Efficacy and Safety of Berberine in Non-alcoholic Steatohepatitis (EASYBEinNASH)

August 7, 2023 updated by: Xin Gao, Fudan University

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Hangzhou, China
        • Recruiting
        • The Affiliated Hospital of Hangzhou Normal University
        • Contact:
          • Jun-Ping Shi
      • Shanghai, China
        • Active, not 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
      • Tianjin, China
        • Active, not recruiting
        • Tianjin Third Central Hospital
      • Urumqi, China
        • Active, not recruiting
        • Xinjiang Medical University
    • Shanghai
      • Shanghai, Shanghai, China
        • Active, not recruiting
        • Department of Endocrinology and Metabolism,Shanghai 6th People's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Berberine
Berberine was taken orally 0.5g three times per day for 48 weeks, based on lifestyle 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: Berberine
Berberine tablets 0.5 tid, 30 minutes before each meal, for 48weeks
Placebo Comparator: Placebo
Placebo was taken orally 0.5g three times per day for 48 weeks, based on lifestyle 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement in histologic features of nonalcoholic steatohepatitis by NAFLD activity score (NAS)
Time Frame: 48 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement in the composites of NAFLD activity scores for steatosis, lobular inflammation, hepatocellular ballooning
Time Frame: 48 weeks
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
Improvement in liver histological fibrosis staging
Time Frame: 48 weeks
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
Resolution of NASH
Time Frame: 48 weeks
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
Change in anthropometric measures
Time Frame: 48 weeks
including BMI etc
48 weeks
Change in blood biochemistry
Time Frame: 48 weeks
including serum aminotransferase levels etc
48 weeks
Change in liver fat content
Time Frame: 48 weeks
liver fat content determined by 1H MRS (in part of clinical centers)
48 weeks
Change in serum cytokeratin 18 (CK-18) in U/L
Time Frame: 48 weeks
serum cytokeratin 18 (CK-18) in U/L
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Collaborators

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

Investigators

  • Principal Investigator: Xin Gao, Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 16, 2017

Primary Completion (Estimated)

December 30, 2023

Study Completion (Estimated)

July 30, 2024

Study Registration Dates

First Submitted

June 18, 2017

First Submitted That Met QC Criteria

June 22, 2017

First Posted (Actual)

June 26, 2017

Study Record Updates

Last Update Posted (Actual)

August 8, 2023

Last Update Submitted That Met QC Criteria

August 7, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016ZSLC04

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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