Genetics of Fatty Liver Disease in Children

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01966627
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 381
• Location: 1
• Duration (Months): 72
• Patients Per Site Per Month: 5.3

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Non Alcoholic Fatty Liver Disease	Other: ogtt; Other: genotyping; Other: abdominal and liver magnetic resonance imaging; Other: stool sample; Other: liver biopsy

Detailed 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.

Study Design

• Study Type: Observational
• Actual Enrollment: 381 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Genetics of Fatty Liver Disease in Childhood Obesity.
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Jul 1, 2017
• Actual Study Completion Date: Jul 1, 2017

Arms and Interventions

Arm

Intervention/Treatment

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.

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

Outcome Measures

Primary Outcome Measures

1. gene expression [Baseline]

   gene mutation allele variation identification measure via gene extraction

Secondary Outcome Measures

1. hepatic fat content [2 years]

   Abdominal MRI to measure liver fat and subcutaneous and visceral fat ratio done at baseline and 2 year follow up

2. glucose tolerance [2 years]

   glucose tolerance status measured by 3 hour oral glucose tolerance test done at baseline and 2 year follow up

Other Outcome Measures

1. DNA gene sequencing of intestinal bacteria's [2 years]

   Measure microbiota diversity via stool samples to understand variance of triglycerides accumulation in liver

2. Use liver biopsy specimen to assess differences in gene expression, as well as inflammation. [As indicated by Pediatric Hepatolgist]

   liver biopsy tissue obtained when subject is scheduled for pre-ordered biopsy by hepatologist

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University	New Haven	Connecticut	United States	06510

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Sonia Caprio, M.D., Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.

• Responsible Party: Sonia Caprio, Principal Investigator, Yale University
• ClinicalTrials.gov Identifier: NCT01966627
• Other Study ID Numbers: 1104008388; R01HD040787
• First Posted: Oct 21, 2013
• Last Update Posted: Dec 8, 2017
• Last Verified: Dec 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sonia Caprio, Principal Investigator, Yale University: non alcoholic fatty liver; childhood obesity; genetic variants
• Additional relevant MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Extracts

Study Results

No Results Posted as of Dec 8, 2017