NAFLD, Obesity, Obesity, Abdominal
Conditions
Keywords
berberine hydrochloride
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.
Interventions
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.
BEHAVIORALPlacebo 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.
Sponsors
China National Center for Cardiovascular Diseases
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Data manager and statistician
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of liver fat content | 6 months | Measurement of liver fat content by computed tomography |
| Change of visceral fat content | 6 months | Measurement of visceral fat by computed tomography |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of waist-hip ratio | 6 months | Waist circumference and hip circumference will be combined to report waist-hip ratio. |
| Change of total cholesterol | 6 months | Measurement of total cholesterol |
| Change of lipoprotein (a) | 6 months | Measurement of lipoprotein (a) |
| Change of apolipoprotein | 6 months | Measurement of apolipoprotein |
| Normalization of glucose parameters among participants with prediabetes | 6 months | 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 | 6 months | 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 | 6 months | 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 | 6 months | 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 | 6 months | Triglyceride glucose index (TyG) calculated by TG and FPG. Higher index indicates higher insulin resistance |
| Change of serum urine acid | 6 months | Measurement of serum urine acid |
| Change of serum homocysteine | 6 months | Measurement of serum homocysteine |
| Change of body weight | 6 months | Measurement of body weight in kg |
| Change of body mass index | 6 months | Weight and height will be combined to report BMI in kg/m\^2 |
| Change of waist circumference | 6 months | Measurement of waist circumference in cm |
| Change of waist-height ratio | 6 months | Waist circumference and height will be combined to report waist-height ratio. |
| Change of systolic blood pressure | 6 months | Measurement of systolic blood pressure (SBP) |
| Change of diastolic blood pressure | 6 months | Measurement of diastolic blood pressure (DBP) |
| Change of fasting plasma glucose | 6 months | Measurement of fasting plasma glucose (FPG) |
| Change of HbA1c | 6 months | Measurement of HbA1c |
| Change of 2-hour postprandial blood glucose | 6 months | Measurement of 2-hour postprandial blood glucose (2hPG) |
| Change of homeostatic model assessment-insulin resistance | 6 months | Homeostatic model assessment-insulin resistance (HOMA-IR)= (fasting insulin (mIU/L) \* FPG (mmol/L)) / 22.5 |
| Change of homeostasis model assessment-β cell | 6 months | Homeostatic model assessment (HOMA-β) = (20 x fasting insulin (mIU/L)) / (FPG (mmol/L) - 3.5) |
| Change of homeostasis model assessment-insulin sensitivity | 6 months | Homeostatic model assessment-insulin sensitivity (HOMA-IS)= 1/ HOMA-IR |
| Change of serum triglyceride | 6 months | Measurement of serum triglyceride (TG) |
| Change of high-density lipoprotein cholesterol | 6 months | Measurement of high-density lipoprotein cholesterol |
| Change of low-density lipoprotein cholesterol | 6 months | Measurement of low-density lipoprotein cholesterol |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change of tumor necrosis factor-α | 6 months | Measurement of tumor necrosis factor-α (TNF-α) |
| Change of transforming growth factor-β | 6 months | Measurement of transforming growth factor-β (TGF-β) |
| Change of leptin | 6 months | Measurement of leptin |
| Change of alanine aminotransferase | 6 months | Measurement of alanine aminotransferase (ALT) |
| Change of aspartate aminotransferase | 6 months | Measurement of aspartate aminotransferase (AST) |
| Change of γ-GGT | 6 months | Measurement of γ-GGT |
| Change of fibrosis-4 score | 6 months | Fibrosis-4 score (FIB-4) calculated by age, ALT, AST, platelet count. Higher score indicates higher extent of liver fibrosis. |
| Change of NAFLD fibrosis score | 6 months | 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. |
| Change of hypersensitive C-reactive protein | 6 months | Measurement of hypersensitive C-reactive protein |
| Change of interleukin-6 | 6 months | Measurement of interleukin-6 (IL-6) |
| Change of adiponectin | 6 months | Measurement of adiponectin |
| Improvement of left ventricular diastolic function (LVDF) among participants with abnormal LVDF at baseline | 6 months | Measurement of LVDF by echocardiogram |
| Change of pericardial fat among participants with abnormal LVDF | 6 months | Measurement of pericardial fat by computed tomography |
| Change of trimethylamine oxide | 6 months | Measurement of trimethylamine oxide (TMAO) |
| Change of short chain fatty acids | 6 months | Measurement of short chain fatty acids |
| Change of trimethylamine | 6 months | Measurement of trimethylamine (TMA) |
Countries
China
Outcome results
None listed