Clinical trial NCT01966627: Genetics of Fatty Liver Disease in Children
Official title: Genetics of Fatty Liver Disease in Childhood Obesity.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Non Alcoholic Fatty Liver Disease
Keywords: non alcoholic fatty liver
childhood obesity
genetic variants
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2013-10-21
Enrollment: 381
Sex: ALL
Minimum age (years): 7
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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 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.

Primary outcomes:
measure: gene expression
timeFrame: Baseline
Secondary outcomes:
measure: hepatic fat content
timeFrame: 2 years
measure: glucose tolerance
timeFrame: 2 years
Other outcomes:
measure: DNA gene sequencing of intestinal bacteria's
timeFrame: 2 years
measure: Use liver biopsy specimen to assess differences in gene expression, as well as inflammation.
timeFrame: As indicated by Pediatric Hepatolgist
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
Study officials:
affiliation: Yale University
name: Sonia Caprio, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.