The Efficacy and Safety of Pioglitazone in Patients With Nonalcoholic Steatohepatitis

NCT01068444 | Completed Phase 2 DMC

• 1 other identifier: KMUH-HB9608
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

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. 1.Comparison between Pioglitazone and placebo groups in terms of steatosis and liver function tests.
2. 2.Evaluation of clinical safety of Pioglitazone
3. 3.Comparison between Pioglitazone and placebo groups in terms of liver necroinflammation and fibrosis.
4. 4.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).
5. 5.Comparison between Pioglitazone and placebo groups in terms of high-sensitive C-reactive protein changes.

Conditions

Hepatitis

Keywords

NASH; Pioglitazone; Treatment

Outcome Measures

Primary Outcomes (2)

• Comparison between Pioglitazone and placebo groups in terms of steatosis and liver function tests

  9 months

• Evaluation of clinical safety of Pioglitazone

  9 months

Secondary Outcomes (1)

• Comparison between Pioglitazone and placebo groups in terms of liver necroinflammation and fibrosis.

  9 months

Study Arms (2)

Pioglitazone

EXPERIMENTAL

Pioglitazone 30 mg/day for 6 months and 3 months of follow-up period after treatment

Drug: Pioglitazone

Placebo

PLACEBO COMPARATOR

Placebo 30 mg/day for 6 months and 3 months of follow-up period after treatment

Drug: placebo

Interventions

Pioglitazone DRUG

1. Name: GLITOS（Pioglitazone） 2. Dosage form: Tablets 3. Dose(s): 30mg 4. Dosing schedule: QD 5. Duration: 6 months

Also known as: GLITOS

Pioglitazone

placebo DRUG

placebo 30 mg/d for 6 months

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients with 18-70 years of age
• Liver biopsy findings consistent with the diagnosis of NASH with or without compensated cirrhosis within one year before baseline
• Compensated liver disease
• 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
• All fertile males and females must be using two forms of effective contraception during treatment during the 3 months after treatment.
• ALT level between 1.3-5 x ULN for 2 occasions during 6 months before screening.
• HbA1C ≦ 8.0 during screening

You may not qualify if:

• Therapy with any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) \*6 months before baseline.
• 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)
• hepatocellular carcinoma
• History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease
• 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
• History of ischemic heart disease during screening
• New York Heart Association (NYHA) Functional Class 1-4 cardiac status during screening
• Albumin \<3.2g/dL during screening
• 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.
• History of prothrombin time \> 15 seconds or International normalized ratio (INR) \> 1.3
• Organ, stem cell, or bone marrow transplant
• 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
• Active systemic autoimmune disorder
• Pregnancy (or lactation) or, in subjects capable of bearing children, inability / unwillingness to practice adequate contraception
• Females of child-bearing potential (post-puberty) unwilling or unable to have pregnancy testing at any study visit

Sponsors & Collaborators

• Kaohsiung Medical University Chung-Ho Memorial Hospital: lead

Study Sites (2)

Kaohsiung Medical University Hospital

Kaohsiung City, 803, Taiwan

Location

Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University

Kaohsiung City, 812, Taiwan

Location

Related Publications (2)

• Huang JF, Dai CY, Huang CF, Tsai PC, Yeh ML, Hsu PY, Huang SF, Bair MJ, Hou NJ, Huang CI, Liang PC, Lin YH, Wang CW, Hsieh MY, Chen SC, Lin ZY, Yu ML, Chuang WL. First-in-Asian double-blind randomized trial to assess the efficacy and safety of insulin sensitizer in nonalcoholic steatohepatitis patients. Hepatol Int. 2021 Oct;15(5):1136-1147. doi: 10.1007/s12072-021-10242-2. Epub 2021 Aug 12.

  PMID: 34386935 DERIVED

• Huang JF, Yeh ML, Huang CF, Huang CI, Tsai PC, Tai CM, Yang HL, Dai CY, Hsieh MH, Chen SC, Yu ML, Chuang WL. Cytokeratin-18 and uric acid predicts disease severity in Taiwanese nonalcoholic steatohepatitis patients. PLoS One. 2017 May 4;12(5):e0174394. doi: 10.1371/journal.pone.0174394. eCollection 2017.

  PMID: 28472039 DERIVED

MeSH Terms

Conditions

Hepatitis

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Wan-Long Chuang, MD, PhD

  Kaohsiung Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Ph D.

Study Record Dates

• First Submitted: February 11, 2010
• First Posted: February 15, 2010
• Study Start: April 1, 2009
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: July 23, 2020

Record last verified: 2020-07

Locations

TW (2)