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| ID | Type | Description | Link |
|---|---|---|---|
| GCRC Protocol #891 | Other Identifier | Northwestern University Clinical Research Center |
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The purpose of this study is to explore the potential benefit of the medication, pentoxifylline, for the treatment of NASH.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pentoxifylline | Experimental | 400mg PO TID |
|
| Placebo | Placebo Comparator | 1 pill PO TID |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pentoxifylline | Drug | 400mg PO TID |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | baseline and 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
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:
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.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mary E Rinella, MD | Northwestern University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern University | Chicago | Illinois | 60611 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21677329 | Derived | 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. |
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Subjects were excluded from the study if they had evidence of another form of liver disease or if they were HIV positive, pregnant or had evidence of ongoing alcohol consumption exceeding 20g(males) and 10g(females)daily. Furthermore, subjects were excluded if they were taking drugs known to cause steatohepatitis.
From March 2005 to March 2008 patients were recruited through the Northwestern Memorial Faculty Foundation Hepatology Clinic.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pentoxifylline | This group was given pentoxifylline 400mg thrice daily (tid) for 1 year |
| FG001 | Placebo | This group was given a capsule identical to pentoxifylline that contained sucrose. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Pentoxifylline | Patients in this group received pentoxifylline 400mg tid for 1 year. |
| BG001 | Placebo | Patients in this group received a capsule identical to pentoxifylline that instead contained sucrose. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The primary analysis was done as intention to treat. A secondary analysis was performed per protocol and there were no differences between the two analyses. Intention to treat results are reported. | Posted | Number | participants | baseline and 12 months |
|
Adverse events data were collected for 1 year for the duration of the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pentoxifylline | Patients in this group received pentoxifylline 400mg tid for 1 year. |
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The most significant limitation of this study is the small sample size, thus the lack of statistical significance may be due to low power.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mary E. Rinella, MD | Northwestern University | 312-503-4592 | m-rinella@northwestern.edu |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| D008107 | Liver Diseases |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D010431 | Pentoxifylline |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D013805 | Theobromine |
| D014970 | Xanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 |
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| Placebo | Drug | 1 pill PO TID |
|
|
| 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. | baseline and one year |
| Change in Serum Adiponectin Levels in Patients Treated With Pentoxifylline or Placebo for 12 Months | one year |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Patients in this group received a capsule identical to pentoxifylline that instead contained sucrose.
|
|
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| Secondary | 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. | Intention to Treat with last observation carried forward | Posted | Mean | Standard Error | pg/dL | one year |
|
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|
|
| Secondary | 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. | Posted | Mean | Standard Error | ng/mL | baseline and one year |
|
|
|
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| Secondary | Change in Serum Adiponectin Levels in Patients Treated With Pentoxifylline or Placebo for 12 Months | Posted | Mean | Standard Error | ug/mL | one year |
|
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| 0 |
| 19 |
| 0 |
| 19 |
| EG001 | Placebo | Patients in this group received a capsule identical to pentoxifylline that instead contained sucrose thrice daily for 1 year. | 0 | 7 | 0 | 7 |
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| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D002241 | Carbohydrates |