Pioglitazone on Viral Kinetics, Cytokines and Innate Immunity in Insulin Resistant CHC GT 1 Subjects

Chronic Hepatitis C Clinical Trial

Official title:

Assessment of the Efficacy of Pioglitazone on Viral Kinetics, Cytokines, and Innate Immunity in a Group of Insulin Resistant, Treatment Naïve, Chronic Hepatitis C, Genotype 1 Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00926016
• Other study ID #: C.2006.152
• Status: Completed
• Phase: N/A
• First received: June 22, 2009
• Last updated: February 13, 2012
• Start date: June 2006
• Est. completion date: September 2010

Study information

• Verified date: February 2012
• Source: Brooke Army Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if rosiglitazone, a medicine used to treat diabetes, improves response to anti-viral treatment.

Description:

The aim of the study will be to determine if an insulin sensitizing thiazolidinedione (TZD) improves (1) baseline viremia, (2) enhances viral kinetics, (3) improves cytokine profiles and (4) up regulates innate cellular immunity (presumably adaptive immunity is up regulated as well) as measured by the bioactivity of the collected biomarkers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: September 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HCV-Ab or HCV-RNA by PCR Positive for at least six months (to rule out acute seroconversion)

• Serum positive for HCV-RNA by PCR assay

• Must have insulin resistance, defined as a QUICKI score < 0.35. QUICKI

• Liver biopsy consistent with CHC within 24 months prior to enrollment

• Compensated liver disease with the following minimum hematological, biochemical, and serologic criteria at the Screening Visit (WNL = within normal limits):

• Hemoglobin values of >12 gm/dL for females and >13 gm/dL for males.

• WBC >3,000/ mm3

• Neutrophil count > 1,500/mm3

• Platelets >65,000/ mm3

• Direct bilirubin, within 20% of ULN

• Indirect bilirubin, within normal limits (WNL)

• Albumin >3gm/dL

• Serum creatinine < 20% above the ULN

• TSH WNL

• Alpha fetoprotein value < 100 ng/mL

Exclusion Criteria:

• Prior interferon based therapy

• Use of insulin

• Fasting glucose levels > 200 mg/dl

• Women who are pregnant or breast-feeding

• No other thiazolidinedione after liver biopsy and/or during the entire study (

• Hepatitis C of non-genotype 1

• Suspected hypersensitivity to pioglitazone

• Any cause for liver disease other than chronic hepatitis C, insulin resistance, or NAFLD, including but not limited to:

• Hemochromatosis

• Alpha-1 antitrypsin deficiency

• Co-infection with HBV

• Wilson's disease

• Autoimmune hepatitis

• Significant alcohol use

• Drug-related liver disease

• Any condition that would prevent the subject from having a liver biopsy.

• Hemoglobinopathies that could potentially compromise patient safety

• Evidence of advanced liver disease such as history or presence of ascites, bleeding varices, spontaneous encephalopathy.

• Participants with organ transplants other than cornea and hair transplant.

• Any known preexisting medical condition that could interfere with the subject's participation in and completion of the protocol such as:

• Preexisting psychiatric condition, especially severe depression, or a history of severe psychiatric disorder, such as major psychoses, suicidal ideation and/or suicidal attempt are excluded

• Substance abuse, such as alcohol, IV drugs and inhaled drugs

• Alcohol consumption is to be strongly discouraged

• Seizure disorders not controlled with medication

• Significant cardiovascular dysfunction within the past 12 months

• Chronic pulmonary disease with documented pulmonary hypertension

• Immunologically mediated disease [e.g., inflammatory bowel disease (Crohn's disease, ulcerative colitis)], rheumatoid arthritis, idiopathic thrombocytopenia purpura, systemic lupus erythematosis, autoimmune hemolytic anemia, scleroderma, severe psoriasis, clinical cryoglobulinemia with vasculitis

• Any medical condition requiring, or likely to require, chronic systemic administration of steroids during the course of the study

• Evidence of an active or suspected cancer or a history of malignancy where the risk of reoccurrence is = 20% within two years

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Pioglitazone (Actos)
pioglitazone 45 mg a day

Locations

Country	Name	City	State
United States	Brooke Army Medical Center	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Brooke Army Medical Center	The Geneva Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in baseline viremia and viral kinetics, and/or pro-inflammatory cytokines decrease, and/or markers of innate immunity are upregulated to position a more favorable response to current CHC therapy.		104 days	No