Genetics of Fatty Liver Disease in Children

NCT01966627 | Completed

• 2 other identifiers: 1104008388R01HD040787
• Study Type: observational
• Target: 381
• Locations: 1 country
• Sites: 1

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.

Conditions

Non Alcoholic Fatty Liver Disease

Keywords

non alcoholic fatty liver; childhood obesity; genetic variants

Outcome Measures

Primary Outcomes (1)

• gene expression

  gene mutation allele variation identification measure via gene extraction

  Baseline

Secondary Outcomes (2)

• hepatic fat content

  2 years

• glucose tolerance

  2 years

Other Outcomes (2)

• DNA gene sequencing of intestinal bacteria's

  2 years

• Use liver biopsy specimen to assess differences in gene expression, as well as inflammation.

  As indicated by Pediatric Hepatolgist

Study Arms (1)

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; Other: genotyping; Other: abdominal and liver magnetic resonance imaging; Other: stool sample; Other: liver biopsy

Interventions

ogtt OTHER

oral glucose tolerance test

Pediatric NAFLD Cohort

genotyping OTHER

genotyping to look for risk alleles

Pediatric NAFLD Cohort

abdominal and liver magnetic resonance imaging OTHER

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

Pediatric NAFLD Cohort

stool sample OTHER

stool sample taken to investigate metabolites

Pediatric NAFLD Cohort

liver biopsy OTHER

liver biopsy to examine for cellular change and steatosis

Pediatric NAFLD Cohort

Eligibility Criteria

• Age: 7 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The majority of the research subjects will be recruited from the Yale Pediatric Obesity Clinic and the Endocrine Clinic.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

Location

Related Publications (2)

• 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.

  PMID: 16912127 BACKGROUND

• 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.

  PMID: 29665034 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Subjects with DNA samples collected

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Pediatric Obesity

Interventions

Glucose Tolerance Test; Genotype

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques; Genetic Phenomena

Study Officials

• Sonia Caprio, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 15, 2013
• First Posted: October 21, 2013
• Study Start: July 1, 2011
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: December 8, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)