Nonalcoholic Fatty LiverNCT05430178
Metabolic Pathology of Pediatric NAFLD
A study testing Oral sugar tolerance test, De novo lipogenesis test and Gluconeogenesis test in people with Nonalcoholic Fatty Liver and Nonalcoholic Steatohepatitis, run by University of Oklahoma at 1 site in United States.
Trial summary
Nonalcoholic fatty liver disease (NAFLD) is now the most common liver disease worldwide and affects nearly 40% of obese youth and up to 10% of the general pediatric population. Some features of NAFLD are similar in children and adults, yet fibrosis and inflammation are more common in the portal zone and occur earlier… Read more about this study
- Who is it for?
- Ages 10 to 20 yearsHealthy volunteers can take part
- Conditions the study is for
- Nonalcoholic Fatty Liver, Nonalcoholic Steatohepatitis, Obesity
- What is being tested?
- Oral sugar tolerance test, De novo lipogenesis test and Gluconeogenesis test
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 25 May 2022to Jun 2026
- Phase
- Interventional
- 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 10 to 20 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Age: All participants must be 10.0 to 20.9 years old at the time of enrollment.
- Sex: Male and Female participants are eligible.
- Race/Ethnicity: Participants of all racial/ethnic identities will be recruited.
- Body mass index (BMI): Participants must be either in the normal weight (NW control group) or obese [Ob control, nonalcoholic fatty liver disease (NALFD) groups] range for BMI percentile. BMI percentile will be calculated from age- and sex-specific growth charts for children.
- NAFLD status: The NAFLD group participants will be eligible if they are scheduled for liver biopsy for clinical reasons and their histopathology report confirms a diagnosis of NAFLD. NW control, and Ob control, and Liver control participants must not have diagnosed NAFLD.
Who cannot join
- Chronic illness: Participants will not be able to participate if they have conditions that are likely to affect metabolic variables (either directly or due to required medications) or result in them being unable to complete the required tests. Such conditions could include, but are not limited to, untreated hypothyroidism or other endocrine disorders, rheumatoid arthritis requiring steroids or limiting mobility, cardiovascular disease, stroke, or cardiac failure, neurological disorders such as multiple sclerosis, cancer, liver diseases other than NAFLD (e.g., Wilson's disease), other organ disorders, or orthopedic conditions that limit physical activity.
- Acute illness: Participants will not be able to participate if they develop acute conditions that are likely to affect metabolic outcomes (either directly or due to required medications) or result in them being unable to participate; e.g., respiratory illness, infectious disease, fever, accident resulting in bone fractures, myocardial infarction, major depression. If such conditions resolve and there are no longer risks or likelihood of adverse effect on the study outcomes, participants may be rescheduled for testing.
- Medications and nutritional supplements: Medications, vitamins, or supplements that have known effects on the primary outcomes will be cause for exclusion. Examples include weight loss medications, glucocorticoids, or experimental medications used to correct a metabolic or hepatic condition. Medications used to control asthma, allergies, anxiety, depression, attention deficit disorder, menstrual cycle, hypothyroidism, gastric reflux, hypertension, and sleep will be allowed. Participants who are taking medications for treatment of acute illness or conditions such as cold, flu, injury, or infection will be rescheduled after they complete their treatment course.
- Pregnancy: Evidence of pregnancy or intent to become pregnant during the study is cause for exclusion.
- Smoking, alcohol abuse, or illicit drug abuse: Participants who smoke or have signs or symptoms of alcohol or substance abuse will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Kevin Short, PhD, 405-271-8001 ext. 43094, kevin-short@ouhsc.edu
About this study
Official title: Understanding the Metabolic Pathology of Pediatric Obesity and NAFLD
Nonalcoholic fatty liver disease (NAFLD) is now the most common liver disease worldwide and affects nearly 40% of obese youth and up to 10% of the general pediatric population. Some features of NAFLD are similar in children and adults, yet fibrosis and inflammation are more common in the portal zone and occur earlier in pediatric NAFLD patients than adults. This portends a rapid progression to end-stage liver disease in early adulthood. For the majority of children with NAFLD, mechanisms driving the origin and rapid progression of disease remain unknown. Thus, there is a critical, unmet need to study the specific underlying patterns of metabolic and molecular changes in the liver underlying the development and progression unique to children with NAFLD.
