Hepatic SteatosisDNLNCT01725035
Hepatic De Novo Lipogenesis (DNL)in the Pathogenesis of Hepatic Steatosis in Obese Youth
An observational study of Hepatic Steatosis and Fatty Liver, run by Yale University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 to 30 years
- Conditions the study is for
- Hepatic Steatosis, Fatty Liver
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2010to 10 Aug 2022
- 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 12 to 30 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. 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.
Who may be able to join
- Cases will meet the following criteria:
- BMI higher than 75th 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:
Show all 11Show fewer
- BMI higher than 75th 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
- Absence of any therapy with medication known to alter glucose metabolism
Who cannot join
- BMI under the 75th 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 75th percentile
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Role of Hepatic De Novo Lipogenesis (DNL) in the Pathogenesis of Hepatic Steatosis in Obese Children and Adolescents
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.
Read the detailed description
In this study obese youths, adolescents and young adults (12-30 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.
This study record has been re-opened in 2019 and updated to reflect any changes having remained open since its inception with the Yale University IRB and also having obtained additional funding though NIDDK.
- Conditions
- Hepatic Steatosis, Fatty Liver
- Keywords
- De Novo Lipogenesis, Fatty Liver, Hepatic Steatosis, Gene variants
- Medical subject headings
- Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Fatty liver | Not described | |
| Non Fatty liver | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
de novo lipogenesis response to high carbohydrate meal in obese kids with fatty liver
Measured: Study visit 3
Secondary outcomes (1)
de novo lipogenesis response to high carbohydrate meal in obese kids without fatty liver
Measured: Study visit 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2012 (estimated)
- Study startDec 2010
- Primary completion10 Aug 2022
- Study completion10 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic SteatosisStudies 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor
- Investigators
- Sonia Caprio, M.D., Principal investigator, Yale UniversityNicola Santoro, M.D./Ph.D,, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01725035
- Sponsor's protocol ID
- 1008007192
- Other IDs
- 11CRP5620013, 1R01DK114504-01A1
- Acronym
- DNL
- Status last verified
- Jun 2023
- First submitted
- 30 Oct 2012
- Last updated
- 15 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Hepatic De Novo Lipogenesis (DNL) in the Pathogenesis of Hepatic Steatosis in Obese Children and Adolescents
- ClinicalTrials.gov ID
- NCT01725035
- Acronym / sponsor ID
- DNL / 1008007192
- Conditions
- Hepatic Steatosis, Fatty Liver
- Keywords
- De Novo Lipogenesis, Fatty Liver, Hepatic Steatosis, Gene variants
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- American Heart Association, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Dec 2010 (actual)
- Primary completion
- 10 Aug 2022 (actual)
- Study completion
- 10 Aug 2022 (actual)
- First posted
- 12 Nov 2012 (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.
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.
Detailed description
In this study obese youths, adolescents and young adults (12-30 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.
This study record has been re-opened in 2019 and updated to reflect any changes having remained open since its inception with the Yale University IRB and also having obtained additional funding though NIDDK.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fatty liver | – | – |
| Non Fatty liver | – | – |
Who may qualify
- Ages
- 12 to 30 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. 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.
Key inclusion criteria (11 listed)
- Cases will meet the following criteria:
- BMI higher than 75th 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
Key exclusion criteria (9 listed)
- BMI under the 75th 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
- BMI under the 75th percentile
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
de novo lipogenesis response to high carbohydrate meal in obese kids with fatty liver
Time frame: Study visit 3
1 secondary outcome
de novo lipogenesis response to high carbohydrate meal in obese kids without fatty liver
Time frame: Study visit 3
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 15 Jun 2023.
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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
Nicola Santoro, M.D./Ph.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 Hepatic Steatosis and Fatty Liver, 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 11 inclusion and 9 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 15 Jun 2023. 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?
de novo lipogenesis response to high carbohydrate meal in obese kids with fatty liver (time frame: Study visit 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jun 2023.