Genetics of Fatty Liver Disease in Children

NCT ID: NCT01966627

Last Updated: 2017-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

381 participants

Study Classification

OBSERVATIONAL

Study Start Date

2011-07-31

Study Completion Date

2017-07-31

Brief Summary

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This is a study to investigate genetic predisposition to hepatic steatosis and the expression of gluconeogenic and lipogenic genes in livers of obese children and adolescents.

Hypothesis 1: Common variants recently associated with variation in plasma TG levels identified in Genome Wide Association Studies (GWAS) (such as GCKR, PNPLA3) can affect accumulation of fat and subsequent development of Non Alcoholic Fatty Liver Disease (NAFLD). Gene variants act in additive or synergistic manner with progressive liver fat accumulation per additional risk allele.

Hypothesis 2: With increase in hepatic fat content NASH and fibrosis will increase. Furthermore, expression of lipogenic markers (SREBP1c) will increase.

Detailed Description

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To establish a cohort of obese youths to prospectively analyze potential factors (genetic and nutritional factors) that might affect the expression and progression of NAFLD. This study will determine genetic markers and their ability to convey susceptibility to NAFLD in obese children and adolescents. Furthermore, potential mechanisms that might contribute to the accumulation of hepatic Triglyceride (TG) accumulation will be, for the first time, assessed by genotyping. Additionally, we will examine the presence of intestinal microbiome in the development of fatty liver through stool collection.

Conditions

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Non Alcoholic Fatty Liver Disease

Keywords

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non alcoholic fatty liver childhood obesity genetic variants

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Pediatric NAFLD Cohort

Overweight and obese children and adolescents at risk for non alcoholic fatty liver disease will undergo oral glucose tolerance testing (ogtt), genotyping, abdominal and liver magnetic resonance imaging (mri), and will provide a stool sample at baseline and at 2 year follow up. A small subset will undergo liver biopsy to test for hepatic steatosis and nonalcoholic steatohepatitis.

ogtt

Intervention Type OTHER

oral glucose tolerance test

genotyping

Intervention Type OTHER

genotyping to look for risk alleles

abdominal and liver magnetic resonance imaging

Intervention Type OTHER

magnetic resonance imaging scan of abdomen and liver - abdominal and liver mri

stool sample

Intervention Type OTHER

stool sample taken to investigate metabolites

liver biopsy

Intervention Type OTHER

liver biopsy to examine for cellular change and steatosis

Interventions

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ogtt

oral glucose tolerance test

Intervention Type OTHER

genotyping

genotyping to look for risk alleles

Intervention Type OTHER

abdominal and liver magnetic resonance imaging

magnetic resonance imaging scan of abdomen and liver - abdominal and liver mri

Intervention Type OTHER

stool sample

stool sample taken to investigate metabolites

Intervention Type OTHER

liver biopsy

liver biopsy to examine for cellular change and steatosis

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* between 7 and 18 years of age,
* overweight or obese with a BMI greater than the 85th percentile for age and gender, and
* be otherwise healthy.

Exclusion Criteria

* the use of any medication that alters liver function, blood pressure, glucose or lipid metabolism and
* no use of any antipsychotic medication
* Youth on chronic anti-inflammatory medications or who consume alcohol are also excluded.
Minimum Eligible Age

7 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

Yale University

OTHER

Sponsor Role lead

Responsible Party

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Sonia Caprio

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sonia Caprio, M.D.

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

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Yale University

New Haven, Connecticut, United States

Site Status

Countries

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United States

References

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Burgert TS, Taksali SE, Dziura J, Goodman TR, Yeckel CW, Papademetris X, Constable RT, Weiss R, Tamborlane WV, Savoye M, Seyal AA, Caprio S. Alanine aminotransferase levels and fatty liver in childhood obesity: associations with insulin resistance, adiponectin, and visceral fat. J Clin Endocrinol Metab. 2006 Nov;91(11):4287-94. doi: 10.1210/jc.2006-1010. Epub 2006 Aug 15.

Reference Type BACKGROUND
PMID: 16912127 (View on PubMed)

Trico D, Caprio S, Rosaria Umano G, Pierpont B, Nouws J, Galderisi A, Kim G, Mata MM, Santoro N. Metabolic Features of Nonalcoholic Fatty Liver (NAFL) in Obese Adolescents: Findings From a Multiethnic Cohort. Hepatology. 2018 Oct;68(4):1376-1390. doi: 10.1002/hep.30035.

Reference Type DERIVED
PMID: 29665034 (View on PubMed)

Other Identifiers

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R01HD040787

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1104008388

Identifier Type: -

Identifier Source: org_study_id