Genetics of Fatty Liver Disease in Children

Non Alcoholic Fatty Liver Disease Clinical Trial

Official title:

Genetics of Fatty Liver Disease in Childhood Obesity.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01966627
• Other study ID #: 1104008388
• Secondary ID: R01HD040787
• Status: Completed
• Phase: N/A
• First received: July 15, 2013
• Last updated: December 6, 2017
• Start date: July 2011
• Est. completion date: July 2017

Study information

• Verified date: December 2017
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 381
• Est. completion date: July 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non Alcoholic Fatty Liver Disease
• Non-alcoholic Fatty Liver Disease

Intervention

Other:
• ogtt
oral glucose tolerance test
• genotyping
genotyping to look for risk alleles
• abdominal and liver magnetic resonance imaging
magnetic resonance imaging scan of abdomen and liver - abdominal and liver mri
• stool sample
stool sample taken to investigate metabolites
• liver biopsy
liver biopsy to examine for cellular change and steatosis

Locations

Country	Name	City	State
United States	Yale University	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. Epub 2006 Aug 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	DNA gene sequencing of intestinal bacteria's	Measure microbiota diversity via stool samples to understand variance of triglycerides accumulation in liver	2 years
Other	Use liver biopsy specimen to assess differences in gene expression, as well as inflammation.	liver biopsy tissue obtained when subject is scheduled for pre-ordered biopsy by hepatologist	As indicated by Pediatric Hepatolgist
Primary	gene expression	gene mutation allele variation identification measure via gene extraction	Baseline
Secondary	hepatic fat content	Abdominal MRI to measure liver fat and subcutaneous and visceral fat ratio done at baseline and 2 year follow up	2 years
Secondary	glucose tolerance	glucose tolerance status measured by 3 hour oral glucose tolerance test done at baseline and 2 year follow up	2 years