Polyunsaturated Fatty Acids (PUFA) in Diabetic Fatty Liver

NCT00323414 | Completed Phase 2 Results DMC

• 2 other identifiers: DK61732U01DK061732
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

Non-alcoholic steatohepatitis (NASH), the most severe form of liver injury in the spectrum of non-alcoholic fatty liver disease (NAFLD), has emerged as the major cause of chronic liver disease in developed countries. Among adults in the United States, the prevalence is between 5.7% and 17%. These rates are expected to increase concurrent with the epidemics of obesity and type 2 diabetes mellitus, which are the major risk factors for NAFLD and NASH. In addition to its high prevalence, NASH is also a progressive fibrotic disease that advances to cirrhosis and liver related death in 20% and 12% of patients, respectively. Among NASH patients with cirrhosis, 40% have liver related death. Diabetics are particularly prone to experience these poor outcomes. No therapy has been proven effective for patients with NASH. The purpose of this study is to find out whether treatment with polyunsaturated fatty acids (eicosapentaenoic acid \[EPA\] combined with docosahexaenoic acid \[DHA\] called Opti-EPA) improves NASH compared to treatment with placebo pills. The placebo pills will contain corn oil and will be contained in a capsule, but have no medical effect on the body. The investigators will determine improvement in NASH from microscopic changes in the subject's liver tissue during 48 weeks of treatment. This means that the subject will need to have a liver biopsy before and after the treatment. Omega-3 fatty acids are a form of polyunsaturated fats, one of the four basic types of fat that the body gets from food. (Cholesterol, saturated fat, and monounsaturated fat are the others.) One's body does not make this type of fat; it comes from food sources. These fats are found in foods like cold water fish (tuna, salmon, and mackerel), and vegetable products like flaxseed oil and walnuts. Research shows that polyunsaturated fats are good for people. Studies have shown that it is good for heart health by playing a role in keeping blood cholesterol levels low, keeping irregular heart rhythms stable, and reducing blood pressure. The drug being studied, Opti-EPA, is a nutritional supplement. They do not have to be reviewed by the Food and Drug Administration (FDA) like medicines do. Opti-EPA is considered experimental in this study. This means that the United States Food and Drug Administration (FDA) has not approved it for use in people with nonalcoholic fatty liver disease.

Conditions

Fatty Liver

Keywords

PUFA; NASH; Fatty Liver; Insulin resistance; Metabolic syndrome; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Improvement of >= 2 Points in NAFLD Activity Score (NAS)

  The non-alcoholic fatty liver disease (NAFLD) activity score (NAS) is a score based on the liver biopsy. It represents the sum of scores for steatosis, lobular inflammation, and ballooning, and ranges from 0-8, with high scores indicating more activity.

  48 weeks

Secondary Outcomes (5)

• Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) Values

  48 weeks

• Aspartate Amino Transferase (AST) Levels

  48 weeks

• Alanine Amino Transferase (ALT) Levels

  48 weeks

• Blood Glucose Levels

  48 weeks

• HbA1C Levels

  48 weeks

Study Arms (2)

Polyunsaturated fatty acid (Opti-EPA)

ACTIVE COMPARATOR

Polyunsaturated fatty acid will consist of purified EPA:DHA (360 mg EPA and 240 mg DHA) 6 gelcaps-3 capsules by mouth 2x per day x 48 weeks

Drug: Polyunsaturated fatty acid (Opti-EPA)

Placebo

PLACEBO COMPARATOR

Gelcaps containing corn oil as placebo 6 capsules 3 capsules by mouth 2 x per day for 48 weeks

Drug: Placebo

Interventions

Polyunsaturated fatty acid (Opti-EPA) DRUG

Active experimental arm to patients with diabetes mellitus and non alcoholic steatohepatitis: Eicosapentaenoic acid (EPA):Docosahexaenoic acid (DHA)\[360 mg EPA and 240 DHA in each capsule\] 6 capsules-3 capsules by mouth 2 x per day x 48 weeks

Also known as: Fish oil

Polyunsaturated fatty acid (Opti-EPA)

Placebo DRUG

Placebo gelcaps containing corn oil identical to the PUFA gelcaps 6 capsules-3 capsules by mouth 2x per day x 48 weeks

Also known as: Corn oil

Placebo

Eligibility Criteria

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

You may qualify if:

• Adult patients (age \>18 years)
• Have type 2 diabetes mellitus with good control of blood sugar (hemoglobin A1c \[HbA1c\] \<7.5%) and will have been on a stable regimen of anti-diabetic agents for more than 4 months.

You may not qualify if:

• Cirrhosis of the liver
• End stage target organ damage in diabetes mellitus: advanced renal failure (serum creatinine \> 2.0 mg/dl) with or without dialysis, severe neuropathy, or advanced peripheral vascular disease.
• Any organ dysfunction with anticipated life expectancy of less than 2 years
• Co-existent etiologies for liver disease
• Significant alcohol consumption, defined as more than 30 g per day in men and more than 20 g per day in women.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (2)

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Related Publications (2)

• Younossi ZM, Gramlich T, Matteoni CA, Boparai N, McCullough AJ. Nonalcoholic fatty liver disease in patients with type 2 diabetes. Clin Gastroenterol Hepatol. 2004 Mar;2(3):262-5. doi: 10.1016/s1542-3565(04)00014-x.

  PMID: 15017611 BACKGROUND

• Dasarathy S, Dasarathy J, Khiyami A, Yerian L, Hawkins C, Sargent R, McCullough AJ. Double-blind randomized placebo-controlled clinical trial of omega 3 fatty acids for the treatment of diabetic patients with nonalcoholic steatohepatitis. J Clin Gastroenterol. 2015 Feb;49(2):137-44. doi: 10.1097/MCG.0000000000000099.

  PMID: 24583757 DERIVED

MeSH Terms

Conditions

Fatty Liver; Insulin Resistance; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2

Interventions

Fatty Acids, Unsaturated; Fish Oils; Corn Oil

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Fatty Acids; Lipids; Oils; Dietary Fats, Unsaturated; Dietary Fats; Fats; Fats, Unsaturated; Plant Oils; Plant Preparations; Biological Products; Complex Mixtures; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Results Point of Contact

• Title: Srinivasan Dasarathy MD
• Organization: Cleveland Clinic Foundation

dasaras@ccf.org

216-444-2766

Study Officials

• Arthur J. McCullough, M.D.

  MetroHealth Medical Center

  PRINCIPAL INVESTIGATOR

• Srinivasan Dasarathy, M.D.

  The Cleveland Clinic

  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: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2006
• First Posted: May 9, 2006
• Study Start: April 1, 2006
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: February 23, 2018
• Results First Posted: February 23, 2018

Record last verified: 2017-10

Locations

US (2)