Metabolic Tests for Pediatric Non-alcoholic Fatty Liver Disease

Overseen by Kevin Short, PhD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Oklahoma

Must not be taking: Weight loss drugs, glucocorticoids

Disqualifiers: Chronic illness, acute illness, pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial involves taking blood and liver tissue samples from children with NAFLD to understand the disease better. It focuses on this group because they are at higher risk of rapid disease progression. Researchers aim to find specific changes in the liver and blood that can help diagnose and understand NAFLD in children.

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.

How does this treatment for pediatric non-alcoholic fatty liver disease differ from others?

This treatment uses the Single Point Insulin Sensitivity Estimator (SPISE), a novel and inexpensive method to estimate insulin resistance in children with non-alcoholic fatty liver disease, which is more effective than traditional methods. ^{1 2 3 4 5}

Research Team

Kevin Short, PhD

Principal Investigator

University of Oklahoma

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Cardiometabolic testing (Behavioural Intervention)
• De novo lipogenesis test (Behavioural Intervention)
• Gluconeogenesis test (Behavioural Intervention)
• Oral sugar tolerance test (Behavioural Intervention)

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.

Participant Groups

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+

Dr. Scott Rollins

University of Oklahoma

Chief Executive Officer since 2016

PhD in Immunology from the University of Oklahoma

Dr. Ondria Gleason

University of Oklahoma

Chief Medical Officer

MD from the University of Oklahoma College of Medicine

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Dr. Griffin P. Rodgers

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

Chief Executive Officer since 2007

MD, M.A.C.P.

Dr. Griffin P. Rodgers

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

Chief Medical Officer since 2007

MD, M.A.C.P.

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Dr. Jeanne Marrazzo

National Institutes of Health (NIH)

Chief Medical Officer

MD from University of California, Los Angeles

Dr. Jay Bhattacharya

National Institutes of Health (NIH)

Chief Executive Officer

MD, PhD from Stanford University

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Impaired glucose tolerance and type 2 diabetes mellitus: a new field for pediatrics in Europe. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Single Point Insulin Sensitivity Estimator in Pediatric Non-Alcoholic Fatty Liver Disease. [2022]

3. England 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Repetitiveness of the oral glucose tolerance test in children and adolescents. [2021]