This proposal will test the hypotheses that children with NAFLD have excess glucose and lipid produced by the liver, that those events are regulated by specific variations in the amount and location of RNAs and proteins in liver, and that the concentration of specific micro-RNAs in the blood can be used as a biomarker for NAFLD in pediatric patients.
Read the detailed description
This project uses a cross-sectional design with a single testing period without a formal intervention (e.g., diet, drug, exercise) or natural follow-up period. Participants with nonalcoholic fatty liver disease (NAFLD), and age-matched control groups classified as either obese (Ob control) or normal weight (NW control) will complete all metabolic and descriptive tests, including blood analyses.
The NAFLD group will also have a liver biopsy as part of their standard clinical care; a portion of the biopsy will be used for the research testing. The Ob and NW control groups will not undergo liver biopsy. To provide a set of reference liver samples to compare with the NAFLD group, we will enroll a "liver control" group, consisting of age-matched patients who are scheduled to have a cholecystectomy with liver biopsy or are undergoing liver resection for tumor removal.
- Being tested
- Oral sugar tolerance test, De novo lipogenesis test, Gluconeogenesis test
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral sugar tolerance testOther
Measurement of glucose and insulin for calculation of insulin sensitivity
De novo lipogenesis testOther
Oral consumption of deuterated water to measure incorporation of label into lipids
Gluconeogenesis testOther
Oral consumption of 13C-labeled glycerol to measure incorporation into glucose
| Study group | Role | What they receive |
|---|---|---|
| NAFLD | Experimental | Participants in the pediatric NAFLD clinic Receives: Other: Oral sugar tolerance test; Other: De novo lipogenesis test; Other: Gluconeogenesis test |
| Ob control | Experimental | Participants with obesity, without NAFLD Receives: Other: Oral sugar tolerance test; Other: De novo lipogenesis test; Other: Gluconeogenesis test |
| NW control | Experimental | Participants in the normal range for body weight, without NAFLD Receives: Other: Oral sugar tolerance test; Other: De novo lipogenesis test; Other: Gluconeogenesis test |
| Liver control | Experimental | Participants undergoing liver biopsy or liver surgery, without NAFLD Receives: Other: Oral sugar tolerance test; Other: De novo lipogenesis test; Other: Gluconeogenesis test |
What is being measured
The primary outcome is the main question the study is designed to answer.
De novo lipogenesis
Measurement of the rate of newly synthesized triglycerides in plasma using deuterated water
Measured: Day 1
Gluconeogenesis
Measurement of the rate newly synthesized glucose in circulation using labeled glycerol and deuterated water
Measured: Day 1
Serum microRNA
Abundance of microRNAs in serum using a broad profiling platform and real-time quantitative polymerase chain reaction tests for confirming individual miRNAs
Measured: Day 1
Abundance of liver collagen
Abundance of collagen in liver biopsy sections, using Second Harmonic Generation microscopy
Measured: Day 1
Liver mitochondrial flux
Reported as the fluorescent lifetime redox ratio (FLIRR), which is calculated from measurements of free and bound NADH and FAD in liver biopsy sections, using fluorescence lifetime imaging microscopy
Measured: Day 1
Insulin sensitivity
Calculated value of insulin sensitivity, using the oral minimal model and serial concentrations of glucose and insulin during an oral sugar tolerance test
Measured: Day 1
Secondary outcomes (2)
Targets of microRNA-122
Transcripts bound to microRNA-122, measured using high-throughput sequencing of cross- linked immunoprecipitates (HITS-CLIP)
Measured: Day 1
Liver transcriptomics
Spatial distribution of messenger RNAs in liver biopsies
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2022
- Study start25 May 2022
- Primary completionFeb 2026 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nonalcoholic Fatty LiverStudies of the same condition, open and under way.
