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

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ClinicalTrials.gov Identifier: NCT03198572
Recruitment Status : Recruiting
First Posted : June 26, 2017
Last Update Posted : March 11, 2019
Sponsor:
Collaborators:
Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
The Affiliated Hospital of Hangzhou Normal University
Tianjin Third Central Hospital
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Xinjiang Medical University
Information provided by (Responsible Party):
Xin Gao, Fudan University

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

Condition or disease Intervention/treatment Phase
Non-alcoholic Steatohepatitis Behavioral: Lifestyle intervention Drug: Placebo Drug: Berberine Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Berberine in Non-alcoholic Steatohepatitis: a Multicentre, Randomised, Placebo-controlled Trial
Actual Study Start Date : August 16, 2017
Estimated Primary Completion Date : December 30, 2020
Estimated Study Completion Date : July 30, 2021


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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Change in anthropometric measures [ Time Frame: 48 weeks ]
    including BMI etc

  5. Change in blood biochemistry [ Time Frame: 48 weeks ]
    including serum aminotransferase levels etc

  6. Change in liver fat content [ Time Frame: 48 weeks ]
    liver fat content determined by 1H MRS (in part of clinical centers)

  7. Change in serum cytokeratin 18 (CK-18) in U/L [ Time Frame: 48 weeks ]
    serum cytokeratin 18 (CK-18) in U/L



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03198572


Contacts
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Contact: Hong-Mei Yan 8613761666976 yan.hongmei@zs-hospital.sh.cn
Contact: Ming-Feng Xia 8613611826871 xia.mingfeng@zs-hospital.sh.cn

Locations
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China, Shanghai
Department of Endocrinology and Metabolism,Shanghai 6th People's Hospital Active, not recruiting
Shanghai, Shanghai, China
China
The Affiliated Hospital of Hangzhou Normal University Recruiting
Hangzhou, China
Contact: Jun-Ping Shi         
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine Active, not recruiting
Shanghai, China
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine Active, not recruiting
Shanghai, China
Tianjin Third Central Hospital Active, not recruiting
Tianjin, China
Xinjiang Medical University Active, not recruiting
Urumqi, China
Sponsors and Collaborators
Fudan University
Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
The Affiliated Hospital of Hangzhou Normal University
Tianjin Third Central Hospital
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Xinjiang Medical University
Investigators
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Principal Investigator: Xin Gao Fudan University

Publications:

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Responsible Party: Xin Gao, Director, Fudan University
ClinicalTrials.gov Identifier: NCT03198572     History of Changes
Other Study ID Numbers: 2016ZSLC04
First Posted: June 26, 2017    Key Record Dates
Last Update Posted: March 11, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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

Keywords provided by Xin Gao, Fudan University:
Non-alcoholic steatohepatitis

Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases