HIV InfectionsPhase 2NCT00441272
Pioglitazone to Treat Fatty Liver in People With HIV Infection
A Phase 2 study testing Pioglitazone in people with HIV Infections and Hepatic Steatosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will determine whether pioglitazone (Actos, a drug approved to treat diabetes, can benefit HIV-infected people with fatty liver. Fatty changes of the liver (also known as steatosis) have been linked to diabetes and long-term liver damage in some patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections, Hepatic Steatosis, Insulin Resistance
- What is being tested?
- Pioglitazone
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2007to Oct 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Liver-to-spleen attenuation ratio less than 1 determined by CT and hepatic steatosis on liver biopsy within the past 1 year scored grade 1 or greater (i.e. greater than or equal to 5 percent of hepatocytes).
- Fasting glucose less than 126 mg/dL.
- Platelets greater than 50,000/microliters.
Show all 10Show fewer
- Willingness to avoid medications and herbal supplements that may increase the risk of bleeding for one week prior to and one week following liver biopsy (e.g. aspirin, NSAIDs and ginko biloba).
- Willingness to restrict physical activity 72 hours after liver biopsy.
- Willingness to use 2 effective forms of contraception during the study to avoid pregnancy.
- Have a primary care physician.
Who cannot join
- 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.
- MELD score greater than 9 or previously diagnosed cirrhosis.
- ALT greater than 3 times the upper limit of normal.
- Current or history of heart failure (NYHA Class III or IV cardiac status).
Show all 18Show fewer
- Hemoglobin level less than 9g/dL.
- Active or ongoing infection with Hepatitis A, B, or C.
- Known or suspected liver disease such as autoimmune hepatitis, Wilson's disease, alpha-1-antitrypsin deficiency, cystic fibrosis, hemachromatosis, glycogen storage disease, amyloidosis, primary biliary cirrhosis, sclerosing cholangitis or any primary or secondary hepatic tumor.
- Current alcohol/substance abuse or mean alcohol consumption greater than 24g/day over past year.
- Use of growth hormone, prednisone or other anabolic agents (except for physiologic testosterone replacement) currently or within the past 6 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.
- Known history of insulin secreting tumor or symptomatic hypoglycemia.
- Current use or a history of treatment with interleukin-2, interferon-alpha, or other investigational agent(s) within the past 6 months. (This does not pertain to ARV's obtained through expanded access).
- Any medical condition for which the investigator believes a liver biopsy may be contraindicated.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Pioglitazone for Hepatic Steatosis in HIV
This study will determine whether pioglitazone (Actos, a drug approved to treat diabetes, can benefit HIV-infected people with fatty liver. Fatty changes of the liver (also known as steatosis) have been linked to diabetes and long-term liver damage in some patients. Pioglitazone has been shown to improve fatty liver in people without HIV; this study will see if it is beneficial for people with HIV as well.
HIV-infected patients 18 years of age and older with increased fat in the liver may be eligible for this study. Screening includes a CT scan and liver biopsy (withdrawal of a small sample of liver tissue through a needle).
Read more
Participants are randomly assigned to take either 45 mg of pioglitazone or placebo (sugar pill) by mouth once a day for 48 weeks. At the end of 48 weeks, all participants stop taking their medication and are followed for an additional 48 weeks to see what, if any benefits, of pioglitazone persist after treatment is stopped. In addition to taking the study medication, participants undergo the following procedures:
- Visits to the NIH Clinical Center over a period of approximately 2 years at day 0 and weeks 2, 8, 16, 24, 32, 40, 48, 52, 72, and 96. Most visits take about 1 hour and include blood drawing for various laboratory tests.
- Insulin clamp test at day 0 and weeks 24 and 48 to see how the body processes glucose. This test takes 4 to 6 hours and may include an overnight stay at the Clinical Center. A catheter (plastic tube) is placed in a vein in the arm to infuse insulin and another is placed in a vein on the back of the hand to draw blood samples. Blood sugar is checked frequently and glucose is given to keep blood sugar at normal values.
- Nutrition evaluations at day 0 and weeks 24 and 48. Subjects write down all the food they eat and drink for 4 days before the visit. They meet with a nutritionist to review the food record and to complete simple measurements of body fat and shape.
- CT scan of liver and abdomen at weeks 24, 48, 72 and 96.
- Liver biopsy at week 48.
Read the detailed description
While the introduction of antiretroviral therapy for HIV/AIDS has transformed HIV disease into a chronic infection for many, the use of antiretroviral therapy is also often associated with metabolic abnormalities including insulin resistance, central fat accumulation and peripheral fat atrophy. Fatty infiltration of the liver or hepatic steatosis may be an important consequence of these metabolic derangements or may represent a direct toxicity associated with HIV infection and/or antiretroviral medications. Preliminary data suggests that hepatic steatosis may be very common and perhaps present in up to 50 percent of HIV-infected patients receiving antiretroviral therapy. Hepatic steatosis represents one step in the potential progression towards hepatocellular injury, non-alcoholic steatohepatitis (NASH), and, in a small percentage of patients, subsequent fibrosis and cirrhosis. In addition, hepatic fat content is closely associated with impaired insulin resistance and type 2 diabetes, conditions increasingly recognized among HIV-infected patients. In the setting of type 2 diabetes mellitus and NASH, thiazolidinediones such as pioglitazone, have been shown to reduce hepatic steatosis, lower transaminase levels and improve insulin sensitivity.
In order to determine the potential benefits of pioglitazone therapy in the setting of HIV infection and hepatic steatosis, we will conduct a 96-week, double-blind, randomized placebo controlled trial of pioglitazone (45 mg/day) in 50 HIV-infected men and women, with 48 weeks of active treatment and 48 weeks of observational follow-up after study treatment ends. We anticipate needing to screen 100 subjects to identify a sufficient number of eligible participants to enroll in the study. The primary outcome variable of interest in this trial will be the change in hepatic fat score, liver-to-spleen ratio, which is calculated from CT scan of the abdomen. Important secondary outcomes will be histologic improvement on liver biopsy performed at baseline and 48 weeks, as well as improvements in transaminase levels and insulin sensitivity measured by hyperinsulinemic euglycemic clamp. All participants will be followed for 48 weeks after discontinuing study treatment to evaluate the short-term natural history of steatosis in those who received placebo and to assess the durability of any potential benefits of pioglitazone upon withdrawal. In this way, important information about the efficacy of pioglitazone to treat hepatic steatosis and improve the metabolic profile in HIV-infected patients will be obtained, as well as preliminary data on whether benefits of pioglitazone are sustained after treatment is discontinued.
- Conditions
- HIV Infections, Hepatic Steatosis, Insulin Resistance
- Being tested
- Pioglitazone
- Keywords
- Pioglitazone, Hepatic Steatosis, Liver Toxicity, Liver Biopsy, HIV, Treatment Experienced, Treatment Naive
- Medical subject headings
- HIV Infections, Fatty Liver, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic Steatosis
Evaluation of the safety and potential benefits of pioglitazone therapy on hepatic steatosis in HIV-infected men and women.
Measured: 96 weeks
Secondary outcomes (1)
Insulin Resistance
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2007 (estimated)
- Study startFeb 2007
- Primary completionOct 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00441272
- Sponsor's protocol ID
- 070105
- Other IDs
- 07-I-0105
- Status last verified
- Oct 2008
- First submitted
- 27 Feb 2007
- Last updated
- 19 Feb 2010
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 12684916Carr A, Samaras K, Chisholm DJ, Cooper DA. Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet. 1998 Jun 20;351(9119):1881-3. doi: 10.1016/S0140-6736(98)03391-1.
PubMed 9652687Carr A, Miller J, Law M, Cooper DA. A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome. AIDS. 2000 Feb 18;14(3):F25-32. doi: 10.1097/00002030-200002180-00001.
PubMed 10716495
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pioglitazone for Hepatic Steatosis in HIV
- ClinicalTrials.gov ID
- NCT00441272
- Acronym / sponsor ID
- 070105
- Conditions
- HIV Infections, Hepatic Steatosis, Insulin Resistance
- Keywords
- Pioglitazone, Hepatic Steatosis, Liver Toxicity, Liver Biopsy, HIV, Treatment Experienced, Treatment Naive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Feb 2007
- Primary completion
- Oct 2008 (actual)
- First posted
- 28 Feb 2007 (estimated)
- Results
- Posted 19 Feb 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will determine whether pioglitazone (Actos, a drug approved to treat diabetes, can benefit HIV-infected people with fatty liver. Fatty changes of the liver (also known as steatosis) have been linked to diabetes and long-term liver damage in some patients. Pioglitazone has been shown to improve fatty liver in people without HIV; this study will see if it is beneficial for people with HIV as well.
HIV-infected patients 18 years of age and older with increased fat in the liver may be eligible for this study. Screening includes a CT scan and liver biopsy (withdrawal of a small sample of liver tissue through a needle).
