Nonalcoholic SteatohepatitisPhase 2NCT00590161
Pentoxifylline in Patients With Nonalcoholic Steatohepatitis
A Phase 2 study testing pentoxifylline (PTX) in people with Nonalcoholic Steatohepatitis, run by Case Western Reserve University at 3 sites in United States.
Trial summary
One third of the population in the United States has nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, can lead to cirrhosis.Currently, there is no proven therapy for patients with NASH. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Nonalcoholic Steatohepatitis
- What is being tested?
- pentoxifylline (PTX)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 55 participants
- Where
- 3 sitesUnited States
- Study dates
- Dec 2006to Dec 2010
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients ages 18 to 70 years.
- Liver biopsy compatible with NASH, including presence of steatosis and necroinflammatory activity on liver biopsy done during the prior 6 months to study enrollment
- Daily alcohol intake of <30 g for males and <15 g for females;
- Appropriate exclusion of other liver diseases.
- Patients with diabetes mellitus type 2 diagnosis as defined by a previous diagnosis of DM and current therapy with antidiabetic agents, or by fulfillment of 1997 American Diabetic Association (ADA) criteria, may be included if they fulfill the following criteria: (i) therapeutic regimen limited to specific oral agents including sulfonylureas (e.g. glipizide and glyburide) and/or biguanides (e.g. metformin); (ii) stable therapeutic regimen as defined by no changes in oral agents for at least 3 months; (iii) Hemoglobin A1C (HgbA1C) < 8.5 %.
Who cannot join
- History of past excessive alcohol drinking (as defined above) for a period longer than 2 years at any time in the past 10 years.
- Current consumption of alcohol >30 g daily for males and >15 g daily for females.
- Positive testing for hepatitis B surface antigen, hepatitis C virus antibody, or ribonucleic acid (RNA) of hepatitis C virus of deoxyribonucleic acid (DNA) of hepatitis B virus.
- Patients taking medications known to cause steatosis.
- Other causes of liver disease suspected by history, family interview, or laboratory testing.
- Patients with cirrhosis defined by stage 4 fibrosis on liver biopsy, or if the patient shows unequivocal clinical evidence of portal hypertension, such as thrombocytopenia, splenomegaly, or esophageal varices.
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- Patients taking medications of possible benefit in NASH within 3 months prior to the liver biopsy. These medications include Vitamin E, Betaine, S-adenosylmethionine (SAM-e), thiazolidinediones, and acarbose.
- Patients with diabetes mellitus who are on Insulin therapy.
- Patients with diabetes mellitus on therapy with thiazolidinediones or alpha-glucosidase inhibitors such as acarbose
- Hypersensitivity to pentoxifylline or the methylxanthines (caffeine, theophylline, theobromine).
- History of cerebral or retinal hemorrhage.
- Other medical comorbidities (such as cardiac, central nervous system, renal, cancer) that would interfere with completion of the study.
- Patients taking Theophylline or Coumadin because of potential drug-drug interactions with Pentoxifylline.
- Pregnant or nursing women.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Louis Stokes VA Medical Center
Cleveland, Ohio, 44106
Metrohealth Medical Center
Cleveland, Ohio, 44109
Cleveland Clinic
Cleveland, Ohio, 44195
About this study
Official title: Treatment Efficacy of Pentoxifylline in Patients With Nonalcoholic Steatohepatitis: A Double-blind Randomized Placebo Controlled Trial
One third of the population in the United States has nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, can lead to cirrhosis.Currently, there is no proven therapy for patients with NASH. The investigators core hypothesis is that therapy of patients with NASH with pentoxifylline (PTX) for one year will result in improvement of biochemical parameters of liver disease and hepatic histology. The focus of this proposal is on the effectiveness of pentoxifylline (PTX) in improving laboratory and tissue parameters of liver disease, parameters of insulin-resistance, and levels of cytokines in patients with NASH.
- Conditions
- Nonalcoholic Steatohepatitis
- Being tested
- pentoxifylline (PTX), placebo
- Keywords
- Fatty Liver, Nonalcoholic fatty liver disease (NALFD), NAFLD, Nonalcoholic steatohepatitis (NASH), NASH, pentoxifylline
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pentoxifylline (PTX)Drug
400 mg PO tid
placeboDrug
placebo tid
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Pentoxifylline (PTX) 400 mg by mouth (PO) three times daily (TID) Receives: Drug: pentoxifylline (PTX) |
| 2 | Placebo comparator | Placebo three times daily (TID) Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Histological Improvement of at Least 2 Points in NAFLD Activity Score (NAS) on Liver Biopsy After One Year.
The NAFLD Activity Score (NAS) grades NAFLD on liver biopsy based on the individual scoring of steatosis, inflammation and balloning. The NAS is assessed on a scale of 0 to 8 with higher scores indicating more severe disease and lower scores indicating less severe disease. NAS is obtained by adding steatosis(assessed on a scale of 0 to 3), inflammation (assessed on a scale of 0 to 3) and ballooning (assessed on a scale of 0 to 2).
Measured: 1 year (Baseline liver biopsy done at study entry, and subsequent liver biopsy done after one year of therapy with pentoxifylline or placebo)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2008 (estimated)
- Study startDec 2006
- Primary completionJul 2010
- Study completionDec 2010
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 (1)Papers the sponsor has linked to this study.
- Other trials for Nonalcoholic SteatohepatitisStudies of the same condition, open and under way.
- 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
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Western Reserve University
- Sponsor type
- University, hospital or other
- Collaborators
- American College of Gastroenterology
- Responsible party
- Principal investigator, Claudia Zein, Case Western Reserve University
- Investigators
- Claudia O Zein, MD, MSc, Principal investigator, Case Western Reserve University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00590161
- Sponsor's protocol ID
- R-1196 CWRU CRU
- Status last verified
- Aug 2013
- First submitted
- 26 Dec 2007
- Last updated
- 26 Sep 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Zein CO, Yerian LM, Gogate P, Lopez R, Kirwan JP, Feldstein AE, McCullough AJ. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology. 2011 Nov;54(5):1610-9. doi: 10.1002/hep.24544. Epub 2011 Aug 24.
PubMed 21748765
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment Efficacy of Pentoxifylline in Patients With Nonalcoholic Steatohepatitis: A Double-blind Randomized Placebo Controlled Trial
- ClinicalTrials.gov ID
- NCT00590161
- Acronym / sponsor ID
- R-1196 CWRU CRU
- Conditions
- Nonalcoholic Steatohepatitis
- Keywords
- Fatty Liver, Nonalcoholic fatty liver disease (NALFD), NAFLD, Nonalcoholic steatohepatitis (NASH), NASH, pentoxifylline
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Case Western Reserve UniversityUniversity, hospital or other
- Collaborators
- American College of Gastroenterology
- Study start
- Dec 2006
- Primary completion
- Jul 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 10 Jan 2008 (estimated)
- Results
- Posted 26 Sep 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
One third of the population in the United States has nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, can lead to cirrhosis.Currently, there is no proven therapy for patients with NASH. The investigators core hypothesis is that therapy of patients with NASH with pentoxifylline (PTX) for one year will result in improvement of biochemical parameters of liver disease and hepatic histology. The focus of this proposal is on the effectiveness of pentoxifylline (PTX) in improving laboratory and tissue parameters of liver disease, parameters of insulin-resistance, and levels of cytokines in patients with NASH.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: pentoxifylline (PTX)Pentoxifylline (PTX) 400 mg by mouth (PO) three times daily (TID) |
| 2 | Placebo comparator | Drug: placeboPlacebo three times daily (TID) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male and female patients ages 18 to 70 years.
- Liver biopsy compatible with NASH, including presence of steatosis and necroinflammatory activity on liver biopsy done during the prior 6 months to study enrollment
- Daily alcohol intake of <30 g for males and <15 g for females;
- Appropriate exclusion of other liver diseases.
- Patients with diabetes mellitus type 2 diagnosis as defined by a previous diagnosis of DM and current therapy with antidiabetic agents, or by fulfillment of 1997 American Diabetic Association (ADA) criteria, may be included if they fulfill the following criteria: (i) therapeutic regimen limited to specific oral agents including sulfonylureas (e.g. glipizide and glyburide) and/or biguanides (e.g. metformin); (ii) stable therapeutic regimen as defined by no changes in oral agents for at least 3 months; (iii) Hemoglobin A1C (HgbA1C) < 8.5 %.
Key exclusion criteria (14 listed)
- History of past excessive alcohol drinking (as defined above) for a period longer than 2 years at any time in the past 10 years.
- Current consumption of alcohol >30 g daily for males and >15 g daily for females.
- Positive testing for hepatitis B surface antigen, hepatitis C virus antibody, or ribonucleic acid (RNA) of hepatitis C virus of deoxyribonucleic acid (DNA) of hepatitis B virus.
- Patients taking medications known to cause steatosis.
- Other causes of liver disease suspected by history, family interview, or laboratory testing.
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 |
|---|---|---|
| pentoxifylline (PTX)400 mg PO tid | Drug | 1 |
| placeboplacebo tid | Drug | 2 |
Primary outcome
Histological Improvement of at Least 2 Points in NAFLD Activity Score (NAS) on Liver Biopsy After One Year.
Time frame: 1 year (Baseline liver biopsy done at study entry, and subsequent liver biopsy done after one year of therapy with pentoxifylline or placebo)
The NAFLD Activity Score (NAS) grades NAFLD on liver biopsy based on the individual scoring of steatosis, inflammation and balloning. The NAS is assessed on a scale of 0 to 8 with higher scores indicating more severe disease and lower scores indicating less severe disease. NAS is obtained by adding steatosis(assessed on a scale of 0 to 3), inflammation (assessed on a scale of 0 to 3) and ballooning (assessed on a scale of 0 to 2).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21748765Zein CO, Yerian LM, Gogate P, Lopez R, Kirwan JP, Feldstein AE, McCullough AJ. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology. 2011 Nov;54(5):1610-9. doi: 10.1002/hep.24544. Epub 2011 Aug 24.
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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.
Claudia O Zein, MD, MSc principal investigator
Case Western Reserve University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing pentoxifylline (PTX) in people with Nonalcoholic Steatohepatitis, run by Case Western Reserve University at 3 sites 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 5 inclusion and 14 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 26 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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. Some participants in this study may receive a placebo. 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 26 Sep 2013). 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?
Histological Improvement of at Least 2 Points in NAFLD Activity Score (NAS) on Liver Biopsy After One Year. (time frame: 1 year (Baseline liver biopsy done at study entry, and subsequent liver biopsy done after one year of therapy with pentoxifylline or placebo)). 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 NCT00590161, which also lists 1 linked publication.
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 26 Sep 2013.