We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Hepatic De Novo Lipogenesis (DNL)in the Pathogenesis of Hepatic Steatosis in Obese Youth (DNL)

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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01725035
Recruitment Status : Completed
First Posted : November 12, 2012
Last Update Posted : April 7, 2016
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:

Nonalcoholic Fatty Liver Disease (NAFLD) is becoming the most common cause of liver disease in pediatrics, but little is known about its pathophysiology in children. While studies in obese adults with hepatic steatosis have described an increased hepatic de novo lipogenesis (DNL) depending on the diet, there are no studies exploring the mechanisms by which excess hepatic triglycerides increases in obese youths, thus explaining the accompanying dyslipidemia and the metabolic syndrome. The central hypothesis of this study is that hepatic conversion of carbohydrates to lipid (DNL) is enhanced and associated with accumulation of excess liver fat, dyslipidemia and hepatic insulin resistance in obese youths with hepatic steatosis. The overall goal is to examine whether hepatic DNL is increased in obese youths with steatosis compared to matched controls without steatosis.

Hypotheses: Hepatic conversion of carbohydrates to lipid (DNL) is enhanced and is associated with accumulation of excess liver fat, dyslipidemia and hepatic insulin resistance in obese youths with hepatic steatosis.


Condition or disease
Hepatic Steatosis Fatty Liver

Detailed Description:
In this study obese youths (12-18 years) will undergo MRI (magnetic resonance imaging) measurement of liver lipid content to determine hepatic fat content. They will undergo a sugary drink (75 grams of glucose and 25 grams of fructose) challenge and Hepatic de novo lipogenesis will be determined as the incorporation of deuterium, from deuterium labeled water (D2O), into plasma triglycerides. Subjects will undergo a 6 hours study assessing de novo lipogenesis, an oral glucose tolerance test, dual energy x-ray absorptiometry, magnetic resonance imaging, and Euglycemic-Hyperinsulinemic Clamp.

Study Design

Study Type : Observational
Actual Enrollment : 14 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: The Role of Hepatic De Novo Lipogenesis (DNL) in the Pathogenesis of Hepatic Steatosis in Obese Children and Adolescents
Study Start Date : December 2010
Primary Completion Date : April 2016
Study Completion Date : April 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Groups and Cohorts

Group/Cohort
Fatty liver
Non Fatty liver


Outcome Measures

Primary Outcome Measures :
  1. de novo lipogenesis response to high carbohydrate meal in obese kids with fatty liver [ Time Frame: Study visit 3 ]

Secondary Outcome Measures :
  1. de novo lipogenesis response to high carbohydrate meal in obese kids without fatty liver [ Time Frame: Study visit 3 ]

Biospecimen Retention:   Samples With DNA
Serum

Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   12 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. Following the oral glucose tolerance test (OGTT):normal glucose tolerant if plasma glucose at two hours is <140 mg/dl and impaired glucose tolerant if plasma glucose is ≥140 mg/dl. All subjects must be in good general health, have a normal medical history and physical exam, and have no endocrinopathies or other diseases that might affect glucose metabolism. They will not be on any medications that are known to alter glucose or insulin metabolism or certain psychiatric medications. Subjects determined to be eligible will receive a MRI to determine Hepatic Fat Content. Subjects will agree to genetic testing to determine genotype.
Criteria

Inclusion Criteria:

  • Cases will meet the following criteria:

    • Age between 12 and 18 years
    • BMI higher than 85th percentile
    • Hepatic fat fraction (the amount of fat into the liver) greater or equal than 5.5%
    • Absence of any endocrinopathy
    • Absence of any therapy with medication known to alter glucose metabolism

Controls will meet the following criteria:

  • Age between 12 and 18 years
  • BMI higher than 85th percentile
  • Hepatic fat fraction (the amount of fat into the liver) lower than 5.5%
  • Absence of any endocrinopathy
  • Absence of any therapy with medication known to alter glucose metabolism

Exclusion Criteria:

  • BMI under the 85th percentile

    • Hepatic fat fraction (the amount of fat into the liver) less than 5.5%
    • Absence of any endocrinopathy
    • Any therapy with medication known to alter glucose metabolism

Controls will meet the following criteria:

  • BMI under the 85th percentile
  • Hepatic fat fraction (the amount of fat into the liver) greater than or equal to 5.5%
  • Any endocrinopathy
  • Any therapy with medication known to alter glucose metabolism
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): NCT01725035


Locations
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06510
Sponsors and Collaborators
Yale University
American Heart Association
Investigators
Principal Investigator: Sonia Caprio, M.D. Yale University
Principal Investigator: Nicola Santoro, M.D./Ph.D, Yale University
More Information

Responsible Party: Sonia Caprio, Professor of Pediatrics, Yale University
ClinicalTrials.gov Identifier: NCT01725035     History of Changes
Other Study ID Numbers: 1008007192
11CRP5620013 ( Other Grant/Funding Number: American Heart Association )
First Posted: November 12, 2012    Key Record Dates
Last Update Posted: April 7, 2016
Last Verified: April 2016

Keywords provided by Sonia Caprio, Yale University:
De Novo Lipogenesis
Fatty Liver
Hepatic Steatosis
Gene variants

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases