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Genetics of Fatty Liver Disease in Children

This study is currently recruiting participants.
Verified April 2017 by Sonia Caprio, Yale University
Sponsor:
ClinicalTrials.gov Identifier:
NCT01966627
First Posted: October 21, 2013
Last Update Posted: April 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Sonia Caprio, Yale University
  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 Sonia Caprio, Yale University:

Primary Outcome Measures:
  • gene expression [ Time Frame: Baseline ]
    gene mutation allele variation identification measure via gene extraction


Secondary Outcome Measures:
  • hepatic fat content [ Time Frame: 2 years ]
    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 ]
    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 ]
    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 ]
    liver biopsy tissue obtained when subject is scheduled for pre-ordered biopsy by hepatologist


Biospecimen Retention:   Samples With DNA
Serum

Estimated Enrollment: 1000
Study Start Date: July 2011
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: December 2020 (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

Information from the National Library of Medicine

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Ages Eligible for Study:   7 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01966627


Contacts
Contact: Bridget Pierpont, MA 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
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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 ( U.S. NIH Grant/Contract )
First Submitted: July 15, 2013
First Posted: October 21, 2013
Last Update Posted: April 27, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Liver Extracts
Hematinics