Metabolic Tests for Pediatric Non-alcoholic Fatty Liver Disease

Overseen By Kevin Short, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Oklahoma

Must not be taking: Weight loss drugs, glucocorticoids

Disqualifiers: Chronic illness, acute illness, pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores why some children develop non-alcoholic fatty liver disease (NAFLD) and how it progresses. Researchers are testing various metabolic processes, such as how the liver produces glucose and lipids, to determine if these link to NAFLD. They are also examining blood markers that might help identify the disease early. Children who are obese and diagnosed with NAFLD, or those in the normal weight range without liver issues, might be suitable for this study. As an unphased trial, this study offers a unique opportunity to contribute to understanding NAFLD in children and potentially improve early detection methods.

Will I have to stop taking my current medications?

You can continue taking medications for asthma, allergies, anxiety, depression, attention deficit disorder, menstrual cycle, hypothyroidism, gastric reflux, hypertension, and sleep. However, if you're on medications that affect weight loss or are experimental for metabolic or liver conditions, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have not directly evaluated the safety of the tests used in this trial. However, these tests aim to understand bodily functions, not to introduce new drugs or treatments.

The tests, which assess heart and metabolic health, fat production, sugar production, and sugar processing, are designed to examine how the body handles sugars and fats. No evidence suggests these tests harm participants. Researchers commonly use them to study conditions like non-alcoholic fatty liver disease (NAFLD) in children.

Since this trial is in a "Not Applicable" phase, it focuses on learning about the disease rather than treating it. This suggests the procedures are primarily observational, with minimal risk involved. Participants can expect these tests to be manageable, as they are non-invasive and widely used in clinical research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these tests because they offer a deeper understanding of how pediatric non-alcoholic fatty liver disease (NAFLD) develops and progresses. Unlike current options that focus primarily on lifestyle changes like diet and exercise, these metabolic tests aim to pinpoint specific metabolic dysfunctions that contribute to the disease. By examining factors like de novo lipogenesis (how the liver creates fat) and gluconeogenesis (how the liver produces glucose), these tests could lead to more precise and personalized treatment approaches. This trial's innovative approach could pave the way for targeted therapies that address the root metabolic causes of NAFLD in children.

What evidence suggests that this trial's tests could be effective for pediatric NAFLD?

This trial will evaluate various metabolic tests to understand pediatric non-alcoholic fatty liver disease (NAFLD). Research has shown that children with NAFLD often produce more sugar and fat in their liver, potentially influenced by specific differences in RNA and proteins. Studies also indicate that de novo lipogenesis, the body's process of turning sugar into fat, plays a key role in the development of NAFLD. Participants will undergo tests related to heart and metabolism, which often reveal a connection between obesity and NAFLD in children, suggesting that managing weight might help lower the risk. Additionally, tests like gluconeogenesis and oral sugar tolerance will assess how the liver processes sugars and fats, aiding in the management of NAFLD. These findings suggest these tests could be valuable tools for identifying and monitoring NAFLD in young patients. ^{1 4 6 7 8}

Who Is on the Research Team?

Kevin Short, PhD

Principal Investigator

University of Oklahoma

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 10 to 20.9 years with obesity or normal weight, including those diagnosed with NAFLD confirmed by liver biopsy. It's open to all genders and ethnicities. Those with chronic illnesses affecting metabolism, acute conditions, on certain medications, pregnant individuals, or substance abusers cannot participate.

Inclusion Criteria

Race/Ethnicity: Participants of all racial/ethnic identities will be recruited

I am scheduled for a liver biopsy to confirm NAFLD, or I do not have NAFLD.

My BMI is in the normal or obese range according to my age and sex.

Exclusion Criteria

I do not have chronic illnesses that could affect my participation.

I am not taking any medications or supplements that affect weight, metabolism, or liver conditions.

Smoking, alcohol abuse, or illicit drug abuse: Participants who smoke or show signs of alcohol or substance abuse will be excluded

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Testing

Participants undergo metabolic and descriptive tests, including blood analyses and liver biopsy for the NAFLD group

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after testing

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cardiometabolic testing
• De novo lipogenesis test
• Gluconeogenesis test
• Oral sugar tolerance test

Trial Overview The study investigates metabolic changes in the liver of pediatric patients with NAFLD using tests that measure how the liver produces glucose and lipids (fats) and how it processes sugar. The goal is to identify biomarkers in blood that can indicate NAFLD.

How Is the Trial Designed?

Group I: Ob control Experimental Treatment 3 Interventions

Participants with obesity, without NAFLD

Group II: NW control Experimental Treatment 3 Interventions

Participants in the normal range for body weight, without NAFLD

Group III: NAFLD Experimental Treatment 3 Interventions

Participants in the pediatric NAFLD clinic

Group IV: Liver control Experimental Treatment 3 Interventions

Participants undergoing liver biopsy or liver surgery, without NAFLD

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

The oral glucose tolerance test (OGTT) is a reliable method for diagnosing type 2 diabetes mellitus (T2DM) in children and adolescents, but may require multiple tests to accurately diagnose milder glucose impairments like impaired fasting glucose (IFG) and impaired glucose tolerance (IGT).

