Nonalcoholic SteatohepatitisPhase 2/3NCT00267670
Pentoxifylline/Nonalcoholic Steatohepatitis (NASH) Study: The Effect of Pentoxifylline on NASH
A Phase 2/3 study testing Pentoxifylline in people with Nonalcoholic Steatohepatitis and Liver Diseases, run by Northwestern University at 1 site in United States.
Trial summary
The purpose of this study is to explore the potential benefit of the medication, pentoxifylline, for the treatment of NASH. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Nonalcoholic Steatohepatitis, Liver Diseases
- What is being tested?
- Pentoxifylline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2005to Sep 2009
- Phase
- Phase 2/3
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must be willing to give written informed consent
- Diagnosis of steatohepatitis Grade >= 1 (Brunt et al. criteria - Am J Gastroenterology 1999;94(9)2467-74) on biopsy within 6 months prior to entry into protocol
- No histologic evidence of cirrhosis
- Persistent ALT elevation (> 1.5 the upper limit normal) over 6 months prior to entry into study
- Adult subjects 18-65 years of age of any race or gender
- Compensated liver disease with the following hematologic, biochemical, and serological criteria on entry into protocol:
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- Hemoglobin > 11 gm/dL for females and > 12 gm/dL for males
- White blood cell (WBC) > 2.5 K/UL
- Neutrophil count > 1.5 K/UL
- Platelets > 100 K/UL
- Direct bilirubin, within normal limits
- Indirect bilirubin within normal limits (unless non-hepatitis factors such as Gilbert's disease explain indirect bilirubin rise. In such cases total bilirubin must be < 3.0 mg/dL)
- Albumin > 3.2 g/dL
- Serum creatinine within normal limits
- Hemoglobin A1c (HgbA1c) < 7%
- Antinuclear antibodies (ANA) < 1:160
- Anti-smooth muscle Ab negative
- Serum hepatitis B surface antigen (HepBsAg) negative
- Serum hepatitis C antibody (HepC Ab) negative
- Iron/total iron binding capacity (TIBC) ratio (transferrin saturation) < 45%
- Alpha-1-antitrypsin level within normal limits
- Ceruloplasmin level within normal limits
- Negative pregnancy test (females)
- Concomitant use of lipid lowering agents at study entry will not exclude patients from the study.
Who cannot join
- Evidence of decompensated cirrhosis
- Active gastrointestinal (GI) bleeding
- Renal failure (creatinine clearance < 80 mL/min)
- Active alcohol or drug abuse
- Uncontrolled diabetes (HgbA1c > 7)
- Current treatment with anti-diabetic medications such as thiazolidinediones or metformin (stable doses of sulfonylureas are acceptable)
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- Current treatment with anti-TNF alpha medication (i.e. Remicade or Enbrel)
- Current treatment with vitamin E
- Alcohol consumption < 20 g/day (males) or < 10 g/day (females) - assessed by one physician and confirmed with one family member.
- HIV positive status
- Any history of cerebral and/or retinal hemorrhage
- Prior intolerance of pentoxifylline or any other methylxanthine (i.e. caffeine, theophylline, or theobromine)
- Current use of theophylline
- Known diagnosis of malignancy
- Any other conditions which the investigator feels would make the subject unsuitable for enrollment, or could interfere with the subject completing the protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Pentoxifylline on Nonalcoholic Steatohepatitis (NASH)
The purpose of this study is to explore the potential benefit of the medication, pentoxifylline, for the treatment of NASH.
Read the detailed description
This is an investigational study looking at subjects who have been diagnosed with nonalcoholic steatohepatitis (NASH) or 'fatty liver disease'. There is currently no FDA approved available treatment for NASH. The purpose of this study is to explore the potential benefit of the medication, pentoxifylline, for the treatment of NASH. The effectiveness of this drug will be determined by taking blood samples and a liver biopsy. To determine if there is any effect of the medication, two-thirds of the patients participating in the study will receive pentoxifylline and one-third will receive placebo (sugar pill). Thus, an individual's chance of receiving the drug is 67%. In addition to receiving a study drug (placebo or pentoxifylline) the subjects will be encouraged to achieve modest weight loss (~1-2 lbs/week) via low-fat diet and exercise.
The drug (Pentoxifylline) being studied is not approved for use in people who have NASH. Pentoxifylline is considered experimental in this study. Pentoxifylline has been safely used for the treatment of other medical conditions such as alcohol related liver disease and poor circulation. Pentoxifylline is a pill which is taken three times a day.
- Conditions
- Nonalcoholic Steatohepatitis, Liver Diseases
- Being tested
- Pentoxifylline, Placebo
- Keywords
- Fatty Liver Disease, Liver, NASH, Nonalcoholic Steatohepatitis, Nonalcoholic Fatty Liver Disease (NAFLD), Pentoxifylline
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PentoxifyllineDrug
Also called Trental
400mg PO TID
PlaceboDrug
Also called sugar pill
1 pill PO TID
| Study group | Role | What they receive |
|---|---|---|
| Pentoxifylline | Experimental | 400mg PO TID Receives: Drug: Pentoxifylline |
| Placebo | Placebo comparator | 1 pill PO TID Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Participants With a 30% Reduction in Alanine Aminotransferase (ALT) Treated With Pentoxifylline (PTX) or Placebo for 12 Months.
The primary goal of the study was to determine whether pentoxifylline (PTX) therapy improved serum ALT (> or = 30% change from baseline to month 12) compared to placebo.
