Genetics of Fatty Liver Disease in Children

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Yale University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sonia Caprio, Yale University
ClinicalTrials.gov Identifier:
NCT01966627
First received: July 15, 2013
Last updated: June 16, 2014
Last verified: June 2014
  Purpose

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 Intervention
Non Alcoholic Fatty Liver Disease
Other: ogtt
Other: genotyping
Other: abdominal and liver magnetic resonance imaging
Other: stool sample
Other: liver biopsy

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Genetics of Fatty Liver Disease in Childhood Obesity.

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • gene expression [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    gene mutation allele variation identification measure via gene extraction


Secondary Outcome Measures:
  • hepatic fat content [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Abdominal MRI to measure liver fat and subcutaneous and visceral fat ratio done at baseline and 2 year follow up

  • glucose tolerance [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    glucose tolerance status measured by 3 hour oral glucose tolerance test done at baseline and 2 year follow up


Other Outcome Measures:
  • DNA gene sequencing of intestinal bacteria's [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Measure microbiota diversity via stool samples to understand variance of triglycerides accumulation in liver

  • Use liver biopsy specimen to assess differences in gene expression, as well as inflammation. [ Time Frame: As indicated by Pediatric Hepatolgist ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Serum


Estimated Enrollment: 1000
Study Start Date: July 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   7 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01966627

Contacts
Contact: Melissa Shaw, B.A. 203-785-6459 melissa.m.shaw@yale.edu

Locations
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06510
Contact: Bridget Pierpont, M.A.    203-785-2942      
Principal Investigator: Sonia Caprio, M.D.         
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Sonia Caprio, M.D. Yale University
  More Information

Publications:
Responsible Party: Sonia Caprio, Principal Investigator, Yale University
ClinicalTrials.gov Identifier: NCT01966627     History of Changes
Other Study ID Numbers: 1104008388, R01HD040787
Study First Received: July 15, 2013
Last Updated: June 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
non alcoholic fatty liver
childhood obesity
genetic variants

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases
Liver Extracts
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014