Clinical trial NCT05647915: Effects of Berberine in Reducing Abdominal Visceral Adipose Tissue Among Individuals with Obesity and NAFLD
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obesity
Obesity, Abdominal
NAFLD
Keywords: berberine hydrochloride
Lead sponsor: China National Center for Cardiovascular Diseases
Sponsor class: OTHER_GOV
First posted: 2022-12-13
Enrollment: 337
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change of visceral fat content
timeFrame: 6 months
measure: Change of liver fat content
timeFrame: 6 months
Secondary outcomes:
measure: Change of fasting plasma glucose
timeFrame: 6 months
measure: Change of HbA1c
timeFrame: 6 months
measure: Change of 2-hour postprandial blood glucose
timeFrame: 6 months
measure: Change of homeostatic model assessment-insulin resistance
timeFrame: 6 months
measure: Change of homeostasis model assessment-β cell
timeFrame: 6 months
measure: Change of homeostasis model assessment-insulin sensitivity
timeFrame: 6 months
measure: Change of serum triglyceride
timeFrame: 6 months
measure: Change of high-density lipoprotein cholesterol
timeFrame: 6 months
measure: Change of low-density lipoprotein cholesterol
timeFrame: 6 months
measure: Change of total cholesterol
timeFrame: 6 months
measure: Change of lipoprotein (a)
timeFrame: 6 months
measure: Change of apolipoprotein
timeFrame: 6 months
measure: Normalization of glucose parameters among participants with prediabetes
timeFrame: 6 months
measure: Change of metabolic syndrome z-score
timeFrame: 6 months
measure: Change of visceral fat index
timeFrame: 6 months
measure: Change of fat liver index
timeFrame: 6 months
measure: Change of triglyceride glucose index
timeFrame: 6 months
measure: Change of serum urine acid
timeFrame: 6 months
measure: Change of serum homocysteine
timeFrame: 6 months
measure: Change of body weight
timeFrame: 6 months
measure: Change of body mass index
timeFrame: 6 months
measure: Change of waist circumference
timeFrame: 6 months
measure: Change of waist-hip ratio
timeFrame: 6 months
measure: Change of waist-height ratio
timeFrame: 6 months
measure: Change of systolic blood pressure
timeFrame: 6 months
measure: Change of diastolic blood pressure
timeFrame: 6 months
Other outcomes:
measure: Change of alanine aminotransferase
timeFrame: 6 months
measure: Change of aspartate aminotransferase
timeFrame: 6 months
measure: Change of γ-GGT
timeFrame: 6 months
measure: Change of fibrosis-4 score
timeFrame: 6 months
measure: Change of NAFLD fibrosis score
timeFrame: 6 months
measure: Change of hypersensitive C-reactive protein
timeFrame: 6 months
measure: Change of interleukin-6
timeFrame: 6 months
measure: Change of tumor necrosis factor-α
timeFrame: 6 months
measure: Change of transforming growth factor-β
timeFrame: 6 months
measure: Change of leptin
timeFrame: 6 months
measure: Change of adiponectin
timeFrame: 6 months
measure: Change of short chain fatty acids
timeFrame: 6 months
measure: Change of trimethylamine
timeFrame: 6 months
measure: Change of trimethylamine oxide
timeFrame: 6 months
measure: Improvement of left ventricular diastolic function (LVDF) among participants with abnormal LVDF at baseline
timeFrame: 6 months
measure: Change of pericardial fat among participants with abnormal LVDF
timeFrame: 6 months
Locations:
city: Beijing
country: China
facility: Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases
Study officials:
affiliation: National Center for Cardiovascular Diseases
name: Jing Li, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Center for Cardiovascular Diseases
name: Haibo Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.