Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01285362 |
| Other study ID # |
AAAF0695 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 2013 |
| Est. completion date |
September 2014 |
Study information
| Verified date |
May 2022 |
| Source |
Columbia University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Over the past 30 years, the prevalence of childhood obesity in the United States has tripled
from 5% to 15%. Major consequences of obesity include insulin resistance, type- 2 diabetes,
cardiovascular disease and nonalcoholic fatty liver disease (NAFLD). The liver pathology
encompasses a range from isolated fatty liver to advanced fibrosis, cirrhosis and end-stage
liver disease. 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. Medical treatment directed specifically at the
liver disease has only recently been investigated and approved in patients with NAFLD. The
beneficial effects of fish oil are attributed to its high concentrations of n - 3 fatty
acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are major regulators
of pathways that participate in decreased production and break down of triglycerides and
fatty acids in the liver. The investigators hypothesize that children with obesity related
NAFLD will normalize elevated liver enzymes, plasma lipid levels, and attenuate insulin
resistance with supplements of n-3 fatty acids. 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.
Description:
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
eicosanoid 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.
The investigators 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 - GlaxoSmithKline (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, Gamma-glutamyl transferase
(GGT), plasma phospholipids, plasma lipids, insulin levels and estimation of HOMA-R.
