Pioglitazone Before Peginterferon and Ribavirin for Hepatitis C Infection in HIV/HCV-Coinfected Patients With Insulin Resistance

NCT00665353 | Completed Phase 2 Results DMC

• 2 other identifiers: ACTG A52391U01AI068636
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 8

Brief Summary

Insulin resistance is common in people coinfected with HIV and Hepatitis C virus (HCV) and is associated with poor responses to treatment for HCV. Pioglitazone is an FDA-approved medication for the treatment of type 2 diabetes. It works by increasing the body's sensitivity to insulin. The purpose of this study is to determine whether treatment with pioglitazone prior to HCV treatment with peginterferon and ribavirin is safe and effective in improving the treatment outcome in insulin-resistant, HIV/HCV-coinfected people for whom previous treatment with peginterferon and ribavirin was unsuccessful.

Conditions

HIV-1 and Hepatitis C Co-Infection

Keywords

HIV; HCV

Outcome Measures

Primary Outcomes (1)

• The Proportion of All Subjects With HCV Viral Load < 60 IU/mL at Week 24 of Step 2.

  Week 24 of Step 2

Secondary Outcomes (6)

• Safety and Tolerability

  Step 1 (Up to 24 to 28 weeks)

• Safety and Tolerability

  Step 2 (Up to 72 weeks)

• The Proportion of All Subjects With HCV Viral Load < 60 IU/mL at Week 72of Step 2.

  Week 72 of Step 2

• Absolute Change From Entry to Week 24 of Step 1 in AST and ALT.

  From Entry to Week 24 of Step 1

• Absolute Change From Entry to Week 24 of Step 1 in Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR)

  From Entry to Week 24 of Step 1

Study Arms (1)

PIO (step 1) then PIO+PEG-INF+RBV (step 2)

EXPERIMENTAL

All participants in this study will receive pioglitazone therapy for 24 to 28 weeks. Participants will continue pioglitazone and add peginterferon and ribavirin to their treatment regimen for up to 48 additional weeks.

Drug: pioglitazone; Drug: peginterferon; Drug: ribavirin

Interventions

pioglitazone DRUG

Traditionally used in the treatment of type 2 diabetes to increase insulin sensitivity. Participants will take 30 mg daily in tablet form.

PIO (step 1) then PIO+PEG-INF+RBV (step 2)

peginterferon DRUG

Used in the treatment of HCV. Participants will receive 180 mcg subcutaneously once a week.

PIO (step 1) then PIO+PEG-INF+RBV (step 2)

ribavirin DRUG

Used in the treatment of HCV. Participants will receive 1000 to 1200 mg orally per day depending on weight.

PIO (step 1) then PIO+PEG-INF+RBV (step 2)

Eligibility Criteria

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

You may qualify if:

• For Step 1:
• HIV infected
• Exhibited no response to previous treatment with PEG-IFN alfa-2a 180 mcg/week or alfa-2b 1.5 mcg/kg/week and at least 1000 mg/day ribavirin given for at least 12 consecutive weeks. More information on this criterion can be found in the protocol.
• HOMA-IR valued greater than 2.5 within 42 days prior to study entry. More information on this criterion can be found in the protocol.
• CD4 count of at least 200 cells/mm3 within 42 days prior to study entry
• HCV RNA of at least 60 IU/ml by quantitative RT-PCR assay with or without reactive anti-HCV antibodies within 42 days prior to study entry
• Documentation of infection with HCV genotype 1, within 42 days prior to study entry
• On stable or no antiretroviral therapy for 12 weeks prior to study entry. Interruptions in treatment lasting 14 days or less are allowed if the participant reinitiated the same regimen prior to study entry. Dose modifications or changes in drug formulations during the 12 weeks prior to study entry are permissible.
• Participants on antiretroviral therapy should plan to remain on the same therapy for at least 24 weeks after study entry. Participants not on antiretroviral therapy should have no plans to initiate therapy during the first 24 weeks following study entry.
• Participants with documented or suspected hepatic cirrhosis must have a modified Child-Pugh-Turcotte (CPT) within 42 days prior to study entry.
• Participants with documented or suspected hepatic cirrhosis must have either serum alpha-fetoprotein level of 50 ng/ml or less within 24 weeks prior to study entry; OR serum alpha-fetoprotein greater than 50 ng/ml but no greater than 400 ng/ml with an imaging procedure that shows no evidence of a hepatic tumor, both obtained within 24 weeks prior to study entry.
• Certain laboratory values obtained within 42 days prior to study entry. More information on this criterion can be found in the protocol.
• Willing to use effective forms of contraception throughout the study. More information on this criterion can be found in the protocol.
• Ability and willingness of participant to give written informed consent.
• For Step 2:

You may not qualify if:

