Dietary Treatment Study of Pediatric NAFLD

Study Overview
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Brief Summary
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This is an investigator initiated study being conducted in equal numbers at two sites, University of California, San Diego (UC San Diego) and Emory University (EU). The purpose of this study is to understand the potential of a low sugar diet for the treatment of nonalcoholic fatty liver disease (NAFLD) in children. Forty boys with NAFLD will be randomly assigned to either an intervention group or a habitual diet control group. The intervention will be a low sugar diet for a period of 8 weeks. The effect of this dietary change will be assessed using advanced magnetic resonance imaging (MRI) testing to measure liver fat.

Official Title
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Randomized, Controlled Dietary Treatment Study of Pediatric NAFLD

Conditions
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Nonalcoholic Fatty Liver Disease

Intervention / Treatment
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* Other: Dietary modification


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Boys age 11-16 years inclusive. Clinical history consistent with NAFLD. Biopsy-proven NAFLD MRI measured Liver Proton Density Fat Fraction ≥10% alanine aminotransferase (ALT) ≥ 45 u/L No evidence of any other liver disease by clinical history or histological evaluation. Written informed consent from parent or legal guardian. Written informed assent from the child or adolescent. Exclusion Criteria: Exclusions will not be based upon gender, race, or ethnicity. Participants with a current history of the following conditions or any other health issues that make it unsafe for them to participate in the opinion of the Investigators will be excluded from the study: History of significant alcohol intake (Alcohol Use Disorders Identification Test [AUDIT]) or inability to quantify alcohol consumption Chronic use (more than 2 consecutive weeks) of medications known to cause hepatic steatosis or steatohepatitis in the past year. The use of other known hepatotoxins within 120 days of baseline History of total parenteral nutrition (TPN) use in the year prior to screening History of bariatric surgery or planning to undergo bariatric surgery during the study duration Significant depression Non-compensated liver disease with any one of the following hematologic, biochemical, and serological criteria on entry into protocol: Hemoglobin < 10 g/dL White blood cell < 3,500 cells/mm Neutrophil count < 1,500 cells/mm3 of blood Platelets < 130,000 cells/mm3 of blood Direct bilirubin > 1.0 mg/dL Total bilirubin > 3 mg/dL Albumin < 3.2 g/dL International normalized ratio (INR) > 1.4 Evidence of other chronic liver disease Children who are currently enrolled in a clinical trial or who received an investigational study drug or a medication with the intent to treat NAFLD/NASH in the past 60 days Contraindications to MRI, e.g. metal in the eyes, implanted electronic devices, aneurysm clips, pacemaker, cochlear implants Unable to have or complete the MRI exam due to body weight exceeding scanner table limit or girth exceeding scanner bore diameter Subjects who are not able or willing to comply with the protocol or have any other condition that would impede compliance or hinder completion of the study, in the opinion of the investigator Families with > 5 individuals Failure to give informed consent

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dietary modification<br>Low free sugar diet | Other: Dietary modification<br>* The intervention is a modification of the family's habitual diet with a low sugar version of their diet.<br>|
| No Intervention: Observational Arm<br>Standard of care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Percentage of Liver Fat Measured by Magnetic Resonance Imaging (MRI) in the Intervention Group Compared to Change in the Control Group | The principal objective of this randomized and controlled pilot study is to evaluate whether 8 weeks of a low added sugar diet (<3%) in boys with NAFLD will change liver fat % measured by MRI. | Measurements done at baseline and week 8. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alanine Aminotransferase (ALT) From Baseline to Week 8 |  | Measurements done at baseline and week 8 | 
| Change in Aspartate Aminotransferase (AST) From Baseline to Week 8 |  | Measurements doen at baseline and week 8 | 
| Change in Gamma-Glutamyl Transpeptidase (GGT) From Baseline to Week 8 |  | Measurements done at baseline and week 8 | 
| Change in Insulin From Baseline to Week 8 |  | Measurements done at baseline and week 8 | 
| Change in Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) From Baseline to Week 8 | HOMA-IR was calculated as follows: fasting insulin (µU/mL) x fasting glucose (nmol/L)/22.5 | Measurements done at baseline and week 8 | 
| Change in Triglycerides From Baseline to Week 8 |  | Measurements done at baseline and week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NAFLD, Steatohepatitis, Nonalcoholic Steatohepatitis (NASH), Liver, Diet, Pediatric, Adolescent