Hepatic Steatosis, Nonalcoholic Steatohepatitis (NASH)
Conditions
Keywords
Non-alcoholic steatohepatitis, Omega-3 fatty acids, MRI, NASH
Brief summary
The current pilot study assesses the use of magnetic resonance imaging (MRI) to quantify hepatic steatosis. It will provide preliminary data regarding the use of omega-3 fatty acid supplementation (Lovaza) for the treatment of nonalcoholic steatohepatitis (NASH).
Interventions
DRUGOmega-3-acid ethyl esters (Lovaza)
4 milligrams daily omega-3-acid ethyl esters (Lovaza) with dietary counseling for 24 weeks.
DRUGPlacebo
Daily placebo with dietary counseling for 24 weeks.
Sponsors
University of Illinois at Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females at least 18 years of age. * Evidence of nonalcoholic steatohepatitis (NASH) on a liver biopsy performed within six months of entry to this study. * Laboratory parameters indicative of decompensated liver disease including: * bilirubin less than 2 milligrams/decilitre (mg/dl). * stable albumin within normal limits. * prothrombin time less than 3 seconds prolonged. * Serum creatinine less than 1.5 times the upper limit of normal. * Diabetic patients must be stable on oral medication for diabetes or have had less than a 10 percent change in their insulin dose over the past two months. * Thyroid stimulating hormone (TSH) or Free Thyroxine Index (FTI) within the normal range. * Hepatitis C antibody negative. * Hepatitis B Surface Antigen (HBsAg) seronegative. * Antinuclear antibody (ANA) less than 1:320. * Patient provides written informed consent.
Exclusion criteria
* Alcohol use exceeding 10 to 29 grams per day during the past six months. * Evidence of a cause of liver disease other than nonalcoholic steatohepatitis (NASH) on liver biopsy including: viral hepatitis, alcoholic liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, or recent hepatoxic drug exposure. * Patients with cirrhosis. * Use of medications commonly associated with nonalcoholic steatohepatitis (NASH) including: glucocorticoids, estrogens, tamoxifen, methotrexate, nifedipine, diltiazem, chloroquine, isoniazid, or amiodarone within the past six months. * Use of non-steroidal antiinflammatory drugs, fibrates (fenofibrate or gemfibrozil) or warfarin within one month of entering the study. * Uncontrolled diabetes, defined as a glycated hemoglobin (A1C) level greater than 8%. * Patients with insulin-dependent diabetes. * History of jejunal-ileal bypass or extensive small bowel resection. * Substance abuse including, but not limited to, alcohol or intravenous and inhaled drugs within the past six months. * Use of chemotherapy within six months of enrollment. * Patients taking metformin. * Thyroid abnormality in which normal thyroid function cannot be maintained by medication. * Pregnancy, females who are breastfeeding. * Solid organ transplant recipient. * History of a medical condition, which could interfere with participation in and completion of the protocol. * Use of oral supplements of Vitamin E within one month of enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Omega-3 Fatty Acid Supplementation and Its Effect on Hepatic Steatosis and Other Factors Associated With the Development of Nonalcoholic Steatohepatitis (NASH) | 24 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Magnetic Resonance Imaging (MRI) as an Assessment of Hepatic Steatosis in Patients With Biopsy-proven Nonalcoholic Steatohepatitis (NASH) | 24 weeks |
Countries
United States
Participant flow
Recruitment details
Twelve (12) individuals consented and were screened and nine (9) were randomized between March 2006 and June 2009. Due to low enrollment, the study was terminated in October 2010. Participants were recruited by study staff at outpatient clinics at The University of Illinois Chicago Hospitals and Clinics (UIHC).
Pre-assignment details
A screening evaluation was used prior to group assignment to evaluate whether patients were affected by nonalcoholic steatohepatitis (NASH) and to evaluate the inclusion and exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Omega-3-acid Ethyl Esters (Lovaza) Participants receive 4 milligrams (mg) daily of omega-3-acid ethyl esters (Lovaza) and dietary counseling for 24 weeks | 3 |
| Placebo Participants receive daily placebo and dietary counseling for 24 weeks | 6 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 4 |
Baseline characteristics
| Characteristic | Omega-3-acid Ethyl Esters (Lovaza) | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 6 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 3 participants | 6 participants | 9 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 3 | 0 / 6 |
| serious Total, serious adverse events | 1 / 3 | 0 / 6 |
Outcome results
Primary
Omega-3 Fatty Acid Supplementation and Its Effect on Hepatic Steatosis and Other Factors Associated With the Development of Nonalcoholic Steatohepatitis (NASH)
Time frame: 24 weeks
Population: This study was terminated on October 12, 2010 due to low enrollment. Primary analyses were never completed.
Secondary
Magnetic Resonance Imaging (MRI) as an Assessment of Hepatic Steatosis in Patients With Biopsy-proven Nonalcoholic Steatohepatitis (NASH)
Time frame: 24 weeks
Population: This study was terminated on October 12, 2010 due to low enrollment. Primary analyses were never completed.