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The Efficacy and Safety of Pioglitazone in Patients With Nonalcoholic Steatohepatitis

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Kaohsiung Medical University Chung-Ho Memorial Hospital
Sponsor:
Information provided by (Responsible Party):
Wan-Long Chuang, Kaohsiung Medical University Chung-Ho Memorial Hospital
ClinicalTrials.gov Identifier:
NCT01068444
First received: February 11, 2010
Last updated: October 13, 2013
Last verified: October 2013

February 11, 2010
October 13, 2013
April 2009
March 2014   (final data collection date for primary outcome measure)
  • Comparison between Pioglitazone and placebo groups in terms of steatosis and liver function tests [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
  • Evaluation of clinical safety of Pioglitazone [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01068444 on ClinicalTrials.gov Archive Site
Comparison between Pioglitazone and placebo groups in terms of liver necroinflammation and fibrosis. [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
The Efficacy and Safety of Pioglitazone in Patients With Nonalcoholic Steatohepatitis
A Double-Blind, Randomized, Placebo-Controlled, Phase II Study to Assess the Efficacy and Safety of Pioglitazone in Patients With Nonalcoholic Steatohepatitis

Recent studies have demonstrated that PPARγ as well as diet control could improve glycemic control, decrease serum ALT level, decrease hepatic fat distribution, and increase intrahepatic insulin sensitivity. The purposes of this study are:

1. Primary aims:

  1. Comparison between Pioglitazone and placebo groups in terms of steatosis and liver function tests.
  2. Evaluation of clinical safety of Pioglitazone

2. Secondary aims:

  1. Comparison between Pioglitazone and placebo groups in terms of liver necroinflammation and fibrosis.
  2. The impact of Pioglitazone on the related metabolic index, including insulin resistance(HOMA-IR), newly-onset diabetes, metabolic syndrome, lipid profiles (T-Chol, HDL-C, LDL-C, TG).
  3. Comparison between Pioglitazone and placebo groups in terms of high-sensitive C-reactive protein changes.

3. Interventional aim: Assessment the association between magnetic resonance imaging study and intrahepatic fat distribution before and after Pioglitazone treatment.

Pioglitazone belongs to thiazolidinediones and anti-diabetes drug which decreases the insulin resistance. It increases the use of glucose of peripheral tissues and decrease the production of glucose from liver and dose not influence the production of insulin. It is agonist of peroxisome proliferator-activated receptor-gamma (PPARγ) and by binding to the receptors of PPARγ in various tissues it has effects on transcription of the insulin-dependent gene. In animal model, pioglitazone has shown to influence the metabolism by the insulin-dependent mechanism.

Recent studies have demonstrated that PPARγ as well as diet control could improve glycemic control, decrease serum ALT level, decrease hepatic fat distribution, and increase intrahepatic insulin sensitivity. Meanwhile, PPARγ could also prevent the development of alcohol-induced steatohepatitis, improve hepatic necroinflammatory activity, and decrease lipid deposition. It is not yet clearly known how the effect of P-PARγ agonist among Asian peoples.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Hepatitis
  • Drug: Pioglitazone
    1. Name: GLITOS(Pioglitazone)
    2. Dosage form: Tablets
    3. Dose(s): 30mg
    4. Dosing schedule: QD
    5. Duration: 6 months
    Other Name: GLITOS
  • Drug: placebo
    placebo 30 mg/d for 6 months
  • Experimental: Pioglitazone
    Pioglitazone 30 mg/day for 6 months and 3 months of follow-up period after treatment
    Intervention: Drug: Pioglitazone
  • Placebo Comparator: Placebo
    Placebo 30 mg/day for 6 months and 3 months of follow-up period after treatment
    Intervention: Drug: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
90
July 2014
March 2014   (final data collection date for primary outcome measure)

Main inclusion criteria:

  1. Male and female patients with 18-70 years of age
  2. Liver biopsy findings consistent with the diagnosis of NASH with or without compensated cirrhosis within one year before baseline
  3. Compensated liver disease
  4. Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug
  5. All fertile males and females must be using two forms of effective contraception during treatment during the 3 months after treatment.
  6. ALT level between 1.3-5 x ULN for 2 occasions during 6 months before screening.
  7. HbA1C ≦ 8.0 during screening

Main exclusion criteria:

  1. Therapy with any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) *6 months before baseline.
  2. History or other evidence of a medical condition associated with chronic liver disease other than NASH (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, > 20 g/day for female or > 40 g/day for male, toxin exposures)
  3. hepatocellular carcinoma
  4. History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease
  5. Serum creatinine level >1.5 times the upper limit of normal at screening and calculated creatinine clearance as calculated by Cockcroft and Gault < 60mL/min during screening
  6. History of ischemic heart disease during screening
  7. New York Heart Association (NYHA) Functional Class 1-4 cardiac status during screening
  8. Albumin <3.2g/dL during screening
  9. Total bilirubin >1.2 x ULN during screening. Patients with history of asymptomatic indirect hyperbilirubinemia whose total bilirubin < 2 x ULN and direct bilirubin < 20% of total bilirubin could be included.
  10. History of prothrombin time > 15 seconds or International normalized ratio (INR) > 1.3
  11. Organ, stem cell, or bone marrow transplant
  12. History of serious concurrent medical illness that in the investigator's opinion might interfere with therapy this includes significant systemic illnesses (other than liver disease) such as chronic pancreatitis
  13. Active systemic autoimmune disorder
  14. Pregnancy (or lactation) or, in subjects capable of bearing children, inability / unwillingness to practice adequate contraception
  15. Females of child-bearing potential (post-puberty) unwilling or unable to have pregnancy testing at any study visit
  16. Therapy with a systemic antiviral agent (with the exception of prophylaxis or treatment of influenza or chronic HSV) within the past 30 days prior to screening.
  17. Concurrent participation in another clinical trial in which the subject is or will be exposed to another investigational or a non-investigational drug or device within 6 weeks of the screening visit
  18. Current therapy with insulin within 1 week prior to screening.
  19. Experienced use with PPARg agonist (e.g., rosiglitazone, pioglitazone) within 6 months prior to screening.
  20. Known hypersensitivity to any component of PPARg agonists
  21. A history of hepatotoxicity to TZDs and/or a history of severe edema or a medically serious fluid-related event associated with the use of TZDs
  22. History of metformin use within 3 months prior to screening.
  23. Type Ⅰ diabetes
  24. Seropositive of HBsAg, anti-HCV or anti-HIV during screening or 3 month prior to screening.
Both
18 Years to 70 Years
No
Contact: Wan-Long Chuang, MD, PhD 886 7 3208282 waloch@kmu.edu.tw; research.kmuhb@gmail.com
Taiwan
 
NCT01068444
KMUH-HB9608
Yes
Wan-Long Chuang, Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung Medical University Chung-Ho Memorial Hospital
Not Provided
Principal Investigator: Wan-Long Chuang, MD, PhD Kaohsiung Medical University
Kaohsiung Medical University Chung-Ho Memorial Hospital
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP