Frame
6 months
Title
Change of apolipoprotein
Description
Measurement of apolipoprotein
Time Frame
6 months
Title
Normalization of glucose parameters among participants with prediabetes
Description
Meeting all three criteria: 1) FPG<6.1 mmol/L; 2) 2hPG<7.8 mmol/L; 3) HbA1c<5.7%
Time Frame
6 months
Title
Change of metabolic syndrome z-score
Description
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
Time Frame
6 months
Title
Change of visceral fat index
Description
Visceral fat index calculated by waist circumference, body mass index, TG, HDL-C. Higher index indicates higher content of visceral fat
Time Frame
6 months
Title
Change of fat liver index
Description
Fat liver index (FLI) calculated by TG, body mass index, gamma-glutamyltransferase (γ-GGT), waist circumference. Higher index indicates higher content of liver fat
Time Frame
6 months
Title
Change of triglyceride glucose index
Description
Triglyceride glucose index (TyG) calculated by TG and FPG. Higher index indicates higher insulin resistance
Time Frame
6 months
Title
Change of serum urine acid
Description
Measurement of serum urine acid
Time Frame
6 months
Title
Change of serum homocysteine
Description
Measurement of serum homocysteine
Time Frame
6 months
Title
Change of body weight
Description
Measurement of body weight in kg
Time Frame
6 months
Title
Change of body mass index
Description
Weight and height will be combined to report BMI in kg/m^2
Time Frame
6 months
Title
Change of waist circumference
Description
Measurement of waist circumference in cm
Time Frame
6 months
Title
Change of waist-hip ratio
Description
Waist circumference and hip circumference will be combined to report waist-hip ratio.
Time Frame
6 months
Title
Change of waist-height ratio
Description
Waist circumference and height will be combined to report waist-height ratio.
Time Frame
6 months
Title
Change of systolic blood pressure
Description
Measurement of systolic blood pressure (SBP)
Time Frame
6 months
Title
Change of diastolic blood pressure
Description
Measurement of diastolic blood pressure (DBP)
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Change of alanine aminotransferase
Description
Measurement of alanine aminotransferase (ALT)
Time Frame
6 months
Title
Change of aspartate aminotransferase
Description
Measurement of aspartate aminotransferase (AST)
Time Frame
6 months
Title
Change of γ-GGT
Description
Measurement of γ-GGT
Time Frame
6 months
Title
Change of fibrosis-4 score
Description
Fibrosis-4 score (FIB-4) calculated by age, ALT, AST, platelet count. Higher score indicates higher extent of liver fibrosis.
Time Frame
6 months
Title
Change of NAFLD fibrosis score
Description
NAFLD fibrosis score (NFS) calculated by age, BMI, status of dysglycemia, ALT, AST, platelet count, serum albumin concentration. Higher score indicates higher extent of liver fibrosis.
Time Frame
6 months
Title
Change of hypersensitive C-reactive protein
Description
Measurement of hypersensitive C-reactive protein
Time Frame
6 months
Title
Change of interleukin-6
Description
Measurement of interleukin-6 (IL-6)
Time Frame
6 months
Title
Change of tumor necrosis factor-α
Description
Measurement of tumor necrosis factor-α (TNF-α)
Time Frame
6 months
Title
Change of transforming growth factor-β
Description
Measurement of transforming growth factor-β (TGF-β)
Time Frame
6 months
Title
Change of leptin
Description
Measurement of leptin
Time Frame
6 months
Title
Change of adiponectin
Description
Measurement of adiponectin
Time Frame
6 months
Title
Change of short chain fatty acids
Description
Measurement of short chain fatty acids
Time Frame
6 months
Title
Change of trimethylamine
Description
Measurement of trimethylamine (TMA)
Time Frame
6 months
Title
Change of trimethylamine oxide
Description
Measurement of trimethylamine oxide (TMAO)
Time Frame
6 months
Title
Improvement of left ventricular diastolic function (LVDF) among participants with abnormal LVDF at baseline
Description
Measurement of LVDF by echocardiogram
Time Frame
6 months
Title
Change of pericardial fat among participants with abnormal LVDF
Description
Measurement of pericardial fat by computed tomography
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Haibo Zhang, MD
Phone
+86 60866781
Email
zhanghaibo@fuwai.org
First Name & Middle Initial & Last Name or Official Title & Degree
Bin Wang, PhD
Phone
+86 60866718
Email
wangbin@fuwai.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jing Li, PhD
Organizational Affiliation
National Center for Cardiovascular Diseases
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Haibo Zhang, MD
Organizational Affiliation
National Center for Cardiovascular Diseases
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases
City
Beijing
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Haibo Zhang, MD
Phone
+86 60866781
Email
zhanghaibo@fuwai.org

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
26252777
Citation
Yan HM, Xia MF, Wang Y, Chang XX, Yao XZ, Rao SX, Zeng MS, Tu YF, Feng R, Jia WP, Liu J, Deng W, Jiang JD, Gao X. Efficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease. PLoS One. 2015 Aug 7;10(8):e0134172. doi: 10.1371/journal.pone.0134172. eCollection 2015.
Results Reference
background
PubMed Identifier
34535644
Citation
Harrison SA, Gunn N, Neff GW, Kohli A, Liu L, Flyer A, Goldkind L, Di Bisceglie AM. A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes. Nat Commun. 2021 Sep 17;12(1):5503. doi: 10.1038/s41467-021-25701-5.
Results Reference
background

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

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