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

• Sponsor: University of Illinois at Chicago (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00845845
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arms: 2
• Duration (Months): 55
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Nonalcoholic Steatohepatitis (NASH); Hepatic Steatosis	Drug: Omega-3-acid ethyl esters (Lovaza); Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Fish Oil and Diet for the Treatment of Non-Alcoholic Steatohepatitis (NASH)
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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	Drug: Omega-3-acid ethyl esters (Lovaza); 4 milligrams daily omega-3-acid ethyl esters (Lovaza) with dietary counseling for 24 weeks.; Other Names: Lovaza
Placebo Comparator: Placebo Participants receive daily placebo and dietary counseling for 24 weeks	Drug: Placebo; Daily placebo with dietary counseling for 24 weeks.; Other Names: Sugar pill

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

1. Magnetic Resonance Imaging (MRI) as an Assessment of Hepatic Steatosis in Patients With Biopsy-proven Nonalcoholic Steatohepatitis (NASH) [24 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Illinois Chicago	Chicago	Illinois	United States	60612

Sponsors and Collaborators

• University of Illinois at Chicago

Investigators

• Principal Investigator: Scott Cotler, M.D., University of Illinois Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

• Bacon BR, Farahvash MJ, Janney CG, Neuschwander-Tetri BA. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology. 1994 Oct;107(4):1103-9.
• 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.
• 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.
• 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.
• 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..
• Kudo N, Kawashima Y. Fish oil-feeding prevents perfluorooctanoic acid-induced fatty liver in mice. Toxicol Appl Pharmacol. 1997 Aug;145(2):285-93.
• Lavine JE. Vitamin E treatment of nonalcoholic steatohepatitis in children: a pilot study. J Pediatr. 2000 Jun;136(6):734-8.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Reid AE. Nonalcoholic steatohepatitis. Gastroenterology. 2001 Sep;121(3):710-23. Review.
• 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.
• 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.
• 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.

• Responsible Party: Scott Cotler, MD, Professor of Medicine, University of Illinois at Chicago
• ClinicalTrials.gov Identifier: NCT00845845
• Other Study ID Numbers: 2003-0601
• First Posted: Feb 18, 2009
• Last Update Posted: Jul 24, 2013
• Last Verified: Jun 1, 2013

• Keywords provided by Scott Cotler, MD, Professor of Medicine, University of Illinois at Chicago: Non-alcoholic steatohepatitis; Omega-3 fatty acids; MRI; NASH
• Additional relevant MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease

Study Results

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 Detail	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.

Arm/Group Title	Omega-3-acid Ethyl Esters (Lovaza)	Placebo
Arm/Group Description	Participants receive 4 milligrams (mg) daily of omega-3-acid ethyl esters (Lovaza) and dietary counseling for 24 weeks	Participants receive daily placebo and dietary counseling for 24 weeks
Period Title: Overall Study
STARTED	3	6
COMPLETED	3	2
NOT COMPLETED	0	4

Baseline Characteristics

Arm/Group Title	Omega-3-acid Ethyl Esters (Lovaza)	Placebo	Total
Arm/Group Description	Participants receive 4 milligrams (mg) daily of omega-3-acid ethyl esters (Lovaza) and dietary counseling for 24 weeks	Participants receive daily placebo and dietary counseling for 24 weeks	Total of all reporting groups
Overall Participants	3	6	9
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	6 100%	9 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	2 66.7%	2 33.3%	4 44.4%
Male	1 33.3%	4 66.7%	5 55.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 33.3%	2 33.3%	3 33.3%
Not Hispanic or Latino	2 66.7%	4 66.7%	6 66.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%	6 100%	9 100%

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

This study was terminated on October 12, 2010 due to low enrollment. Primary analyses were never completed.

Arm/Group Title	Omega-3-acid Ethyl Esters (Lovaza)	Placebo
Arm/Group Description	Participants receive 4 milligrams (mg) daily of omega-3-acid ethyl esters (Lovaza) and dietary counseling for 24 weeks	Participants receive daily placebo and dietary counseling for 24 weeks
Measure Participants	0	0

2. Secondary Outcome

Title	Magnetic Resonance Imaging (MRI) as an Assessment of Hepatic Steatosis in Patients With Biopsy-proven Nonalcoholic Steatohepatitis (NASH)
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

This study was terminated on October 12, 2010 due to low enrollment. Primary analyses were never completed.

Arm/Group Title	Omega-3-acid Ethyl Esters (Lovaza)	Placebo
Arm/Group Description	Participants receive 4 milligrams (mg) daily of omega-3-acid ethyl esters (Lovaza) and dietary counseling for 24 weeks	Participants receive daily placebo and dietary counseling for 24 weeks
Measure Participants	0	0

Adverse Events

Time Frame	Adverse events were captured using a systematic assessment from baseline (week 0) through week 24 for both the treatment and placebo groups.
Arm/Group Title	Omega-3-acid Ethyl Esters (Lovaza)		Placebo
Arm/Group Description	Participants receive 4 milligrams (mg) daily of omega-3-acid ethyl esters (Lovaza) and dietary counseling for 24 weeks		Participants receive daily placebo and dietary counseling for 24 weeks
All Cause Mortality
	Omega-3-acid Ethyl Esters (Lovaza)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Omega-3-acid Ethyl Esters (Lovaza)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		0/6 (0%)
Infections and infestations
Herpes zoster	1/3 (33.3%)	1	0/6 (0%)	0
Other (Not Including Serious) Adverse Events
	Omega-3-acid Ethyl Esters (Lovaza)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		0/6 (0%)
Gastrointestinal disorders
Diarrhea	2/3 (66.7%)	2	0/6 (0%)	0

Limitations/Caveats

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

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.