Polyunsaturated Fatty Acids (PUFA) in Diabetic Fatty Liver
| Status: | Completed |
|---|---|
| Conditions: | Gastrointestinal, Diabetes |
| Therapuetic Areas: | Endocrinology, Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/24/2018 |
| Start Date: | April 2006 |
| End Date: | December 2011 |
Randomized Controlled Trial of Omega-3 Fatty Acids in the Treatment of Non-Alcoholic Steatohepatitis in Patients With Type 2 Diabetes Mellitus
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.
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.
Although there is no proven effective treatment of NASH, dietary supplementation with long
chain omega-3 polyunsaturated fatty acids (PUFA's) may be beneficial. This suggestion is
based on three previously reported observations: first, patients with NASH consume less PUFAs
and more saturated fats than subjects without NASH. Second, PUFAs are beneficial in patients
with hypertension and hypertriglyceridemia. Third, PUFAs decrease lipid peroxidation and
ameliorate hepatic steatosis in animal models of NAFLD.
We therefore hypothesize that the administration of these PUFAs, eicosapentaenoic acid (EPA)
and docosahexaenoic acid (DHA) will reduce hepatic fat content, inflammation and hepatic
injury in patients with type 2 diabetes mellitus who have NASH.
Aims
To determine in patients with type 2 diabetes mellitus who have NASH if dietary
supplementation with purified omega-3 fatty acids (EPA and DHA) will:
1. Decrease the histologic severity of NASH.
2. Alter the expression of genes important in the pathways of hepatic lipid synthesis and
oxidation.
Study design:
Patients who meet the inclusion criteria will be randomized to receive omega-3 fatty acids or
placebo. Stratified randomization will be done based on the NASH Clinical Research Network
pathology score of 5.
chain omega-3 polyunsaturated fatty acids (PUFA's) may be beneficial. This suggestion is
based on three previously reported observations: first, patients with NASH consume less PUFAs
and more saturated fats than subjects without NASH. Second, PUFAs are beneficial in patients
with hypertension and hypertriglyceridemia. Third, PUFAs decrease lipid peroxidation and
ameliorate hepatic steatosis in animal models of NAFLD.
We therefore hypothesize that the administration of these PUFAs, eicosapentaenoic acid (EPA)
and docosahexaenoic acid (DHA) will reduce hepatic fat content, inflammation and hepatic
injury in patients with type 2 diabetes mellitus who have NASH.
Aims
To determine in patients with type 2 diabetes mellitus who have NASH if dietary
supplementation with purified omega-3 fatty acids (EPA and DHA) will:
1. Decrease the histologic severity of NASH.
2. Alter the expression of genes important in the pathways of hepatic lipid synthesis and
oxidation.
Study design:
Patients who meet the inclusion criteria will be randomized to receive omega-3 fatty acids or
placebo. Stratified randomization will be done based on the NASH Clinical Research Network
pathology score of 5.
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.
We found this trial at
2
sites
Cleveland Clinic Foundation The Cleveland Clinic (formally known as The Cleveland Clinic Foundation) is a...
Click here to add this to my saved trials
MetroHealth Med Ctr The MetroHealth System is one of the largest, most comprehensive health care...
Click here to add this to my saved trials