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

Obesity Clinical Trial

— BRAVO  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05647915
• Other study ID #: 2021-CXGC04-2
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: December 15, 2022
• Est. completion date: December 15, 2023

Study information

• Verified date: December 2022
• Source: China National Center for Cardiovascular Diseases
• Contact: Haibo Zhang, MD
• Phone: +86 60866781
• Email: zhanghaibo[@]fuwai.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 326
• Est. completion date: December 15, 2023
• Est. primary completion date: December 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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, ß -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

Related Conditions & MeSH terms

• NAFLD
• Obesity
• Obesity, Abdominal

Intervention

Drug:
• Berberine plus lifestyle intervention
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.

Behavioral:
• Placebo plus lifestyle intervention
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.

Locations

Country	Name	City	State
China	Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
China National Center for Cardiovascular Diseases

Country where clinical trial is conducted

China, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change of alanine aminotransferase	Measurement of alanine aminotransferase (ALT)	6 months
Other	Change of aspartate aminotransferase	Measurement of aspartate aminotransferase (AST)	6 months
Other	Change of ?-GGT	Measurement of ?-GGT	6 months
Other	Change of fibrosis-4 score	Fibrosis-4 score (FIB-4) calculated by age, ALT, AST, platelet count. Higher score indicates higher extent of liver fibrosis.	6 months
Other	Change of NAFLD fibrosis score	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.	6 months
Other	Change of hypersensitive C-reactive protein	Measurement of hypersensitive C-reactive protein	6 months
Other	Change of interleukin-6	Measurement of interleukin-6 (IL-6)	6 months
Other	Change of tumor necrosis factor-a	Measurement of tumor necrosis factor-a (TNF-a)	6 months
Other	Change of transforming growth factor-ß	Measurement of transforming growth factor-ß (TGF-ß)	6 months
Other	Change of leptin	Measurement of leptin	6 months
Other	Change of adiponectin	Measurement of adiponectin	6 months
Other	Change of short chain fatty acids	Measurement of short chain fatty acids	6 months
Other	Change of trimethylamine	Measurement of trimethylamine (TMA)	6 months
Other	Change of trimethylamine oxide	Measurement of trimethylamine oxide (TMAO)	6 months
Other	Improvement of left ventricular diastolic function (LVDF) among participants with abnormal LVDF at baseline	Measurement of LVDF by echocardiogram	6 months
Other	Change of pericardial fat among participants with abnormal LVDF	Measurement of pericardial fat by computed tomography	6 months
Primary	Change of visceral fat content	Measurement of visceral fat by computed tomography	6 months
Primary	Change of liver fat content	Measurement of liver fat content by computed tomography	6 months
Secondary	Change of fasting plasma glucose	Measurement of fasting plasma glucose (FPG)	6 months
Secondary	Change of HbA1c	Measurement of HbA1c	6 months
Secondary	Change of 2-hour postprandial blood glucose	Measurement of 2-hour postprandial blood glucose (2hPG)	6 months
Secondary	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
Secondary	Change of homeostasis model assessment-ß cell	Homeostatic model assessment (HOMA-ß) = (20 x fasting insulin (mIU/L)) / (FPG (mmol/L) - 3.5)	6 months
Secondary	Change of homeostasis model assessment-insulin sensitivity	Homeostatic model assessment-insulin sensitivity (HOMA-IS)= 1/ HOMA-IR	6 months
Secondary	Change of serum triglyceride	Measurement of serum triglyceride (TG)	6 months
Secondary	Change of high-density lipoprotein cholesterol	Measurement of high-density lipoprotein cholesterol	6 months
Secondary	Change of low-density lipoprotein cholesterol	Measurement of low-density lipoprotein cholesterol	6 months
Secondary	Change of total cholesterol	Measurement of total cholesterol	6 months
Secondary	Change of lipoprotein (a)	Measurement of lipoprotein (a)	6 months
Secondary	Change of apolipoprotein	Measurement of apolipoprotein	6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Change of fat liver index	Fat liver index (FLI) calculated by TG, body mass index, gamma-glutamyltransferase (?-GGT), waist circumference. Higher index indicates higher content of liver fat	6 months
Secondary	Change of triglyceride glucose index	Triglyceride glucose index (TyG) calculated by TG and FPG. Higher index indicates higher insulin resistance	6 months
Secondary	Change of serum urine acid	Measurement of serum urine acid	6 months
Secondary	Change of serum homocysteine	Measurement of serum homocysteine	6 months
Secondary	Change of body weight	Measurement of body weight in kg	6 months
Secondary	Change of body mass index	Weight and height will be combined to report BMI in kg/m^2	6 months
Secondary	Change of waist circumference	Measurement of waist circumference in cm	6 months
Secondary	Change of waist-hip ratio	Waist circumference and hip circumference will be combined to report waist-hip ratio.	6 months
Secondary	Change of waist-height ratio	Waist circumference and height will be combined to report waist-height ratio.	6 months
Secondary	Change of systolic blood pressure	Measurement of systolic blood pressure (SBP)	6 months
Secondary	Change of diastolic blood pressure	Measurement of diastolic blood pressure (DBP)	6 months