Clinical trial NCT03198572: Efficacy and Safety of Berberine in Non-alcoholic Steatohepatitis
Official title: Efficacy and Safety of Berberine in Non-alcoholic Steatohepatitis: a Multicentre, Randomised, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Non-alcoholic Steatohepatitis
Keywords: Non-alcoholic steatohepatitis
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: Shanghai Jiao Tong University Affiliated Sixth People's Hospital
name: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: The Affiliated Hospital of Hangzhou Normal University
name: Tianjin Third Central Hospital
name: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
name: Xinjiang Medical University
First posted: 2017-06-26
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

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.

Primary outcomes:
measure: Improvement in histologic features of nonalcoholic steatohepatitis by NAFLD activity score (NAS)
timeFrame: 48 weeks
Secondary outcomes:
measure: Improvement in the composites of NAFLD activity scores for steatosis, lobular inflammation, hepatocellular ballooning
timeFrame: 48 weeks
measure: Improvement in liver histological fibrosis staging
timeFrame: 48 weeks
measure: Resolution of NASH
timeFrame: 48 weeks
measure: Change in anthropometric measures
timeFrame: 48 weeks
measure: Change in blood biochemistry
timeFrame: 48 weeks
measure: Change in liver fat content
timeFrame: 48 weeks
measure: Change in serum cytokeratin 18 (CK-18) in U/L
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Endocrinology and Metabolism,Shanghai 6th People's Hospital
state: Shanghai
city: Hangzhou
country: China
facility: The Affiliated Hospital of Hangzhou Normal University
city: Shanghai
country: China
facility: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
city: Shanghai
country: China
facility: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
city: Tianjin
country: China
facility: Tianjin Third Central Hospital
city: Urumqi
country: China
facility: Xinjiang Medical University
Study officials:
affiliation: Fudan University
name: Xin Gao
role: PRINCIPAL_INVESTIGATOR
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