Metabolic Pathology of Pediatric NAFLD

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age10-20
SponsorUniversity of Oklahoma

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Oral sugar tolerance test

    Other intervention

    Measurement of glucose and insulin for calculation of insulin sensitivity

  • De novo lipogenesis test

    Other intervention

    Oral consumption of deuterated water to measure incorporation of label into lipids

  • Gluconeogenesis test

    Other intervention

    Oral consumption of 13C-labeled glycerol to measure incorporation into glucose

Treatment groups

100 Participants
are divided into 4 treatment groups
Group A: NAFLDExperimental treatment 3 interventions
Group B: Ob controlExperimental treatment 3 interventions
Group C: NW controlExperimental treatment 3 interventions
Group D: Liver controlExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

De novo lipogenesis

Measurement of the rate of newly synthesized triglycerides in plasma using deuterated water

Time frame
Day 1
2

Gluconeogenesis

Measurement of the rate newly synthesized glucose in circulation using labeled glycerol and deuterated water

Time frame
Day 1
3

Serum microRNA

Abundance of microRNAs in serum using a broad profiling platform and real-time quantitative polymerase chain reaction tests for confirming individual miRNAs

Time frame
Day 1
4

Abundance of liver collagen

Abundance of collagen in liver biopsy sections, using Second Harmonic Generation microscopy

Time frame
Day 1

Secondary outcomes

1

Targets of microRNA-122

Transcripts bound to microRNA-122, measured using high-throughput sequencing of cross- linked immunoprecipitates (HITS-CLIP)

Time frame
Day 1
2

Liver transcriptomics

Spatial distribution of messenger RNAs in liver biopsies

Time frame
Day 1

Other outcomes

1

Blood pressure

Brachial and central blood pressures

Time frame
Day 1
2

Arterial stiffness

Measured as carotid-femoral pulse wave velocity

Time frame
Day 1
3

Body composition

Whole body and regional lean and fat mass, measure with dual energy X-ray absorptiometry

Time frame
Day 1
4

Cardiorespiratory fitness

Peak oxygen consumption during bicycle ergometry test to volitional fatigue

Time frame
Day 1

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Oklahoma

Lead sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator