Polyunsaturated Fatty Acids (PUFA) in Diabetic Fatty Liver
Condition: Fatty Liver
MeSH terms: Fatty Liver
Intervention: Polyunsaturated fatty acid (Opti-EPA); Placebo
Intervention description: 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; Placebo gelcaps containing corn oil identical to the PUFA gelcaps 6 capsules-3 capsules by mouth 2x per day x 48 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PUFA; NASH; Fatty Liver; Insulin resistance; Metabolic syndrome; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Type 2 Diabetes Mellitus

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

          -  NASH established on liver biopsy done within 6 months prior to inclusion in the study
             as determined by established histologic criteria

        Exclusion Criteria:

          -  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.