Non Alcoholic Fatty Liver DiseaseNCT01966627
Genetics of Fatty Liver Disease in Children
An observational study of Non Alcoholic Fatty Liver Disease, run by Yale University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 7 to 18 years
- Conditions the study is for
- Non Alcoholic Fatty Liver Disease
- What is being tested?
- ogtt, genotyping and abdominal and liver magnetic resonance imaging
- Type of treatment
- Pill or oral medicine
- How many people
- 381 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Jul 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: The majority of the research subjects will be recruited from the Yale Pediatric Obesity Clinic and the Endocrine Clinic.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Genetics of Fatty Liver Disease in Childhood Obesity.
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.
Read the 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.
- Conditions
- Non Alcoholic Fatty Liver Disease
- Being tested
- ogtt, genotyping, abdominal and liver magnetic resonance imaging, stool sample, liver biopsy
- Keywords
- non alcoholic fatty liver, childhood obesity, genetic variants
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Pediatric Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ogttOther
oral glucose tolerance test
genotypingOther
genotyping to look for risk alleles
abdominal and liver magnetic resonance imagingOther
magnetic resonance imaging scan of abdomen and liver - abdominal and liver mri
stool sampleOther
stool sample taken to investigate metabolites
liver biopsyOther
liver biopsy to examine for cellular change and steatosis
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: ogtt; Other: genotyping; Other: abdominal and liver magnetic resonance imaging; Other: stool sample; Other: liver biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
gene expression
gene mutation allele variation identification measure via gene extraction
Measured: Baseline
Secondary outcomes (2)
hepatic fat content
Abdominal MRI to measure liver fat and subcutaneous and visceral fat ratio done at baseline and 2 year follow up
Measured: 2 years
glucose tolerance
glucose tolerance status measured by 3 hour oral glucose tolerance test done at baseline and 2 year follow up
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2013 (estimated)
- Study startJul 2011
- Primary completionJul 2017
- Study completionJul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Non Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 381 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Sonia Caprio, Yale University
- Investigators
- Sonia Caprio, M.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01966627
- Sponsor's protocol ID
- 1104008388
- Other IDs
- R01HD040787
- Status last verified
- Dec 2017
- First submitted
- 15 Jul 2013
- Last updated
- 8 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 16912127Trico 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.
PubMed 29665034
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetics of Fatty Liver Disease in Childhood Obesity.
- ClinicalTrials.gov ID
- NCT01966627
- Acronym / sponsor ID
- 1104008388
- Conditions
- Non Alcoholic Fatty Liver Disease
- Keywords
- non alcoholic fatty liver, childhood obesity, genetic variants
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 381 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Jul 2011
- Primary completion
- Jul 2017 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 21 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pediatric NAFLD Cohort | – | Other: ogtt, Other: genotyping, Other: abdominal and liver magnetic resonance imaging, Other: stool sample, Other: liver biopsyOverweight 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. |
Who may qualify
- Ages
- 7 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- The majority of the research subjects will be recruited from the Yale Pediatric Obesity Clinic and the Endocrine Clinic.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ogttoral glucose tolerance test | Other | Pediatric NAFLD Cohort |
| genotypinggenotyping to look for risk alleles | Other | Pediatric NAFLD Cohort |
| abdominal and liver magnetic resonance imagingmagnetic resonance imaging scan of abdomen and liver - abdominal and liver mri | Other | Pediatric NAFLD Cohort |
| stool samplestool sample taken to investigate metabolites | Other | Pediatric NAFLD Cohort |
| liver biopsyliver biopsy to examine for cellular change and steatosis | Other | Pediatric NAFLD Cohort |
Primary outcome
gene expression
Time frame: Baseline
gene mutation allele variation identification measure via gene extraction
2 secondary outcomes
hepatic fat content
Time frame: 2 years
glucose tolerance
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2017.
- Background: PubMed 16912127Burgert 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.
- Derived from this study: PubMed 29665034Trico 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sonia Caprio, M.D. principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Non Alcoholic Fatty Liver Disease, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
gene expression (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01966627, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2017.