Measured: baseline and 12 months
Secondary outcomes (3)
The Effect of Pentoxifylline on Change in Tumor Necrosis Factor [TNF]-α Levels in Patients With NASH
The mean change from baseline to month 12 in proinflammatory cytokines (such as TNF-α) and gene expresssion were the secondary endpoints and were analyzed with the same analysis of covariance model and summary statistics specified for the primary endpoint. Differences were regarded as statistically significant when P < 0.05. The results for TNF-α are reported here. Interleukin-6 [IL-6], IL-10) and expression of TNF-alpha Receptors (p55 and p75) had insufficient data for statistical analysis.
Measured: one year
Change in Serum Leptin Levels in Patients Treated With Pentoxifylline or Placebo for 12 Months
Values represent changes in leptin from baseline to 12 months in patients treated with pentoxifylline or placebo.
Measured: baseline and one year
Change in Serum Adiponectin Levels in Patients Treated With Pentoxifylline or Placebo for 12 Months
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2005 (estimated)
- Study startMar 2005
- Primary completionSep 2009
- Study completionSep 2009
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.
- More trials run by Northwestern UniversityThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mary Rinella, Northwestern University
- Investigators
- Mary E Rinella, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00267670
- Sponsor's protocol ID
- IRB # 1347-001
- Other IDs
- GCRC Protocol #891
- Status last verified
- Aug 2014
- First submitted
- 12 Dec 2005
- Last updated
- 9 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Van Wagner LB, Koppe SW, Brunt EM, Gottstein J, Gardikiotes K, Green RM, Rinella ME. Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial. Ann Hepatol. 2011 Jul-Sep;10(3):277-86.
PubMed 21677329
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Pentoxifylline on Nonalcoholic Steatohepatitis (NASH)
- ClinicalTrials.gov ID
- NCT00267670
- Acronym / sponsor ID
- IRB # 1347-001
- Conditions
- Nonalcoholic Steatohepatitis, Liver Diseases
- Keywords
- Fatty Liver Disease, Liver, NASH, Nonalcoholic Steatohepatitis, Nonalcoholic Fatty Liver Disease (NAFLD), Pentoxifylline
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Mar 2005
- Primary completion
- Sep 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 21 Dec 2005 (estimated)
- Results
- Posted 9 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to explore the potential benefit of the medication, pentoxifylline, for the treatment of NASH.
Detailed description
This is an investigational study looking at subjects who have been diagnosed with nonalcoholic steatohepatitis (NASH) or 'fatty liver disease'. There is currently no FDA approved available treatment for NASH. The purpose of this study is to explore the potential benefit of the medication, pentoxifylline, for the treatment of NASH. The effectiveness of this drug will be determined by taking blood samples and a liver biopsy. To determine if there is any effect of the medication, two-thirds of the patients participating in the study will receive pentoxifylline and one-third will receive placebo (sugar pill). Thus, an individual's chance of receiving the drug is 67%. In addition to receiving a study drug (placebo or pentoxifylline) the subjects will be encouraged to achieve modest weight loss (~1-2 lbs/week) via low-fat diet and exercise.
The drug (Pentoxifylline) being studied is not approved for use in people who have NASH. Pentoxifylline is considered experimental in this study. Pentoxifylline has been safely used for the treatment of other medical conditions such as alcohol related liver disease and poor circulation. Pentoxifylline is a pill which is taken three times a day.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pentoxifylline | Experimental | Drug: Pentoxifylline400mg PO TID |
| Placebo | Placebo comparator | Drug: Placebo1 pill PO TID |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Subjects must be willing to give written informed consent
- Diagnosis of steatohepatitis Grade >= 1 (Brunt et al. criteria - Am J Gastroenterology 1999;94(9)2467-74) on biopsy within 6 months prior to entry into protocol
- No histologic evidence of cirrhosis
- Persistent ALT elevation (> 1.5 the upper limit normal) over 6 months prior to entry into study
- Adult subjects 18-65 years of age of any race or gender
Key exclusion criteria (15 listed)
- Evidence of decompensated cirrhosis
- Active gastrointestinal (GI) bleeding
- Renal failure (creatinine clearance < 80 mL/min)
- Active alcohol or drug abuse
- Uncontrolled diabetes (HgbA1c > 7)
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 |
|---|---|---|
| PentoxifyllineAlso: Trental400mg PO TID | Drug | Pentoxifylline |
| PlaceboAlso: sugar pill1 pill PO TID | Drug | Placebo |
Primary outcome
The Number of Participants With a 30% Reduction in Alanine Aminotransferase (ALT) Treated With Pentoxifylline (PTX) or Placebo for 12 Months.
Time frame: baseline and 12 months
The primary goal of the study was to determine whether pentoxifylline (PTX) therapy improved serum ALT (> or = 30% change from baseline to month 12) compared to placebo.
3 secondary outcomes
The Effect of Pentoxifylline on Change in Tumor Necrosis Factor [TNF]-α Levels in Patients With NASH
Time frame: one year
Change in Serum Leptin Levels in Patients Treated With Pentoxifylline or Placebo for 12 Months
Time frame: baseline and one year
Change in Serum Adiponectin Levels in Patients Treated With Pentoxifylline or Placebo for 12 Months
Time frame: one year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21677329Van Wagner LB, Koppe SW, Brunt EM, Gottstein J, Gardikiotes K, Green RM, Rinella ME. Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial. Ann Hepatol. 2011 Jul-Sep;10(3):277-86.
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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.
Mary E Rinella, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Pentoxifylline in people with Nonalcoholic Steatohepatitis and Liver Diseases, run by Northwestern University 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 24 inclusion and 15 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 9 Sep 2014. 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. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 9 Sep 2014). 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?
The Number of Participants With a 30% Reduction in Alanine Aminotransferase (ALT) Treated With Pentoxifylline (PTX) or Placebo for 12 Months. (time frame: baseline and 12 months). 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 NCT00267670, 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 9 Sep 2014.