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

This study has been completed.
Sponsor:
Collaborator:
The Geneva Foundation
Information provided by (Responsible Party):
Stephen A Harrison, Brooke Army Medical Center
ClinicalTrials.gov Identifier:
NCT00926016
First received: June 22, 2009
Last updated: February 13, 2012
Last verified: February 2012
  Purpose

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


Condition Intervention
Chronic Hepatitis C
Drug: Pioglitazone (Actos)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Brooke Army Medical Center:

Primary Outcome Measures:
  • 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. [ Time Frame: 104 days ] [ Designated as safety issue: No ]

Enrollment: 23
Study Start Date: June 2006
Study Completion Date: September 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: pioglitazone
Treatment with pioglitazone 45 mg a day for 3 months
Drug: Pioglitazone (Actos)
pioglitazone 45 mg a day
Other Name: Pioglitazone (Actos)
No Intervention: No intervention
Monitoring period without pioglitazone for 3 months

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00926016

Locations
United States, Texas
Brooke Army Medical Center
San Antonio, Texas, United States, 78234
Sponsors and Collaborators
Brooke Army Medical Center
The Geneva Foundation
Investigators
Principal Investigator: Stephen A Harrison, MD Brooke Army Medical Center
  More Information

No publications provided

Responsible Party: Stephen A Harrison, Principal Investigator, Brooke Army Medical Center
ClinicalTrials.gov Identifier: NCT00926016     History of Changes
Other Study ID Numbers: C.2006.152
Study First Received: June 22, 2009
Last Updated: February 13, 2012
Health Authority: United States: Federal Government

Keywords provided by Brooke Army Medical Center:
Hepatitis C

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Pioglitazone
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 22, 2014