- More trials run by University of OklahomaThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Cross-sectional design in which all participants receive all interventions in the form of short-term observations following oral consumption of test materials.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oklahoma
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kevin Short, PhD, Principal investigator, University of Oklahoma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05430178
- Sponsor's protocol ID
- 14018
- Other IDs
- 1R01DK129656-01A1
- Status last verified
- Mar 2024
- First submitted
- 1 Jun 2022
- Last updated
- 6 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Understanding the Metabolic Pathology of Pediatric Obesity and NAFLD
- ClinicalTrials.gov ID
- NCT05430178
- Acronym / sponsor ID
- 14018
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of OklahomaUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 25 May 2022 (actual)
- Primary completion
- Feb 2026 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 24 Jun 2022 (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.
Nonalcoholic fatty liver disease (NAFLD) is now the most common liver disease worldwide and affects nearly 40% of obese youth and up to 10% of the general pediatric population. Some features of NAFLD are similar in children and adults, yet fibrosis and inflammation are more common in the portal zone and occur earlier in pediatric NAFLD patients than adults. This portends a rapid progression to end-stage liver disease in early adulthood. For the majority of children with NAFLD, mechanisms driving the origin and rapid progression of disease remain unknown. Thus, there is a critical, unmet need to study the specific underlying patterns of metabolic and molecular changes in the liver underlying the development and progression unique to children with NAFLD.
This proposal will test the hypotheses that children with NAFLD have excess glucose and lipid produced by the liver, that those events are regulated by specific variations in the amount and location of RNAs and proteins in liver, and that the concentration of specific micro-RNAs in the blood can be used as a biomarker for NAFLD in pediatric patients.
Detailed description
This project uses a cross-sectional design with a single testing period without a formal intervention (e.g., diet, drug, exercise) or natural follow-up period. Participants with nonalcoholic fatty liver disease (NAFLD), and age-matched control groups classified as either obese (Ob control) or normal weight (NW control) will complete all metabolic and descriptive tests, including blood analyses.
The NAFLD group will also have a liver biopsy as part of their standard clinical care; a portion of the biopsy will be used for the research testing. The Ob and NW control groups will not undergo liver biopsy. To provide a set of reference liver samples to compare with the NAFLD group, we will enroll a "liver control" group, consisting of age-matched patients who are scheduled to have a cholecystectomy with liver biopsy or are undergoing liver resection for tumor removal.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Cross-sectional design in which all participants receive all interventions in the form of short-term observations following oral consumption of test materials.
| Arm | Type | Receives |
|---|---|---|
| NAFLD | Experimental | Other: Oral sugar tolerance test, Other: De novo lipogenesis test, Other: Gluconeogenesis testParticipants in the pediatric NAFLD clinic |
| Ob control | Experimental | Other: Oral sugar tolerance test, Other: De novo lipogenesis test, Other: Gluconeogenesis testParticipants with obesity, without NAFLD |
| NW control | Experimental | Other: Oral sugar tolerance test, Other: De novo lipogenesis test, Other: Gluconeogenesis testParticipants in the normal range for body weight, without NAFLD |
| Liver control | Experimental | Other: Oral sugar tolerance test, Other: De novo lipogenesis test, Other: Gluconeogenesis testParticipants undergoing liver biopsy or liver surgery, without NAFLD |
Who may qualify
- Ages
- 10 to 20 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Age: All participants must be 10.0 to 20.9 years old at the time of enrollment.
- Sex: Male and Female participants are eligible.
- Race/Ethnicity: Participants of all racial/ethnic identities will be recruited.
- Body mass index (BMI): Participants must be either in the normal weight (NW control group) or obese [Ob control, nonalcoholic fatty liver disease (NALFD) groups] range for BMI percentile. BMI percentile will be calculated from age- and sex-specific growth charts for children.
- NAFLD status: The NAFLD group participants will be eligible if they are scheduled for liver biopsy for clinical reasons and their histopathology report confirms a diagnosis of NAFLD. NW control, and Ob control, and Liver control participants must not have diagnosed NAFLD.
