Role of Pioglitazone and Berberine in Treatment of Non-Alcoholic Fatty Liver Disease

June 3, 2012 updated by: Xin Gao

Role of Pioglitazone and Berberine in Treatment of Non-alcoholic Fatty Liver Disease(NAFLD) Patients With Impaired Glucose Regulation or Type 2 Diabetes Mellitus

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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[1] and 15.35% of adults in shanghai urban area[2]. 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[3] and resistin[4], and increasing adiponectin concentrations[5]. Some researches demonstrated that pioglitazone(a TZD) significantly reduced liver fat content of NAFLD, and ameliorated biological parameters and liver histology of NASH[6]. 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 [7] 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.

Study Type

Interventional

Enrollment (Actual)

184

Phase

  • Phase 2

Contacts and Locations

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

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Endocrinology and Metabolism Department, Zhongshan Hospital, Fudan University,
      • Shanghai, Shanghai, China, 200233
        • 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, China, 200240
        • Department of Endocrinology and Metabolism,The Fifth People's Hospital，Fudan University

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 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  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 anti-hypertensive drugs.
  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).

Exclusion Criteria:

  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 of normal;
  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 insulin;
  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 kidney）;
  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.

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lifestyle intervention
Life style intervention including aerobic exercise and reducing energy intake(-500kcal) without drug
Behavioral: Life style intervention

calorie limited diet: to subtract 500 kcal from daily mean calorie intake when entering the treatment

activity: medium intensity aerobic exercise for more than 150 min per week with heart rate around 50-70% of the maximal heart rate; or higher-intensity aerobic exercise for more than 90min per week with heart rate around 70% of the maximal heart rate

Other Names:
  • aerobic exercise
  • calorie limited diet
Experimental: Life style intervention, pioglitazone
Life style intervention with pioglitazone 15mg qd for 16 weeks
Behavioral: Life style intervention

calorie limited diet: to subtract 500 kcal from daily mean calorie intake when entering the treatment

activity: medium intensity aerobic exercise for more than 150 min per week with heart rate around 50-70% of the maximal heart rate; or higher-intensity aerobic exercise for more than 90min per week with heart rate around 70% of the maximal heart rate

Other Names:
  • aerobic exercise
  • calorie limited diet
Drug: pioglitazone
pioglitazone tablet,15mg qd ,30 minutes before breakfast,for 16 weeks
Other Names:
  • Actlns
  • PPAR agonist
  • Thiazolidinediones
  • insulin sensitizer
Experimental: Life style intervention, berberine
Life style intervention with berberine 0.5g tid for 16 weeks
Behavioral: Life style intervention

calorie limited diet: to subtract 500 kcal from daily mean calorie intake when entering the treatment

activity: medium intensity aerobic exercise for more than 150 min per week with heart rate around 50-70% of the maximal heart rate; or higher-intensity aerobic exercise for more than 90min per week with heart rate around 70% of the maximal heart rate

Other Names:
  • aerobic exercise
  • calorie limited diet
Drug: berberine
berberine tablet 0.5g tid,30 minutes before each meal,for 16 weeks
Other Names:
  • traditional Chinese medicine
  • herb

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improved metabolic parameters(glucose, lipid, liver enzymes, etc.)
Time Frame: 16 weeks
improvement of the metabolic parameters, including serum glucose of OGTT, fasting glucose,2 hour glucose,area under the glucose curve and HbA1c,lipid profile（TC、TG、HDL-c、LDL-c、ApoA、ApoB、ApoE and Lpa），liver enzymes（ALT,AST,ALP,γ-GT）.
16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
liver fat content
Time Frame: 16 weeks
improvement of liver fat content by 1H NMR spectroscopy
16 weeks
serum insulin
Time Frame: 16 weeks
improvement of serum insulin including fasting insulin,2 hour insulin and area under insulin curve.
16 weeks
the ratio of withdrawing because of inefficiency
Time Frame: 16 weeks
16 weeks

Collaborators and Investigators

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

Sponsor

Xin Gao

Collaborators

Shanghai Jiao Tong University School of Medicine
Shanghai Municipal Science and Technology Commission

Investigators

  • Principal Investigator: Xin GAO, MD, 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

March 1, 2008

Primary Completion (Actual)

August 1, 2011

Study Completion (Actual)

August 1, 2011

Study Registration Dates

First Submitted

March 3, 2008

First Submitted That Met QC Criteria

March 10, 2008

First Posted (Estimate)

March 12, 2008

Study Record Updates

Last Update Posted (Estimate)

June 5, 2012

Last Update Submitted That Met QC Criteria

June 3, 2012

Last Verified

June 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07JC14011

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.

Clinical Trials on Nonalcoholic Fatty Liver Disease

Clinical Trials on Life style intervention

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mauritius

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe