Fish Oil and Diet for the Treatment of Non-Alcoholic Steatohepatitis (NASH)

Hepatic Steatosis Clinical Trial

Official title:

Fish Oil and Diet for the Treatment of Non-Alcoholic Steatohepatitis (NASH)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00845845
• Other study ID #: 2003-0601
• Status: Terminated
• Phase: Phase 2
• First received: February 17, 2009
• Last updated: June 18, 2013
• Start date: March 2006
• Est. completion date: October 2010

Study information

• Verified date: June 2013
• Source: University of Illinois at Chicago
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fatty Liver
• Hepatic Steatosis
• Nonalcoholic Steatohepatitis (NASH)

Intervention

Drug:
• Omega-3-acid ethyl esters (Lovaza)
4 milligrams daily omega-3-acid ethyl esters (Lovaza) with dietary counseling for 24 weeks.
• Placebo
Daily placebo with dietary counseling for 24 weeks.

Locations

Country	Name	City	State
United States	The University of Illinois Chicago	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Illinois at Chicago

Country where clinical trial is conducted

United States, 

References & Publications (20)

Bacon BR, Farahvash MJ, Janney CG, Neuschwander-Tetri BA. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology. 1994 Oct;107(4):1103-9. — View Citation

Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999 Sep;94(9):2467-74. — View Citation

Caldwell SH, Oelsner DH, Iezzoni JC, Hespenheide EE, Battle EH, Driscoll CJ. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology. 1999 Mar;29(3):664-9. — View Citation

Chalasani N, Gorski JC, Asghar MS, Asghar A, Foresman B, Hall SD, Crabb DW. Hepatic cytochrome P450 2E1 activity in nondiabetic patients with nonalcoholic steatohepatitis. Hepatology. 2003 Mar;37(3):544-50. — View Citation

Kris-Etherton PM, Harris WS, Appel LJ; Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):e20-30. Review. Erratum in: Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):e31.. — View Citation

Kudo N, Kawashima Y. Fish oil-feeding prevents perfluorooctanoic acid-induced fatty liver in mice. Toxicol Appl Pharmacol. 1997 Aug;145(2):285-93. — View Citation

Lavine JE. Vitamin E treatment of nonalcoholic steatohepatitis in children: a pilot study. J Pediatr. 2000 Jun;136(6):734-8. — View Citation

Li Z, Yang S, Lin H, Huang J, Watkins PA, Moser AB, Desimone C, Song XY, Diehl AM. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology. 2003 Feb;37(2):343-50. — View Citation

Listenberger LL, Han X, Lewis SE, Cases S, Farese RV Jr, Ory DS, Schaffer JE. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3077-82. Epub 2003 Mar 10. — View Citation

Marchesini G, Brizi M, Bianchi G, Tomassetti S, Zoli M, Melchionda N. Metformin in non-alcoholic steatohepatitis. Lancet. 2001 Sep 15;358(9285):893-4. — View Citation

Marrero JA, Fontana RJ, Su GL, Conjeevaram HS, Emick DM, Lok AS. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology. 2002 Dec;36(6):1349-54. — View Citation

Meagher EA, Barry OP, Burke A, Lucey MR, Lawson JA, Rokach J, FitzGerald GA. Alcohol-induced generation of lipid peroxidation products in humans. J Clin Invest. 1999 Sep;104(6):805-13. — View Citation

Mofrad P, Contos MJ, Haque M, Sargeant C, Fisher RA, Luketic VA, Sterling RK, Shiffman ML, Stravitz RT, Sanyal AJ. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology. 2003 Jun;37(6):1286-92. — View Citation

Neschen S, Moore I, Regittnig W, Yu CL, Wang Y, Pypaert M, Petersen KF, Shulman GI. Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue lipid content. Am J Physiol Endocrinol Metab. 2002 Feb;282(2):E395-401. — View Citation

Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Sponseller CA, Hampton K, Bacon BR. Interim results of a pilot study demonstrating the early effects of the PPAR-gamma ligand rosiglitazone on insulin sensitivity, aminotransferases, hepatic steatosis and body weight in patients with non-alcoholic steatohepatitis. J Hepatol. 2003 Apr;38(4):434-40. — View Citation

Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology. 2003 May;37(5):1202-19. Review. Erratum in: Hepatology. 2003 Aug;38(2):536. — View Citation

Reid AE. Nonalcoholic steatohepatitis. Gastroenterology. 2001 Sep;121(3):710-23. Review. — View Citation

Saad MF, Anderson RL, Laws A, Watanabe RM, Kades WW, Chen YD, Sands RE, Pei D, Savage PJ, Bergman RN. A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance. Insulin Resistance Atherosclerosis Study. Diabetes. 1994 Sep;43(9):1114-21. — View Citation

Saito M, Kubo K. Relationship between tissue lipid peroxidation and peroxidizability index after alpha-linolenic, eicosapentaenoic, or docosahexaenoic acid intake in rats. Br J Nutr. 2003 Jan;89(1):19-28. — View Citation

Saxena NK, Ikeda K, Rockey DC, Friedman SL, Anania FA. Leptin in hepatic fibrosis: evidence for increased collagen production in stellate cells and lean littermates of ob/ob mice. Hepatology. 2002 Apr;35(4):762-71. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Omega-3 Fatty Acid Supplementation and Its Effect on Hepatic Steatosis and Other Factors Associated With the Development of Nonalcoholic Steatohepatitis (NASH)		24 weeks	No
Secondary	Magnetic Resonance Imaging (MRI) as an Assessment of Hepatic Steatosis in Patients With Biopsy-proven Nonalcoholic Steatohepatitis (NASH)		24 weeks	No