NAFLDNCT04634643
Pathogenesis of Pediatric Nonalcoholic Fatty Liver Disease (NAFLD)
An observational study of NAFLD, run by Yale University at 1 site in United States.
Trial summary
The main aim of the study is to discover the mechanisms underlying the pathophysiology of NAFLD in obese youth. Read more about this study
- Who is it for?
- Ages 12 to 18 years
- Conditions the study is for
- NAFLD
- What is being tested?
- Usual diet and physical activity
- How many people
- 260 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Jun 2021to 30 Jan 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 18 years
- All sexes
- Child, Adult
Study population: Hispanics and NHB youth with and without NAFLD
Who may be able to join
- Good general health, taking no medication on a chronic basis;
- age 12 to 18 years, in puberty (girls and boys: Tanner stage II-V);
- BMI >85th for obese cohort;
Who cannot join
- Baseline creatinine >1.0 mg; pregnancy;
- the presence of endocrinopathies (e.g. Cushing syndrome);
- cardiac or pulmonary or other significant chronic illness;
- adolescents with a psychiatric disorder or with substance abuse;
- monogenic obesity syndromes;
- use of drugs affecting intrahepatic fat content (e.g.; liraglutide, fish oil, etc.).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Yale New Haven Hospital
New Haven, Connecticut, 06510
Ermena Refugjati, 203-215-7119, ermena.refugjati@yale.edu
Nicola Santoro, MD, PhD
About this study
Official title: Pathophysiologic Mechanisms Leading to Intrahepatic Fat Accumulation in Obese Youth
The main aim of the study is to discover the mechanisms underlying the pathophysiology of NAFLD in obese youth.
Read the detailed description
Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disease in pediatrics, affecting about 30% of obese youth. The term NAFLD defines a wide spectrum of disease severity ranging from simple intrahepatic fat accumulation without liver injury (steatosis) to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis.
A 20-year retrospective study has shown that subjects who develop NAFLD during their youth have about 13 times higher mortality rate for end-stage liver disease than healthy subjects of similar age and gender. NAFLD is highly prevalent among Hispanic youth, while non-Hispanic Black (NHB) youth are protected against intrahepatic fat accumulation even in the presence of severe obesity and insulin resistance. Understanding the pathophysiology underlying these differences could shed new light on the mechanisms leading to NAFLD in obese youth.
Preliminary data suggest that Hispanic and NHB obese youth might have a different ability to metabolize carbohydrates (CHO) through glycolysis, with Hispanics showing higher glycolysis than NHB. Therefore, Hispanics might experience a higher rated tricyclic acid cycle (TCA) and hepatic de novo lipogenesis (DNL).
In the present study, the investigators aim to address the following questions:
- Is the different susceptibility between Hispanics and NHB in developing NAFLD due to a higher capability of Hispanics to metabolize CHO through glycolysis, TCA cycle and DNL?
- Do these metabolic changes anticipate the onset of the disease in Hispanic youth?
- Are the higher rates of glycolysis, TCA and DNL driven by high but not pathologic changes in glucose levels over time?
To address these aims, the investigators plan to recruit 30 Hispanics and 30 NHB obese youth and to measure glycolysis by using a new method to assess lactate kinetics and to determine the TCA cycle and DNL by using 13C-Propionate and D2O.
The investigators will also assess glycolysis and intrahepatic fat content in a group of 200Hispanic obese youth without fatty liver at baseline every 12 months for two years to determine whether higher glycolytic rates precede intrahepatic fat accumulation. To assess whether metabolic changes in glycolysis are driven by higher but not-pathologic glucose levels, the investigators will measure glucose changes over ten days every six months by using a continuous glucose monitoring system. If successful, these studies will provide novel insight into the pathogenesis of pediatric NAFLD and will open new avenues to test novel therapeutic approaches.
Study was paused in 2022 and reopened recruitment in November 2023.
- Conditions
- NAFLD
- Being tested
- Usual diet and physical activity
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Usual diet and physical activityOther
Patients will be followed up to assess the effect of the usual diet and physical activity on development of NAFLD
What is being measured
The primary outcome is the main question the study is designed to answer.
Lactate synthesis
lactate synthesis will be measured during an oral glucose tolerance test by measuring lactate. Synthetic rates will be measured by using a mathematical model.
