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

NCT00681408 | Completed Phase 2 DMC

• 5 other identifiers: 12442R21AT002901IRB # 12442GCRC: SHC003Grant # 5R21AT2901-2
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-alcoholic Steatohepatitis; Fatty Liver

Keywords

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

Outcome Measures

Primary Outcomes (1)

• The Primary endpoint will be improvement in a composite score of histological injury as measured by the NASH Activity Score (NAS).

  approximately 12 months from enrollment

Secondary Outcomes (4)

• Measurement of anthropometric indices (weight, BMI, waist circumference)

  12 months

• Index of cardiorespiratory fitness determined by exercise tolerance (measured by lactate threshold on an exercise treadmill)

  12 months

• Hepatic fat content measured by magnetic resonance imaging

  12 months

• 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

  12 mos

Study Arms (2)

Omega 3 recipient arm

ACTIVE COMPARATOR

Drug: Omega 3 Fish Oil supplements

Placebo

PLACEBO COMPARATOR

Placebo fish oil

Drug: Placebo

Interventions

Omega 3 Fish Oil supplements DRUG

Subjects in this arm will receive 3 grams daily Omega 3 fish oil supplements

Also known as: Fish Oil capsules

Omega 3 recipient arm

Placebo DRUG

Fish oil placebo pills

Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Virginia: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

University of Virginia School of Medicine

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• 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.

  PMID: 25195547 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fatty Liver

Interventions

Fish Oils

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Oils; Lipids

Study Officials

• Stephen H Caldwell, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 19, 2008
• First Posted: May 21, 2008
• Study Start: March 1, 2007
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: May 29, 2015

Record last verified: 2015-05

Locations

US (1)