Efficacy and Safety of Berberine in Non-alcoholic Steatohepatitis

Non-alcoholic Steatohepatitis Clinical Trial

— EASYBEinNASH  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03198572
• Other study ID #: 2016ZSLC04
• Status: Recruiting
• Phase: Phase 4
• Start date: August 16, 2017
• Est. completion date: July 30, 2024

Study information

• Verified date: August 2023
• Source: Fudan University
• Contact: Hong-Mei Yan
• Phone: 8613761666976
• Email: yan.hongmei[@]zs-hospital.sh.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of berberine treatment on Non-alcoholic Steatohepatitis.

Description:

This is a multicenter, double-blinded, randomized, placebo-controlled clinical trial to investigate the efficacy and safety of berberine on subjects with Non-alcoholic Steatohepatitis.Patients with biopsy-proven non-alcoholic steatohepatitis (NASH) from 18-65 years of age were enrolled. Patients should had no excessive alcohol intake or use of any hepatoprotective or hepatotoxicity medication within 3 months before enrollment.Patients will have an screening period 12 weeks, and a 48-week double-blinded treatment period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: July 30, 2024
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

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

? 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;

? 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.

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Steatohepatitis

Intervention

Behavioral:
• Lifestyle intervention
Lifestyle intervention is consisted of diet control and aerobic exercise. calorie restriction: to subtract 500 kcal from daily calorie intake aerobic exercise: medium intensity aerobic exercise for more than 150 min per week with heart rate around 50-70% of the maximal heart rate.

Drug:
• Placebo
placebo tablets 0.5 tid, 30 minutes before each meal, for 48weeks
• Berberine
Berberine tablets 0.5 tid, 30 minutes before each meal, for 48weeks

Locations

Country	Name	City	State
China	The Affiliated Hospital of Hangzhou Normal University	Hangzhou
China	Department of Endocrinology and Metabolism,Shanghai 6th People's Hospital	Shanghai	Shanghai
China	Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine	Shanghai
China	Xinhua Hospital, Shanghai Jiao Tong University School of Medicine	Shanghai
China	Tianjin Third Central Hospital	Tianjin
China	Xinjiang Medical University	Urumqi

Sponsors (7)

Lead Sponsor	Collaborator
Fudan University	Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, The Affiliated Hospital of Hangzhou Normal University, Tianjin Third Central Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Xinjiang Medical University

Country where clinical trial is conducted

China, 

References & Publications (31)

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* Note: There are 31 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in histologic features of nonalcoholic steatohepatitis by NAFLD activity score (NAS)	A separate system of scoring the histological features of nonalcoholic fatty liver disease (NAFLD) called the NAFLD Activity Score (NAS) was used. An improvement in histologic findings require an improvement by 1 or more points in the hepatocellular ballooning score; no increase in the fibrosis score; and either a decrease in the activity score for nonalcoholic fatty liver disease to a score of 3 or less or a decrease in the activity score of at least 2 points, with at least a 1-point decrease in either the lobular inflammation or steatosis score.	48 weeks
Secondary	Improvement in the composites of NAFLD activity scores for steatosis, lobular inflammation, hepatocellular ballooning	NAFLD activity score (NAS) is composed of steatosis (scale of 0 to 3), lobular inflammation (scale of 0 to 3), hepatocellular ballooning (scale of 0 to 2). Alteration in each component of NAS is measured.	48 weeks
Secondary	Improvement in liver histological fibrosis staging	Fibrosis staging was measured as following criteria: 0=none, 1=perisinusoidal or periportal fibrosis, 2=perisinusoidal and portal/periportal fibrosis, 3=bridging fibrosis, and 4=cirrhosis.the definition of fibrosis stages improvement requires at least one stage.	48 weeks
Secondary	Resolution of NASH	Resolution of NASH was defined as a diagnosis of no steatohepatitis at 48 weeks among those with possible or definite NASH at baseline.	48 weeks
Secondary	Change in anthropometric measures	including BMI etc	48 weeks
Secondary	Change in blood biochemistry	including serum aminotransferase levels etc	48 weeks
Secondary	Change in liver fat content	liver fat content determined by 1H MRS (in part of clinical centers)	48 weeks
Secondary	Change in serum cytokeratin 18 (CK-18) in U/L	serum cytokeratin 18 (CK-18) in U/L	48 weeks