Measured: 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2020
- Study start28 Jun 2021
- Primary completion30 Jan 2027 (estimated)
- Study completion30 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NAFLDStudies 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
- 260 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Minority Health and Health Disparities (NIMHD)
- Responsible party
- Sponsor
- Investigators
- Nicola Santoro, MD, PhD, Principal investigator, Associate Professor of Pediatrics (Endocrinology)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04634643
- Sponsor's protocol ID
- 2000028731
- Other IDs
- R01MD015974
- Status last verified
- Jul 2026
- First submitted
- 17 Nov 2020
- Last updated
- 30 Jul 2026
- 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 30 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pathophysiologic Mechanisms Leading to Intrahepatic Fat Accumulation in Obese Youth
- ClinicalTrials.gov ID
- NCT04634643
- Acronym / sponsor ID
- 2000028731
- Conditions
- NAFLD
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 260 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Minority Health and Health Disparities (NIMHD)
- Study start
- 28 Jun 2021 (actual)
- Primary completion
- 30 Jan 2027 (estimated)
- Study completion
- 30 Jan 2027 (estimated)
- First posted
- 18 Nov 2020 (actual)
- 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.
The main aim of the study is to discover the mechanisms underlying the pathophysiology of NAFLD in obese youth.
Detailed description
Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disease in pediatrics, affecting about 30% of obese youth. The term NAFLD defines a wide spectrum of disease severity ranging from simple intrahepatic fat accumulation without liver injury (steatosis) to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis.
A 20-year retrospective study has shown that subjects who develop NAFLD during their youth have about 13 times higher mortality rate for end-stage liver disease than healthy subjects of similar age and gender. NAFLD is highly prevalent among Hispanic youth, while non-Hispanic Black (NHB) youth are protected against intrahepatic fat accumulation even in the presence of severe obesity and insulin resistance. Understanding the pathophysiology underlying these differences could shed new light on the mechanisms leading to NAFLD in obese youth.
Preliminary data suggest that Hispanic and NHB obese youth might have a different ability to metabolize carbohydrates (CHO) through glycolysis, with Hispanics showing higher glycolysis than NHB. Therefore, Hispanics might experience a higher rated tricyclic acid cycle (TCA) and hepatic de novo lipogenesis (DNL).
In the present study, the investigators aim to address the following questions:
- Is the different susceptibility between Hispanics and NHB in developing NAFLD due to a higher capability of Hispanics to metabolize CHO through glycolysis, TCA cycle and DNL?
- Do these metabolic changes anticipate the onset of the disease in Hispanic youth?
- Are the higher rates of glycolysis, TCA and DNL driven by high but not pathologic changes in glucose levels over time?
To address these aims, the investigators plan to recruit 30 Hispanics and 30 NHB obese youth and to measure glycolysis by using a new method to assess lactate kinetics and to determine the TCA cycle and DNL by using 13C-Propionate and D2O.
The investigators will also assess glycolysis and intrahepatic fat content in a group of 200Hispanic obese youth without fatty liver at baseline every 12 months for two years to determine whether higher glycolytic rates precede intrahepatic fat accumulation. To assess whether metabolic changes in glycolysis are driven by higher but not-pathologic glucose levels, the investigators will measure glucose changes over ten days every six months by using a continuous glucose monitoring system. If successful, these studies will provide novel insight into the pathogenesis of pediatric NAFLD and will open new avenues to test novel therapeutic approaches.
Study was paused in 2022 and reopened recruitment in November 2023.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 12 to 18 years
- Sex
- All
- Age groups
- Child, Adult
- Study population
- Hispanics and NHB youth with and without NAFLD
Key inclusion criteria (3 listed)
- Good general health, taking no medication on a chronic basis;
- age 12 to 18 years, in puberty (girls and boys: Tanner stage II-V);
- BMI >85th for obese cohort;
Key exclusion criteria (6 listed)
- Baseline creatinine >1.0 mg; pregnancy;
- the presence of endocrinopathies (e.g. Cushing syndrome);
- cardiac or pulmonary or other significant chronic illness;
- adolescents with a psychiatric disorder or with substance abuse;
- monogenic obesity syndromes;
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 |
|---|---|---|
| Usual diet and physical activityPatients will be followed up to assess the effect of the usual diet and physical activity on development of NAFLD | Other | – |
Primary outcome
Lactate synthesis
Time frame: 60 months
lactate synthesis will be measured during an oral glucose tolerance test by measuring lactate. Synthetic rates will be measured by using a mathematical model.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2026.
Related trials for NAFLD
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NAFLD Clinical Care Pathway
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Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
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RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
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A Study of Efimosfermin Alfa in Participants With Biopsy-confirmed Cirrhosis (Compensated) Due to MASH
Metabolic Dysfunction-Associated Steatohepatitis, Non-alcoholic Fatty Liver Disease
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.
Nicola Santoro, MD, PhD principal investigator
Associate Professor of Pediatrics (Endocrinology)
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 NAFLD, 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 6 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: looking for participants now, as of the sponsor's last update on 30 Jul 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ermena REFUGJATI (2032157119, ermena.refugjati@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lactate synthesis (time frame: 60 months). 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 30 Jul 2026.