Omega 3 Fish Oil Supplements vs. Placebo for Patients With Non-alcoholic Steatohepatitis (NASH)

• ClinicalTrials.gov Identifier: NCT00681408
• Recruitment Status: Completed
• First Posted: May 21, 2008
• Last Update Posted: May 29, 2015
• Sponsor: University of Virginia
• Collaborator: National Center for Complementary and Integrative Health (NCCIH)
• Information provided by (Responsible Party): Stephen Caldwell, MD, University of Virginia

Study Description

Brief Summary:

Nonalcoholic steatohepatitis (NASH) occurs in 2-3% of the US population and carries a 15-20% chance of progression to cirrhosis. It is closely associated with obesity, hyperlipidemia and insulin resistance. Therapy usually includes recommendations to increase exercise and to begin weight reducing diets but these goals are variably achieved and their relative effects in conjunction with pharmacological intervention have not been well defined. Moreover, these lifestyle changes can confound results of treatment trials if not quantified through conditioning testing and measures of body fat. Polyunsaturated fatty acids, especially formulation rich in omega-3, are widely accepted and endorsed in the medical community for their beneficial effects on hyperlipidemia and coronary disease risk reduction. Recent data suggests that omega-3 fatty acids ameliorate hepatic steatosis in humans and in animal models of NASH by reducing hepatic fat content. We hypothesize that a one year course of omega-3 fatty acid (3gm/day) will produce improvement in NASH histological injury independent of changes in weight (BMI) or degree of conditioning measured by the lactate threshold. The effects of the supplement will be compared to a placebo group and controlled for these lifestyle changes.

Condition or disease	Intervention/treatment	Phase
Non-alcoholic Steatohepatitis; Fatty Liver	Drug: Omega 3 Fish Oil supplements; Drug: Placebo	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Omega 3 Fish Oil Supplements vs. Placebo for Patients With Non-alcoholic Steatohepatitis (NASH)
• Study Start Date: March 2007
• Actual Primary Completion Date: August 2010
• Actual Study Completion Date: August 2010

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Omega 3 recipient arm	Drug: Omega 3 Fish Oil supplements; Subjects in this arm will receive 3 grams daily Omega 3 fish oil supplements; Other Name: Fish Oil capsules
Placebo Comparator: Placebo; Placebo fish oil	Drug: Placebo; Fish oil placebo pills

Outcome Measures

Primary Outcome Measures :

1. The Primary endpoint will be improvement in a composite score of histological injury as measured by the NASH Activity Score (NAS). [ Time Frame: approximately 12 months from enrollment ]

Secondary Outcome Measures :

1. Measurement of anthropometric indices (weight, BMI, waist circumference) [ Time Frame: 12 months ]
2. Index of cardiorespiratory fitness determined by exercise tolerance (measured by lactate threshold on an exercise treadmill) [ Time Frame: 12 months ]
3. Hepatic fat content measured by magnetic resonance imaging [ Time Frame: 12 months ]
4. Changes in fasting plasma lipids, red cell fatty acid content, changes in anti-hyperlipidemia requirements, insulin sensitivity, and markers of inflammation including tumor necrosis factor and C-reactive protein [ Time Frame: 12 mos ]

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. NASH with NAS (NASH Activity Score) of >4 evident on a biopsy performed within 6 months of enrollment.
2. Age 21 years or older.
3. BMI 25 or greater.
4. Ability to provide informed consent.

Exclusion Criteria:

1. Cirrhosis evident clinically or on biopsy.
2. Secondary forms of NASH such as that seen with bariatric surgery or medication induced from such medications as methotrexate, amiodarone, tamoxifen, corticosteroids.
3. Current or past history of diabetes or hyperlipidemia requiring specific drug therapy (see below).
4. Current use of a weight loss medicine, such as a 'fat-burner' or similar agent
5. Alcohol consumption > 30 g/day, currently or for more than 3 consecutive months within 5 years.
6. Other liver disease (hepatitis C,B, Wilson's, autoimmune, ct-1-antitrypsin and hemochromatosis or HIV
7. Pregnancy or unwillingness to use an effective form of birth control for women of child bearing years.
8. Renal insufficiency (creatinine > 2), symptomatic coronary, peripheral or neurovascular disease, symptomatic heart failure or advanced respiratory disease requiring oxygen therapy.
9. Inability to provide informed consent.
10. Any condition in the opinion of the primary investigator that would contraindicate the patient's participation.

Contacts and Locations

Locations

United States, Virginia

University of Virginia School of Medicine

Charlottesville, Virginia, United States, 22908

Sponsors and Collaborators

University of Virginia

National Center for Complementary and Integrative Health (NCCIH)

Investigators

• Principal Investigator: Stephen H Caldwell, MD; University of Virginia

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Argo CK, Patrie JT, Lackner C, Henry TD, de Lange EE, Weltman AL, Shah NL, Al-Osaimi AM, Pramoonjago P, Jayakumar S, Binder LP, Simmons-Egolf WD, Burks SG, Bao Y, Taylor AG, Rodriguez J, Caldwell SH. Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial. J Hepatol. 2015 Jan;62(1):190-7. doi: 10.1016/j.jhep.2014.08.036. Epub 2014 Sep 6.

• Responsible Party: Stephen Caldwell, MD, Professor, Department of Gastroenterology, University of Virginia
• ClinicalTrials.gov Identifier: NCT00681408
• Other Study ID Numbers: 12442; R21AT002901 ( U.S. NIH Grant/Contract ); IRB # 12442; GCRC: SHC003; Grant # 5R21AT2901-2
• First Posted: May 21, 2008
• Last Update Posted: May 29, 2015
• Last Verified: May 2015

Keywords provided by Stephen Caldwell, MD, University of Virginia:

Steatohepatitis; NASH; NAFLD; omega 3 fatty acids; Exercise conditioning

Additional relevant MeSH terms:

Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Diseases; Digestive System Diseases