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Development of Biomarker for Development of Non-Alcoholic Steatohepatitis (NASH) in Children (NASH)

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ClinicalTrials.gov Identifier: NCT00677183
Recruitment Status : Withdrawn (PI did not receive funding for this PI-initiated study. PI subsequently left the institution.)
First Posted : May 14, 2008
Last Update Posted : August 25, 2015
Information provided by (Responsible Party):
Medical College of Wisconsin

Brief Summary:
The purpose of this study is to document how often specific genotypes known to be associated with adult-onset NASH (Non-Alcoholic Steatohepatitis) occur in a pediatric cohort and investigate whether these genotypes are associated with increased susceptibility to NASH.

Condition or disease
Non-Alcoholic Steatohepatitis

Detailed Description:

NASH is a clinico-pathological entity characterized by the development of histological changes of inflammation and fibrosis in the liver that are nearly identical to those induced by excessive alcohol intake, but in the absence of alcohol abuse. Nonalcoholic steatohepatitis occurs commonly children with additional comorbidities such as obesity and diabetes mellitus. Paralleling the increasing prevalence of obesity and type 2 diabetes in the pediatric population, nonalcoholic fatty liver disease (NAFLD) and especially its more severe histological form NASH, is expected to become one of the most common causes of end-stage liver disease in both children and young adults.

Although no genome wide association studies have been conducted in association with NASH to date, individual candidate gene investigations have identified several genes associated with increase susceptibility to NASH in adults including the microsomal triglyceride transfer protein (MTP) which regulates the incorporation of triglycerides into apolipoprotein B and a key enzyme for the assembly and secretion of VLDL from hepatocytes, the manganese superoxide dismutase (MnSOD) gene which catalyzes the conversion of two molecules of superoxide anion, a highly unstable ROS, into hydrogen peroxide and oxygen more stable ROS, and lastly, phosphatidylethanolamine N-methyltransferase (PEMT) which is required for hepatic secretion of triacylglycerol in very low density lipoproteins (VLDL).

We propose the following aim:

Aim 1: To document the frequency of specific genotypes, previously identified to be associated with adult-onset NASH, in a purely pediatric cohort.

Aim 2: To investigate whether these genotypes are associated with increased susceptibility to NASH and increased occurrence of fibrosis in the cohort of pediatric subjects. Our hypothesis would be:

A significantly higher proportion of the polymorphisms would exist in those subjects with NASH compared to controls.

Aim 3: To investigate the presence of other polymorphisms or other biomarker that are indicative of pediatric NASH. Such that our secondary hypothesis would be:

Specific polymorphisms or biomarkers will be identified that will indicate a higher probability of NASH.

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Study Type : Observational
Actual Enrollment : 0 participants
Observational Model: Family-Based
Time Perspective: Prospective
Official Title: Development of a Biomarker for Development of Non-Alcoholic Steatohepatitis (NASH) in Children
Study Start Date : May 2008
Estimated Primary Completion Date : May 2016
Estimated Study Completion Date : May 2016

Resource links provided by the National Library of Medicine

All children in this cohort will have biopsy-proven NASH.
This cohort will be parents (mother and father when possible) of child subjects with biopsy-proven NASH.

Primary Outcome Measures :
  1. We will compare known frequencies from the Hapmap and specifically compare the proportions for those with NASH in adults to see if there is a difference in the child incidence of NASH. [ Time Frame: three years ]
  2. We will compare the proportions of those with NASH to those without NASH and those with fibrosis compared to those without fibrosis. [ Time Frame: Three years ]

Biospecimen Retention:   Samples With DNA
10mL of blood will be retained from each participant and their parents. 5mL of this blood will undergo DNA extraction and genotyping for several known NASH related genes. The other 5mL of blood will be saved as serum for future analysis.

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
The child subjects will be recruited from the Hepatology Clinic at Children's Hospital of Wisconsin.

Inclusion Criteria:

  • All subjects aged 2-18 with biopsy proven NAFLD and/or NASH undergoing a blood draw and willing to consent to this study will qualify for inclusion in this protocol.

Exclusion Criteria:

  • other causes of chronic liver disease or other chronic diseases, specifically autoimmune disorders, immunodeficiencies, or individuals with congenital/genetic disorders
  • chronic viral hepatitis, Wilson's disease, or alpha -1- antitrypsin deficiency
  • acute life threatening illness or conditions

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00677183

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United States, Wisconsin
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Medical College of Wisconsin
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Principal Investigator: Vincent F Biank, MD Medical College of Wisconsin
Benjamini, Y. and Hochberg, Y. 1995. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. Royal Stat. Soc. B (57): 289-300.
Breiman L, Friedman JH, Olshen RA, Stone CJ. Classification and Regression Trees. Classification and Regression Trees. 1984.

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Responsible Party: Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT00677183    
Other Study ID Numbers: CHW 08/36
GC 618
First Posted: May 14, 2008    Key Record Dates
Last Update Posted: August 25, 2015
Last Verified: August 2015
Keywords provided by Medical College of Wisconsin:
Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases