Fish Oil and Nonalcoholic Fatty Liver Disease (NAFLD) Study
キーワード
概要
説明
Scientific Abstract:
Over the past 30 years, the prevalence of childhood obesity in the United States has tripled from 5% to 15%. Overweight is defined as a body mass index (BMI) above the 95%centile for age and gender. The recent estimates of obesity prevalence based on the National Health and Nutrition Examination Study (NHANES) 1999-2000 suggest that 15.3% to 15.5% of 6-19 year old children have a BMI above the 95% centile for age. Major consequences of obesity include insulin resistance, type 2 diabetes mellitus, cardiovascular disease and nonalcoholic fatty liver disease (NAFLD). NAFLD represents a spectrum of conditions characterized by macrovesicular hepatic steatosis. The liver pathology encompasses a range from isolated fatty liver to steatohepatitis, advanced fibrosis, cirrhosis and end-stage liver disease. Nonalcoholic steatohepatitis (NASH) may progress to cirrhosis even in children. Weight loss, particularly if gradual, may lead to improvement in liver histology. Unfortunately, few patients in the pediatric population are willing to follow these recommendations and achieve weight loss. Pharmacological therapy directed specifically at the liver disease has only recently been investigated in patients with NAFLD. Most of these studies have been uncontrolled pilot studies, lasting one year or less and have produced equivocal results. Thus, there is currently no effective treatment for this disorder. The beneficial effects of fish oil are attributed to its high concentrations of n - 3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Long-chain polyunsaturated n-3 FA (LCPUFA) are major regulators of molecular pathways altering many areas of cellular and organ function, metabolism and gene expression, and are active in reducing inflammation through the eicasanoid pathway. N-3 LCPUFA are well established negative regulators of hepatic lipogenesis. Recently it has been shown that the suppressive effects of n-3 LCPUFA on lipogenic enzymes are mediated by the reduction of mature SREBP-1c protein in the liver, a key transcription factor that activates transcription of genes involved in fatty acid synthesis. It is also well established today that the n-3 LCPUFA act as PPAR-alpha and gamma modulators, important in triglyceride (TG) and fatty acid catabolism. N-3 LCPUFA produce a dramatic increase in the size and number of hepatic peroxisomes and increase the capacity of the hepatocyte to metabolize fatty acids by inducing peroxisomal beta-oxidation enzymes, such as acyl CoA oxidase . We hypothesize that children with obesity related NAFLD will normalize elevated liver enzymes, plasma lipid levels, and attenuate insulin resistance with supplements of n-3 LCPUFA. If this hypothesis is proven true, then fish oil could be used to treat NAFLD and to prevent the deterioration of fatty liver into end-stage liver disease.
We will study 20 patients with NAFLD and hypertriglyceridemia, age 12y and above. Excluded from the study will be those with evidence of chronic infectious hepatitis, metabolic liver disease, autoimmune and chronic cholestatic liver diseases, insulin dependent diabetes and those with history of alcohol consumption, or exposure to drugs or hepatotoxins. Those qualifying for this study will be age 12 and above obese individuals (BMI > 95% for age), who have hyperlipidemia, but will have normal fasting glucose levels. For inclusion all will have elevation of serum aminotransferases to at least 1.5 times the upper limit of normal for a minimum of 3 months and evidence of fatty liver by abdominal ultrasound and liver biopsy. Patients will be randomized to placebo dummy capsules (controls) or n-3 LCPUFA supplements (Lovaza - GSK Pharmaceuticals, provided free of charge) at a dose of 4gr/day. They will be followed up at 3 and 6 months; monitoring height, weight, BMI, liver enzyme levels (ALT, AST, ALP), bilirubin total and direct, GGT, plasma phospholipids, plasma lipids, insulin levels and estimation of HOMA-R.
日付
最終確認済み: | 02/28/2015 |
最初に提出された: | 01/25/2011 |
提出された推定登録数: | 01/26/2011 |
最初の投稿: | 01/27/2011 |
最終更新が送信されました: | 03/04/2015 |
最終更新日: | 03/08/2015 |
実際の研究開始日: | 02/28/2013 |
一次完了予定日: | 08/31/2014 |
研究完了予定日: | 08/31/2014 |
状態または病気
介入/治療
Drug: Fish Oil Supplementation (Group A)
Drug: Placebo Supplementation (Group B)
段階
アームグループ
腕 | 介入/治療 |
---|---|
Active Comparator: Fish Oil Supplementation (Group A) Group A will receive fish oil capsules, containing n3-Fatty Acids, at a dose of 4g/day. Each 1g capsule will contain 465mg of EPA and 375 mg of DHA. | Drug: Fish Oil Supplementation (Group A) Group A will receive fish oil capsules, containing n3-Fatty Acids, at a dose of 4g/day. Each 1g capsule will contain 465mg of EPA and 375 mg of DHA. |
Placebo Comparator: Placebo Supplementation (Group B) Group B will receive corn oil in the capsules at the same dose as Group A. The corn oil capsules will appear identical in size and color to the fish oil capsules. | Drug: Placebo Supplementation (Group B) Group B will receive corn oil in the capsules at the same dose as Group A. The corn oil capsules will appear identical in size and color to the fish oil capsules. |
適格基準
研究の対象となる年齢 | 12 Years に 12 Years |
研究に適格な性別 | All |
健康なボランティアを受け入れる | はい |
基準 | Inclusion Criteria: - Body Mass Index (BMI i.e. wt(Kg)/ht(m)2) above the 95th % as defined by the NHANES tables. - Elevated liver enzymes (ALT and/or AST) to at least 1.5 times the upper limit on at least 2 examinations, (ALT, the upper limit of normal values in our laboratory is 41 U/L; AST, upper limit of normal values in our laboratory is 38 U/L). - Subjects must demonstrate ability to swallow capsules. Exclusion Criteria: - Overt Diabetes - Viral or autoimmune hepatitis, Wilson's disease, Alpha-1 antitrypsin deficiency, hemochromatosis or any other form of chronic liver disease not related to NAFLD - Exposure to drugs or hepatotoxins less than 14 days prior to recruitment - Alcohol consumption > 20 grams/day - Evidence of cirrhosis on liver biopsy. |
結果
主な結果の測定
1. Prevalence of normalized liver enzyme levels [Up to 12 months from entry into the study]
二次的な結果の測定
1. Prevalence of insulin resistance attenuated [Up to 12 months from entry into the study]