Role of Pioglitazone and Berberine in Treatment of Non-Alcoholic Fatty Liver Disease
Condition: Nonalcoholic Fatty Liver Disease
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

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.
    

Intervention name(s): Life style intervention; pioglitazone; berberine
Intervention type(s): Behavioral; Drug; Drug
Intervention description(s): 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; pioglitazone tablet,15mg qd ,30 minutes before breakfast,for 16 weeks; berberine tablet 0.5g tid,30 minutes before each meal,for 16 weeks
Other intervention name(s): calorie limited diet; aerobic exercise; Actlns; PPAR agonist; Thiazolidinediones; insulin sensitizer; traditional Chinese medicine; herb
Intervention MeSH terms: Pioglitazone; 2,4-thiazolidinedione
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Nonalcoholic Fatty Liver Disease; Pioglitazone; Berberine; Impaired Glucose Metabolism