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

NCT00845845 | Terminated Phase 2 Results

• 1 other identifier: 2003-0601
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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).

Conditions

Nonalcoholic Steatohepatitis (NASH); Hepatic Steatosis

Keywords

Non-alcoholic steatohepatitis; Omega-3 fatty acids; MRI; NASH

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Magnetic Resonance Imaging (MRI) as an Assessment of Hepatic Steatosis in Patients With Biopsy-proven Nonalcoholic Steatohepatitis (NASH)

  24 weeks

Study Arms (2)

Omega-3-acid ethyl esters (Lovaza)

ACTIVE COMPARATOR

Participants receive 4 milligrams (mg) daily of omega-3-acid ethyl esters (Lovaza) and dietary counseling for 24 weeks

Drug: Omega-3-acid ethyl esters (Lovaza)

Placebo

PLACEBO COMPARATOR

Participants receive daily placebo and dietary counseling for 24 weeks

Drug: Placebo

Interventions

Omega-3-acid ethyl esters (Lovaza) DRUG

4 milligrams daily omega-3-acid ethyl esters (Lovaza) with dietary counseling for 24 weeks.

Also known as: Lovaza

Omega-3-acid ethyl esters (Lovaza)

Placebo DRUG

Daily placebo with dietary counseling for 24 weeks.

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

The University of Illinois Chicago

Chicago, Illinois, 60612, United States

Location

Related Publications (20)

• Reid AE. Nonalcoholic steatohepatitis. Gastroenterology. 2001 Sep;121(3):710-23. doi: 10.1053/gast.2001.27126.

  PMID: 11522755 BACKGROUND

• Bacon BR, Farahvash MJ, Janney CG, Neuschwander-Tetri BA. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology. 1994 Oct;107(4):1103-9. doi: 10.1016/0016-5085(94)90235-6.

  PMID: 7523217 BACKGROUND

• 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. doi: 10.1053/jhep.2003.50229.

  PMID: 12774006 BACKGROUND

• 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. doi: 10.1002/hep.510290347.

  PMID: 10051466 BACKGROUND

• 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. doi: 10.1053/jhep.2002.36939.

  PMID: 12447858 BACKGROUND

• Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology. 2003 May;37(5):1202-19. doi: 10.1053/jhep.2003.50193.

  PMID: 12717402 BACKGROUND

• 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. doi: 10.1053/jhep.2003.50095.

  PMID: 12601351 BACKGROUND

• 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. doi: 10.1053/jhep.2003.50048.

  PMID: 12540784 BACKGROUND

• 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. doi: 10.1073/pnas.0630588100. Epub 2003 Mar 10.

  PMID: 12629214 BACKGROUND

• 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. doi: 10.1053/jhep.2002.32029.

  PMID: 11915021 BACKGROUND

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

  PMID: 10839868 BACKGROUND

• 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. doi: 10.1016/s0168-8278(03)00027-8.

  PMID: 12663234 BACKGROUND

• 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. doi: 10.1016/s0140-6736(01)06042-1.

  PMID: 11567710 BACKGROUND

• Kudo N, Kawashima Y. Fish oil-feeding prevents perfluorooctanoic acid-induced fatty liver in mice. Toxicol Appl Pharmacol. 1997 Aug;145(2):285-93. doi: 10.1006/taap.1997.8186.

  PMID: 9266801 BACKGROUND

• 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. doi: 10.1152/ajpendo.00414.2001.

  PMID: 11788372 BACKGROUND

• 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. doi: 10.1161/01.atv.0000038493.65177.94. No abstract available.

  PMID: 12588785 BACKGROUND

• 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. doi: 10.1079/BJN2002731.

  PMID: 12568661 BACKGROUND

• 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. doi: 10.1172/JCI5584.

  PMID: 10491416 BACKGROUND

• 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. doi: 10.2337/diab.43.9.1114.

  PMID: 8070611 BACKGROUND

• 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. doi: 10.1111/j.1572-0241.1999.01377.x.

  PMID: 10484010 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fatty Liver

Interventions

Omacor; Sugars

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Carbohydrates

Limitations and Caveats

The study was terminated on October 12, 2010 due to low enrollment. Consequently, no analyses were completed.

Results Point of Contact

• Title: Scott Cotler, M.D. Professor of Medicine
• Organization: The University of Illinois Chicago

scotler@lumc.edu

708-216-3789

Study Officials

• Scott Cotler, M.D.

  University of Illinois Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 17, 2009
• First Posted: February 18, 2009
• Study Start: March 1, 2006
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: July 24, 2013
• Results First Posted: July 24, 2013

Record last verified: 2013-06

Locations

US (1)