• Presence of known causes of significant liver disease. More information on this criterion can be found in the protocol.
• Evidence of decompensated liver disease manifested by presence or history of ascites, variceal bleeding, or hepatic encephalopathy
• History of HCV treatment within 28 days prior to study entry
• Evidence that nonresponse to prior HCV treatment may have been due to nonadherence or certain dose reductions. More information on this criterion can be found in the protocol.
• Use of interferon gamma, TNF-alpha inhibitors, rifampin, rifabutin, pyrazinamide, isoniazid, ganciclovir, or hydroxyurea within 14 days prior to study entry
• Current use of didanosine or zidovudine or plans to initiate use of either during the study
• Active drug or alcohol abuse or dependence that, in the opinion of the study investigator, could interfere with adherence to study requirements
• History of uncontrolled seizure disorder
• Uncontrolled depression or other psychiatric disorder, such as untreated Grade 3 psychiatric disorder, Grade 3 disorder not amenable to medical intervention, or any hospitalization within the past 52 weeks that may affect tolerability of study requirements
• History of autoimmune disorders, including but not limited to Crohn's disease, ulcerative colitis, severe psoriasis, and rheumatoid arthritis, that have been exacerbated by previous interferon use
• Any systematic antineoplastic or immunomodulatory treatment or radiation within 24 weeks prior to study entry
• Serious illness including malignancy, active symptomatic coronary artery disease within 24 weeks prior to study entry, or other chronic medical condition that could interfere with safe study completion
• Presence of AIDS-defining opportunistic infections within 12 weeks prior to study entry
• Hemoglobinopathy (e.g., thalassemia major) or any other cause of or tendency to hemolysis. Subjects with thalassemia minor may be enrolled at the discretion of the investigator.
• History of major organ transplantation with an existing functional graft

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (8)

Ucsf Aids Crs (801)

San Francisco, California, 94110, United States

Location

Northwestern University CRS (2701)

Chicago, Illinois, 60611, United States

Location

New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)

Newark, New Jersey, 07103, United States

Location

Cornell CRS (7804)

New York, New York, 10011, United States

Location

NY Univ. HIV/AIDS CRS (401)

New York, New York, 10016, United States

Location

AIDS Care CRS (1108)

Rochester, New York, 14642, United States

Location

Metro Health CRS (2503)

Cleveland, Ohio, 44109, United States

Location

Virginia Commonwealth Univ. Medical Ctr. CRS (31475)

Richmond, Virginia, 23219, United States

Location

Related Publications (4)

• de Larranaga GF, Wingeyer SD, Puga LM, Alonso BS, Benetucci JA. Relationship between hepatitis C virus (HCV) and insulin resistance, endothelial perturbation, and platelet activation in HIV-HCV-coinfected patients under highly active antiretroviral treatment. Eur J Clin Microbiol Infect Dis. 2006 Feb;25(2):98-103. doi: 10.1007/s10096-006-0090-6.

  PMID: 16477441 BACKGROUND

• Patel MR, Mullen MP, Dieterich DT. Sustained virologic response with short-course ribavirin and peginterferon treatment in 2 patients coinfected with HIV and HCV genotype 1. AIDS Read. 2006 Mar;16(3):164, 168-9; discussion 168-9.

  PMID: 16538956 BACKGROUND

• Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmeron J, Diago M, Fernandez-Rodriguez CM, Corpas R, Cruz M, Grande L, Vazquez L, Munoz-De-Rueda P, Lopez-Serrano P, Gila A, Gutierrez ML, Perez C, Ruiz-Extremera A, Suarez E, Castillo J. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology. 2005 Mar;128(3):636-41. doi: 10.1053/j.gastro.2004.12.049.

  PMID: 15765399 BACKGROUND

• Torriani FJ, Rodriguez-Torres M, Rockstroh JK, Lissen E, Gonzalez-Garcia J, Lazzarin A, Carosi G, Sasadeusz J, Katlama C, Montaner J, Sette H Jr, Passe S, De Pamphilis J, Duff F, Schrenk UM, Dieterich DT; APRICOT Study Group. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004 Jul 29;351(5):438-50. doi: 10.1056/NEJMoa040842.

  PMID: 15282351 BACKGROUND

MeSH Terms

Interventions

Pioglitazone; Ribavirin

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

The study did not fully enroll and the small sample size precluded subgroup analysis.

Results Point of Contact

• Title: ACTG ClinicalTrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Marshall Glesby, MD, PhD

  Cornell Clinical Trials Unit, Weill Medical College of Cornell University

  STUDY CHAIR

• Kristen Marks, MD, MS

  New York Presbyterian Hospital-Cornell

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2008
• First Posted: April 23, 2008
• Study Start: March 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: December 1, 2011
• Last Updated: October 12, 2018
• Results First Posted: September 13, 2012

Record last verified: 2018-09

Locations

US (8)