Pioglitazone to Treat Fatty Liver in Patients With HIV and Hepatitis C Infections

NCT00742326 | Terminated Phase 4 Results DMC

• 1 other identifier: 080201
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

This study will evaluate the effectiveness of pioglitazone in reducing liver fat content in patients with HIV and hepatitis C virus (HCV) infections. Fatty liver and accompanying insulin resistance in patients with HIV and HCV co-infections is associated with inflammatory changes, liver fibrosis and a poorer response to HCV treatment. Pioglitazone is a drug that helps to reduce the body's resistance to insulin. It is approved by the Food and Drug Administration to treat diabetes. Patients with HIV and HCV co-infections who have hepatic steatosis (fatty liver) may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, magnetic resonance imaging (MRI) of the liver to measure liver fat and, if needed, a liver biopsy to confirm the diagnosis of liver steatosis.

• Participants are randomly assigned to take either pioglitazone therapy or placebo for 48 weeks. This is followed by a second 48-week treatment period in which all participants take pioglitazone.
• There are approximately 12 visits during the 96 weeks of the study. Participants will receive a physical assessment, blood and urine tests at each visit. In addition, periodic assessments of dietary habits, body composition, oral glucose tolerance testing, and health related quality of life questionnaires will be completed.
• A repeat MRI of the liver is performed at 48 weeks and at the end of the study to evaluate any potential changes in liver fat and inflammation. In addition, there is a follow-up liver biopsy at 48 weeks and an optional liver biopsy at 96 weeks.

Conditions

HIV; Hepatitis C; Liver Disease; Fatty Liver; Steatosis

Keywords

HIV; Hepatitis C; Liver Disease; Fatty Liver; Steatosis

Outcome Measures

Primary Outcomes (1)

• Change in Hepatic Steatosis and Hepatic Inflammation/Fibrosis in HIV/HCV Co-infected Patients With Steatosis.

  Change in hepatic steatosis and hepatic inflammation/fibrosis in HIV/HCV co-infected patients with steatosis. Change in Hepatic Fat Content measured by MR spectroscopy: 48 weeks compared to Baseline

  48 weeks

Secondary Outcomes (1)

• Change in Insulin Resistance in HIV- and HCV-infected Patients With Steatosis Compared to Placebo

  48 weeks

Study Arms (2)

Pioglitazone

EXPERIMENTAL

pioglitazone 45 mg daily for 48 weeks

Drug: Pioglitazone

Placebo

PLACEBO COMPARATOR

one capsule daily for 48 weeks

Drug: Placebo

Interventions

Pioglitazone DRUG

45 mg/daily

Also known as: Avandia

Pioglitazone

Placebo DRUG

one capsule daily

Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women, 18 years of age or greater
• Confirmed HIV infection by ELISA and Western blot
• No changes in antiretroviral regimen within the prior 3 months--Individuals not currently taking antiretroviral therapy will be eligible. Individuals requiring medically indicated adjustments of antiretroviral therapy during the course of the study will be eligible.
• Confirmed HCV infection, and no current or recent (within the past 3 months) HCV treatment and no plans to start HCV antiviral therapy in the foreseeable future.
• H-MRS liver fat content greater than 5 percent and confirmed steatosis on liver biopsy within 1 year
• Fasting glucose less than 126 mg/dL
• Platelets greater than or equal to 75,000/uL; INR less than 1.6
• Willingness to avoid medications and herbal supplements which may increase the risk of bleeding for one week prior to and one week following liver biopsy (e.g. aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), Vitamin E, fish oil and gingko biloba).
• Willingness to restrict physical activity 72 hours after liver biopsy
• If premenopausal female, willingness to use 2 forms of effective birth control on this study to avoid pregnancy.
• Have a primary care physician
• Willingness to have specimens stored.

You may not qualify if:

• Current thiazolidinedione use or use in the last 6 months, known allergy or sensitivity to a thiazolidinedione
• Use of insulin or other oral hypoglycemics, or known diabetes
• Current pregnancy, breast feeding, or pregnancy within the past 6 months or desire to become pregnant within the next 2 years.
• Child-Pugh-Turcotte (CPT) score greater than class A
• ALT greater than 4 times the upper limit of normal
• Current or history of heart failure (New York Heart Association \[NYHA\] Class III or IV cardiac status)
• Hemoglobin level less than 9g/dL
• Active or ongoing infection with Hepatitis A or B
• Known or suspected liver disease such as autoimmune hepatitis, Wilson's disease, alpha-1-antitrypsin deficiency, cystic fibrosis, hemochromatosis, glycogen storage disease, amyloidosis, primary biliary cirrhosis, sclerosing cholangitis, or any primary or secondary hepatic tumor
• Current alcohol/substance abuse
• Use of growth hormone, prednisone or other anabolic agents (except for physiologic testosterone replacement) currently or within the past 3 months. One day or less of corticosteroid within the prior 90 days of screening is allowed as is stable dose inhalation corticosteroids
• Concurrent use of ketoconazole
• Active opportunistic infection (except thrush) or neoplasm (except Kaposi's sarcoma, skin cancer, cancer of the cervix or anus)
• Any known contraindications to percutaneous liver biopsy including elevated PT/PTT
• Severe psychiatric illness that would interfere with adherence to protocol requirements

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

VA Medical Center

Washington D.C., District of Columbia, 20422, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Jain MK, Skiest DJ, Cloud JW, Jain CL, Burns D, Berggren RE. Changes in mortality related to human immunodeficiency virus infection: comparative analysis of inpatient deaths in 1995 and in 1999-2000. Clin Infect Dis. 2003 Apr 15;36(8):1030-8. doi: 10.1086/368186. Epub 2003 Apr 2.

  PMID: 12684916 BACKGROUND

• Sulkowski MS, Mast EE, Seeff LB, Thomas DL. Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus. Clin Infect Dis. 2000 Apr;30 Suppl 1:S77-84. doi: 10.1086/313842.

  PMID: 10770916 BACKGROUND

• Sulkowski MS, Mehta SH, Torbenson M, Afdhal NH, Mirel L, Moore RD, Thomas DL. Hepatic steatosis and antiretroviral drug use among adults coinfected with HIV and hepatitis C virus. AIDS. 2005 Mar 24;19(6):585-92. doi: 10.1097/01.aids.0000163935.99401.25.

  PMID: 15802977 BACKGROUND

• Matthews L, Kleiner DE, Chairez C, McManus M, Nettles MJ, Zemanick K, Morse CG, Benator D, Kovacs JA, Hadigan C. Pioglitazone for Hepatic Steatosis in HIV/Hepatitis C Virus Coinfection. AIDS Res Hum Retroviruses. 2015 Oct;31(10):961-6. doi: 10.1089/AID.2015.0093. Epub 2015 Aug 24.

  PMID: 26214341 BACKGROUND

MeSH Terms

Conditions

Hepatitis C; Liver Diseases; Fatty Liver

Interventions

Pioglitazone; Rosiglitazone

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Digestive System Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

The study failed to enroll to the originally established sample size due to slow enrollment.

Results Point of Contact

• Title: Colleen Hadigan MD MPH
• Organization: NIAID

hadiganc@niaid.nih.gov

301-594-5754

Study Officials

• Colleen M Hadigan, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2008
• First Posted: August 27, 2008
• Study Start: August 1, 2008
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: December 9, 2016
• Results First Posted: June 16, 2014

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)