In this study of 81 children and adolescents, those who were overweight or obese showed higher insulin and C-peptide levels during the OGTT, indicating that excess weight and family history of T2DM can negatively impact glucose metabolism from a young age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitiveness of the oral glucose tolerance test in children and adolescents. Kostopoulou, E., Skiadopoulos, S., Partsalaki, I., et al.[2021]

In a study of 102 high-risk obese children, 6 were diagnosed with type 2 diabetes and 37 with impaired glucose tolerance, highlighting the significant risk of glucose metabolism disturbances in this population.

The findings suggest a strong link between impaired glucose tolerance and abnormal triglyceride and cholesterol levels, emphasizing the importance of early diagnosis and monitoring of obesity-related health risks in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impaired glucose tolerance and type 2 diabetes mellitus: a new field for pediatrics in Europe. Wiegand, S., Dannemann, A., Krude, H., et al.[2022]

In a study of 43 children with biopsy-proven nonalcoholic fatty liver disease (NAFLD), 95% were found to have insulin resistance, highlighting its prevalence and importance in this population.

Significant predictors of liver pathology were identified, including insulin sensitivity, age, ethnicity, and specific clinical symptoms, suggesting that screening for insulin resistance is crucial for evaluating liver health in children with NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. Schwimmer, JB., Deutsch, R., Rauch, JB., et al.[2022]

In a study of 63 prepubertal children with obesity, a 9-month standard treatment led to significant reductions in liver enzyme levels (ALT), insulin resistance (HOMA-IR), and inflammation markers (CRP, IL-6).

The decrease in ALT levels was associated with improvements in leptin levels and various inflammation biomarkers, indicating that effective obesity treatment can positively impact liver health and metabolic parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in liver enzymes are associated with changes in insulin resistance, inflammatory biomarkers and leptin in prepubertal children with obesity. Valle-Martos, R., Jiménez-Reina, L., Cañete, R., et al.[2023]

The single point insulin sensitivity estimator (SPISE) is a novel and cost-effective index that effectively measures hepatic insulin resistance in children and adolescents with obesity, showing lower values in those with non-alcoholic fatty liver disease (NAFLD) compared to those without.

In a study of 99 pubertal subjects, SPISE demonstrated superior diagnostic ability for hepatic insulin resistance compared to established indices like HOMA-IR and HIRI, with a sensitivity of 68% and specificity of 67% at an optimal cutoff level of 5.18.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single Point Insulin Sensitivity Estimator in Pediatric Non-Alcoholic Fatty Liver Disease. Furthner, D., Anderwald, CH., Bergsten, P., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2797656/

Pediatric non-alcoholic fatty liver disease - PubMed Central Here, we outline the clinical course, pathogenesis and management of NAFLD in children, highlighting the preventive and therapeutic value of lifestyle ...

2. cardiometabolichealth.org cardiometabolichealth.org/wp-content/uploads/2023/04/09_Pediatric-Non-alcoholic-Fatty-Liver-Disease-Assessment-and-Management-Stavra-Xanthakos-MD.pdf

Pediatric Non-Alcoholic Fatty Liver Disease Current NAFLD Diagnosis does not require obesity or metabolic risk criteria ... No longitudinal correlation data with disease progression and outcomes.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5037077/

Pediatric non-alcoholic fatty liver disease - PubMed Central Remarkably, the overall prevalence of NAFLD in children has reached approximately 10%, including up to 17% in teenagers and 40%-70% among obese children. While ...

4. tandfonline.com tandfonline.com/doi/full/10.2147/PHMT.S188989

Full article: Pediatric non-alcoholic fatty liver disease Recent data showed positive outcomes such as reduction in BMI and NAFLD ... liver disease in childhood with potential serious cardiometabolic ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0168827821018833

Non-alcoholic fatty liver disease in children and young ... Children and young adults with biopsy-confirmed NAFLD and NASH have significantly higher rates of overall, cancer-, liver- and cardiometabolic-specific ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3158407/

Pediatric nonalcoholic fatty liver disease, metabolic syndrome ... NAFLD is strongly associated with abdominal obesity, type 2 diabetes, and dyslipidemia, and most patients have evidence of insulin resistance.

7. sciencedirect.com sciencedirect.com/science/article/pii/S258953702300425X

Risk factors and cardio-metabolic outcomes associated ... We assessed the prevalence, early-life risk factors and cardio-metabolic outcomes associated with MAFLD in childhood, in a general pediatric population.

8. mdpi.com mdpi.com/2227-9067/12/1/71

Pediatric Non-Alcoholic Fatty Liver Disease (NAFLD) Conclusions: Our study has shown ever increasing hospitalization rates for NAFLD in pediatric populations and well as significant risk factors associated with ...