Key exclusion criteria (5 listed)
- Chronic illness: Participants will not be able to participate if they have conditions that are likely to affect metabolic variables (either directly or due to required medications) or result in them being unable to complete the required tests. Such conditions could include, but are not limited to, untreated hypothyroidism or other endocrine disorders, rheumatoid arthritis requiring steroids or limiting mobility, cardiovascular disease, stroke, or cardiac failure, neurological disorders such as multiple sclerosis, cancer, liver diseases other than NAFLD (e.g., Wilson's disease), other organ disorders, or orthopedic conditions that limit physical activity.
- Acute illness: Participants will not be able to participate if they develop acute conditions that are likely to affect metabolic outcomes (either directly or due to required medications) or result in them being unable to participate; e.g., respiratory illness, infectious disease, fever, accident resulting in bone fractures, myocardial infarction, major depression. If such conditions resolve and there are no longer risks or likelihood of adverse effect on the study outcomes, participants may be rescheduled for testing.
- Medications and nutritional supplements: Medications, vitamins, or supplements that have known effects on the primary outcomes will be cause for exclusion. Examples include weight loss medications, glucocorticoids, or experimental medications used to correct a metabolic or hepatic condition. Medications used to control asthma, allergies, anxiety, depression, attention deficit disorder, menstrual cycle, hypothyroidism, gastric reflux, hypertension, and sleep will be allowed. Participants who are taking medications for treatment of acute illness or conditions such as cold, flu, injury, or infection will be rescheduled after they complete their treatment course.
- Pregnancy: Evidence of pregnancy or intent to become pregnant during the study is cause for exclusion.
- Smoking, alcohol abuse, or illicit drug abuse: Participants who smoke or have signs or symptoms of alcohol or substance abuse will be 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 |
|---|---|---|
| Oral sugar tolerance testMeasurement of glucose and insulin for calculation of insulin sensitivity | Other | Liver control, NAFLD, NW control, Ob control |
| De novo lipogenesis testOral consumption of deuterated water to measure incorporation of label into lipids | Other | Liver control, NAFLD, NW control, Ob control |
| Gluconeogenesis testOral consumption of 13C-labeled glycerol to measure incorporation into glucose | Other | Liver control, NAFLD, NW control, Ob control |
Primary outcome
De novo lipogenesis
Time frame: Day 1
Measurement of the rate of newly synthesized triglycerides in plasma using deuterated water
Gluconeogenesis
Time frame: Day 1
Measurement of the rate newly synthesized glucose in circulation using labeled glycerol and deuterated water
Serum microRNA
Time frame: Day 1
Abundance of microRNAs in serum using a broad profiling platform and real-time quantitative polymerase chain reaction tests for confirming individual miRNAs
Abundance of liver collagen
Time frame: Day 1
Abundance of collagen in liver biopsy sections, using Second Harmonic Generation microscopy
Liver mitochondrial flux
Time frame: Day 1
Reported as the fluorescent lifetime redox ratio (FLIRR), which is calculated from measurements of free and bound NADH and FAD in liver biopsy sections, using fluorescence lifetime imaging microscopy
Insulin sensitivity
Time frame: Day 1
Calculated value of insulin sensitivity, using the oral minimal model and serial concentrations of glucose and insulin during an oral sugar tolerance test
2 secondary outcomes
Targets of microRNA-122
Time frame: Day 1
Liver transcriptomics
Time frame: Day 1
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2024.
- Individual participant dataSharing planned: Undecided
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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.
Kevin Short, PhD principal investigator
University of Oklahoma
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Oral sugar tolerance test, De novo lipogenesis test and Gluconeogenesis test in people with Nonalcoholic Fatty Liver and Nonalcoholic Steatohepatitis, run by University of Oklahoma 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 5 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 6 Mar 2024. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kevin Short, PhD (405-271-8001 ext. 43094, kevin-short@ouhsc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
De novo lipogenesis (time frame: Day 1). The study lists 6 primary outcomes in all. 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 6 Mar 2024.