Role of Pioglitazone and Berberine in Treatment of Non-Alcoholic Fatty Liver Disease
Information source: Fudan University
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Nonalcoholic Fatty Liver Disease
Intervention: Life style intervention (Behavioral); pioglitazone (Drug); berberine (Drug)
Phase: Phase 2
Sponsored by: Xin Gao
Official(s) and/or principal investigator(s):
Xin GAO, MD, Principal Investigator, Affiliation: Fudan University
The purpose of this study is to evaluate the effects and safety of pioglitazone and
berberine on the basis of lifestyle intervention to non-alcoholic fatty liver disease
patients with impaired glucose regulation or type 2 diabetes mellitus.
Official title: Role of Pioglitazone and Berberine in Treatment of Non-alcoholic Fatty Liver Disease(NAFLD) Patients With Impaired Glucose Regulation or Type 2 Diabetes Mellitus
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Improved metabolic parameters(glucose, lipid, liver enzymes, etc.)
liver fat content
the ratio of withdrawing because of inefficiency
Sedentary lifestyle and poor dietary choices are leading to a weight gain epidemic and
increasing the risk for developing nonalcoholic fatty liver disease (NAFLD). NAFLD is a
group of diseases with too much fat in liver in the absence of excess alcohol consumption.
NAFLD encompasses a histological spectrum ranging from simple hepatic steatosis to
nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. NAFLD is estimated to
affect 25% of the worldwide population and 15. 35% of adults in shanghai urban area.
Epidemiological data showed that the fatty liver may predict, independent of other factors,
the metabolic syndrome, type 2 diabetes, and cardiovascular disease. Therefore, we may
prevent those diseases by treating NAFLD. Life style intervention including activity and
reducing energy intake is recommended by health care providers for optimal health and is the
most common prescribed therapy for individuals diagnosed with NAFLD.
TZDs are oral glucose-lowering medications used to treat type 2 diabetes that enhance
insulin sensitivity. The strong relationship between insulin resistance and NAFLD suggests
that insulin sensitizing therapies such as TZDs might be beneficial in the prevention or
improvement in NAFLD. TZDs bind to the peroxisome proliferator-activated receptors (PPARs),
in part, by facilitating enhanced TG storage by adipocytes, suppressing the ectopic storage
of lipids into liver and skeletal muscle. In addition, TZDs appear to have anti-inflammatory
properties, inhibiting adipocyte gene expression and reducing circulating levels of TNFα
and resistin, and increasing adiponectin concentrations. Some researches demonstrated
that pioglitazone(a TZD) significantly reduced liver fat content of NAFLD, and ameliorated
biological parameters and liver histology of NASH. However, there have not been similar
data of treating chinese NAFLD with pioglitazone.
Berberine (BBR), a compound isolated from a Chinese herb was identified by Weijia  as a
new cholesterol-lowering drug with a mechanism different from that of statin drugs. BBR
elevates LDL receptor(LDLR) expression through a post-transcriptional mechanism that
stabilizes the LDLR-mRNA. Considering the close relationship between NAFLD and lipid
metabolism, we assume that BBR may be effective for NAFLD by improving lipid metabolism.
In order to evaluate these hypotheses, we plan to treat a group of NAFLD patients with
impaired glucose regulation (IGR) or T2DM with pioglitazone or BBR in a randomized, open,
controlled trial for 16 weeks.
Minimum age: 18 Years.
Maximum age: 65 Years.
1. Patients must have an age range between 18 to 65 years (inclusive).
2. Patients with fatty liver confirmed by ultrasound.
3. Patients must meet the criteria for impaired glucose regulation or type 2 diabetes
mellitus (FPG ≥ 5. 6 mmol/L and/or a two hour glucose value ≥ 7. 8 mmol/L).
4. Course of diabetic mellitus no more than 1 years
5. Diabetic patients have not received anti-diabetic drugs, including insulin,
biguanides, sulfonylureas, thiazolidinediones, Alpha-glucosidase inhibitors, or
glinides for 4 weeks before the time of enrollment
6. Patients have not received lipid-regulating drugs (statins, fibrates)for 4 weeks
before the time of enrollment
7. Blood pressure < 160/100 mmHg,after receiving lifestyle therapy and effective
8. Patients must stopped other drugs medications for four weeks prior to entering the
treatment period, such as: silybin, ursodeoxycholic acid, Polyene
Phosphatidylcholine, vitamin E, some herbs with effect of regulating lipid and
protecting liver function, etc.
9. Liver fat content(LFC) assessed by 1H MRS ≥ 13%(LFC was calculated by dividing the
integral of the methylene groups in fatty acid chains of the hepatic triglycerides by
the sum of methylene groups and water).
1. Any causes of chronic liver disease other than NAFLD (such as - but not restricted to
- alcohol or drug abuse, medication, chronic hepatitis B or C, autoimmune, etc.);
2. Patients with significantly impaired liver function: ALT or AST ≥ 2 times upper limit
3. HBsAg (+) and/or HCV-Ab (+);
4. Patients with type 1 diabetes mellitus or gestational diabetes or special type
diabetes, and patients with BMI < 22 Kg/m2;
5. Course of diabetes more than 1 years;
6. Diabetics patients who have taken or are taking oral glucose-lowering drugs or
7. Diabetics patients with a HbA1c > 7. 5% on initial visit;
8. Patients with severe diabetes complications (diabetes ketoacidosis, diabetes coma or
with symptomatic of diabetes coma; dysfunction of nerve, retinopathy, dysfunction of
9. Patients with serum creatinine ≥ 1. 5 mg/dL (133 umol/L);
10. Patients with a history of clinically significant heart disease (myocardial infarct,
heart failure, and or severe cardiac rhythm);
11. Complicating severe infection, within 6 months after operation, severe trauma;
12. Patients with excess alcohol consumption≥140g/week(male); ≥ 70g/week(female);
13. Patients have participated other clinical trials within 24 weeks;
14. Patients with a history of drug allergy to TZDs and berberine;
15. Patients wth gestation or possible gestation or lactation, or males or females who
expecting gestation during clinical trial;
16. Mental diseases patients;
17. Those who refuse to sign informed consent;
18. Any other conditions, which, in the opinion of the investigators would impede
competence or compliance or possibility of hindering completion of the study;
19. Patients with serum triglyceride ≥ 5. 0 mmol/L;
20. Patients with thyroid disease, including hyperthyroidism or hypothyroidism.
Locations and Contacts
Department of Endocrinology and Metabolism,Shanghai Clinical Center of Diabetes,Shanghai Institute of Diabetes,The sixth people's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, Shanghai 200233, China
Department of Endocrinology and Metabolism,The Fifth People's Hospital，Fudan University, Shanghai, Shanghai 200240, China
Endocrinology and Metabolism Department, Zhongshan Hospital, Fudan University,, Shanghai, Shanghai 200032, China
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Starting date: March 2008
Last updated: June 3, 2012