Participants are randomly assigned to take either 45 mg of pioglitazone or placebo (sugar pill) by mouth once a day for 48 weeks. At the end of 48 weeks, all participants stop taking their medication and are followed for an additional 48 weeks to see what, if any benefits, of pioglitazone persist after treatment is stopped. In addition to taking the study medication, participants undergo the following procedures:
- Visits to the NIH Clinical Center over a period of approximately 2 years at day 0 and weeks 2, 8, 16, 24, 32, 40, 48, 52, 72, and 96. Most visits take about 1 hour and include blood drawing for various laboratory tests.
- Insulin clamp test at day 0 and weeks 24 and 48 to see how the body processes glucose. This test takes 4 to 6 hours and may include an overnight stay at the Clinical Center. A catheter (plastic tube) is placed in a vein in the arm to infuse insulin and another is placed in a vein on the back of the hand to draw blood samples. Blood sugar is checked frequently and glucose is given to keep blood sugar at normal values.
- Nutrition evaluations at day 0 and weeks 24 and 48. Subjects write down all the food they eat and drink for 4 days before the visit. They meet with a nutritionist to review the food record and to complete simple measurements of body fat and shape.
- CT scan of liver and abdomen at weeks 24, 48, 72 and 96.
- Liver biopsy at week 48.
Detailed description
While the introduction of antiretroviral therapy for HIV/AIDS has transformed HIV disease into a chronic infection for many, the use of antiretroviral therapy is also often associated with metabolic abnormalities including insulin resistance, central fat accumulation and peripheral fat atrophy. Fatty infiltration of the liver or hepatic steatosis may be an important consequence of these metabolic derangements or may represent a direct toxicity associated with HIV infection and/or antiretroviral medications. Preliminary data suggests that hepatic steatosis may be very common and perhaps present in up to 50 percent of HIV-infected patients receiving antiretroviral therapy. Hepatic steatosis represents one step in the potential progression towards hepatocellular injury, non-alcoholic steatohepatitis (NASH), and, in a small percentage of patients, subsequent fibrosis and cirrhosis. In addition, hepatic fat content is closely associated with impaired insulin resistance and type 2 diabetes, conditions increasingly recognized among HIV-infected patients. In the setting of type 2 diabetes mellitus and NASH, thiazolidinediones such as pioglitazone, have been shown to reduce hepatic steatosis, lower transaminase levels and improve insulin sensitivity.
In order to determine the potential benefits of pioglitazone therapy in the setting of HIV infection and hepatic steatosis, we will conduct a 96-week, double-blind, randomized placebo controlled trial of pioglitazone (45 mg/day) in 50 HIV-infected men and women, with 48 weeks of active treatment and 48 weeks of observational follow-up after study treatment ends. We anticipate needing to screen 100 subjects to identify a sufficient number of eligible participants to enroll in the study. The primary outcome variable of interest in this trial will be the change in hepatic fat score, liver-to-spleen ratio, which is calculated from CT scan of the abdomen. Important secondary outcomes will be histologic improvement on liver biopsy performed at baseline and 48 weeks, as well as improvements in transaminase levels and insulin sensitivity measured by hyperinsulinemic euglycemic clamp. All participants will be followed for 48 weeks after discontinuing study treatment to evaluate the short-term natural history of steatosis in those who received placebo and to assess the durability of any potential benefits of pioglitazone upon withdrawal. In this way, important information about the efficacy of pioglitazone to treat hepatic steatosis and improve the metabolic profile in HIV-infected patients will be obtained, as well as preliminary data on whether benefits of pioglitazone are sustained after treatment is discontinued.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
Key exclusion criteria (18 listed)
- 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.
- MELD score greater than 9 or previously diagnosed cirrhosis.
- ALT greater than 3 times the upper limit of normal.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pioglitazone | Drug | – |
Primary outcome
Hepatic Steatosis
Time frame: 96 weeks
Evaluation of the safety and potential benefits of pioglitazone therapy on hepatic steatosis in HIV-infected men and women.
1 secondary outcome
Insulin Resistance
Time frame: 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2010.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12684916Jain 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.
- Background: PubMed 9652687Carr A, Samaras K, Chisholm DJ, Cooper DA. Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet. 1998 Jun 20;351(9119):1881-3. doi: 10.1016/S0140-6736(98)03391-1.
- Background: PubMed 10716495Carr A, Miller J, Law M, Cooper DA. A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome. AIDS. 2000 Feb 18;14(3):F25-32. doi: 10.1097/00002030-200002180-00001.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pioglitazone in people with HIV Infections and Hepatic Steatosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Feb 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Feb 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hepatic Steatosis (time frame: 96 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00441272, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2010.