Evaluating berberine for treating Non-alcoholic Steatohepatitis

Efficacy and Safety of Berberine in Non-alcoholic Steatohepatitis: a Multicentre, Randomised, Placebo-controlled Trial

This study is testing if berberine can help improve liver health in people with Non-alcoholic Steatohepatitis (NASH) compared to a placebo.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: methotrexate
• Locations: 6 sites (Shanghai, Shanghai and 5 other locations)
• Trial ID: NCT03198572 on ClinicalTrials.gov

What this trial studies

This multicenter, double-blinded, randomized, placebo-controlled clinical trial aims to assess the efficacy and safety of berberine in patients diagnosed with Non-alcoholic Steatohepatitis (NASH). Participants aged 18 to 75 with biopsy-proven NASH will be enrolled, and they will undergo a 12-week screening period followed by a 48-week treatment phase. The study will compare the effects of berberine against a placebo, alongside lifestyle interventions, to determine its impact on liver health. The diagnosis of NASH will be confirmed through histological evaluation by a panel of pathologists.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with biopsy-confirmed Non-alcoholic Steatohepatitis and a BMI of 40 kg/m2 or less.

Not a fit: Patients with excessive alcohol intake or those on hepatoprotective or hepatotoxic medications within three months prior to enrollment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from Non-alcoholic Steatohepatitis.

How similar studies have performed: Other studies have explored the use of berberine for metabolic conditions, suggesting potential efficacy, but this specific application for NASH is relatively novel.

Eligibility criteria

The inclusion criteria are as follows:

1. 18-75 years old, no limitation for ethnicity and gender.
2. BMI is no more than 40 kg/m2.
3. Patients with NASH based on liver biopsy obtained within 24 weeks before randomization. The histological evidence of NASH is defined as NAS ≥5 \[\] or NAS ≥4 with a minimum score of 1 for all of three components (steatosis, hepatocyte ballooning, and lobular inflammation), the diagnosis of NASH for EASYBEinNASH eligibility is based on reviews by three pathologists. If there are controversial pathologic diagnosis, at least 2 of the 3 pathologists are consistent with the pathologic diagnosis, which will be the final pathological diagnosis. If there are three different pathological diagnoses, it needs to be discussed and make a judgment by the chief pathologist to form the final pathology report.
4. For patients with impaired glucose metabolism, one of the three following conditions needs to be met.

   ① For patients diagnosed as impaired glucose regulation, they will be treated with lifestyle intervention without hypoglycemic drugs;

   ② For patients diagnosed as diabetes and treated with hypoglycemic drugs, the treatment regimen should not be changed and the dosage should remain stable for more than 2 months before randomization;

   ③ For patients diagnosed as diabetes and treated with lifestyle intervention without hypoglycemic drugs, the treatment regimen should not be changed before randomization.
5. All participants agree to sign the informed consent form.

Exclusion criteria

1. Excessive alcohol intake ( \> 140 g per week for men and \>70 g per week for women within 6 months before enrollment);
2. Liver enzymes (ALT or aspartate aminotransferase(AST) is 5 times higher than the upper limit of normal range;
3. Liver diseases caused by other reasons, such as alcohol abuse, viral hepatitis, drugs, auto-immune hepatitis, hereditary liver disease, liver cirrhosis, liver cancer, etc;
4. Biliary tract diseases, biliary obstructive disease, etc;
5. Other diseases that affect glucose and lipid metabolism, such as hypothyroidism, hyperthyroidism, hypercortisolism, etc;
6. Diabetic patients with poor blood glucose control: HbA1c \>9.5%;
7. Use of drugs that may affect the outcome measures of this study 3 months before enrollment, including pioglitazone, GLP-1 receptor agonist, DPP-4 inhibitor, insulin, and glycyrrhizic acid preparation, etc;
8. Chronic kidney disease or severe renal impairment, defined as serum creatinine greater than 2.0mg/dL (176.8umol/L);
9. Life expectancy is no more than 5 years;
10. Pregnant or planning to become pregnant within the next 64 weeks for female participant;
11. Any situation that may affect the implementation or results of the study;
12. Continuous use of drugs that may affect steatohepatitis 3 months before enrollment, such as glucocorticoids, methotrexate, etc;
13. Subjects participated in other clinical trials in the past 4 weeks; The researchers did not think they were suitable for the study.

Where this trial is running

Shanghai, Shanghai and 5 other locations

• Department of Endocrinology and Metabolism,Shanghai 6th People's Hospital — Shanghai, Shanghai, China (Active_not_recruiting)
• The Affiliated Hospital of Hangzhou Normal University — Hangzhou, China (Recruiting)
• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai, China (Active_not_recruiting)
• Xinhua Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai, China (Active_not_recruiting)
• Tianjin Third Central Hospital — Tianjin, China (Active_not_recruiting)
• Xinjiang Medical University — Urumqi, China (Active_not_recruiting)

Study contacts

• Principal investigator: Xin Gao — Fudan University
• Study coordinator: Hong-Mei Yan

Conditions Non-alcoholic Steatohepatitis; Non-alcoholic steatohepatitis