Prevention of NAFLD in Hispanic Children

Prevention of Non-alcoholic Fatty Liver Disease (NAFLD) in Hispanic Children

This is a 2 year clinical trial testing an intensive intervention to reduce dietary sugars as a means to prevent non-alcoholic fatty liver disease (NAFLD) in pre-pubertal Hispanic children.

Study Overview

• Status: Terminated
• Conditions: Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Behavioral: LFSD

Detailed Description

The number of children experiencing obesity and the chronic diseases associated with it has risen dramatically in recent decades. This includes non-alcoholic fatty liver disease (NAFLD). NAFLD is an excess accumulation of fat in the liver that results when children's diet and activity patterns compound the genetic risk they were born with. Excess fat in the liver increases the risk of diabetes and heart disease, as well as the chance that a liver transplant will be needed. Previous studies suggest that diets high in sugar, particularly during critical periods of development, increase children's risk of developing NAFLD. The study team has previously shown that reducing intake of free sugars (those used to sweeten foods and beverages and those found naturally in fruit juices) to very low levels reduce the amount of fat stored in the liver and improves the metabolic health of children with NAFLD.

This single-site randomized clinical trial is designed to determine if following a diet very low in free sugars just before puberty, a time of increased metabolic disruption, can help to prevent NAFLD in children known to be at high risk. This trial will study free-living Hispanic children with overweight or obesity because their increased risk for NAFLD compared to non-Hispanic children has been well documented. Enrollment will include children ages 6-9 years and Tanner stage 1 living in the Atlanta metropolitan area. Recruitment is through local pediatric clinics and through parents attending diabetes and NAFLD clinics. Enrollment and informed consent are performed by members of the research team. The one-year dietary intervention will include a combination of evidence-based strategies: dietary counseling by a nutritionist using motivational interviewing and family-centered goal setting; a one-month provision of a low/free sugar diet for the entire family, and nutritionist-guided (and study-funded) grocery shopping trips every 3 months thereafter. The control group will follow their usual diet and receive similar study assessments and compensation.

The primary outcome at year one is MRI-assessed change in the amount of liver fat from baseline. At 24 months, the incidence of NAFLD in the intervention group vs. the control group will be assessed (primary outcome of the 24-month study). Other outcomes to be assessed at 12- and 24-months include changes in liver enzymes, glucose metabolism, dyslipidemia, body composition, and metabolomics.

These studies may inform the development of guidelines for clinicians, dietitians, parents, and others involved in counseling and caring for children at high risk of developing NAFLD.

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 9 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. At least one parent or the child self-identifies as Hispanic or Latino.
2. BMI ≥ 50th percentile for age and sex.
3. Age ≥ 6 years and ≤ 9 years
4. Tanner stage 1 by self and/or parental report
5. Normal ALT on screening labs (≤23 IU for girls, ≤26 IU for boys)
6. Written informed consent from parent or legal guardian, assent from child

Exclusion Criteria:

1. Known diagnosis of chronic liver disease other than NAFLD and "fatty liver"
2. History of significant depression
3. Implanted metal or other implant (braces ok), or claustrophobia or other reason that contraindicates MRI
4. Type 2 diabetes (Hemoglobin A1c > 6.4% on screening labs or chronic diagnosis)
5. Plans to move within the next 12 months
6. Current or previous participation in a weight loss program or obesity treatment program or clinic
7. Cancer or history of cancer
8. Recipient of a liver transplant
9. Chronic use (in the last year) of medications known to cause NAFLD or fatty liver (TPN, amiodarone, chronic oral steroids, etc.)
10. Intellectual disability or major psychiatric disorder limiting informed assent
11. At risk for eating disorder by screening instrument
12. Participants who are currently enrolled in a clinical trial or have received an investigational product within the last 60 days
13. Participants who are not able or willing to comply with the diet protocol or have any other condition or circumstance that would impede compliance or hinder completion of the study in the opinion of the investigator
14. Children who spend more than 1 night per week consistently in another household

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Free Sugar Diet (LFSD) Intervention; The 1-year dietary intervention will be accomplished by adapting and extending a Social Cognitive Theory (SCT) guided low sugar intervention. SCT is a framework that helps explain how people regulate their behavior through control and reinforcement to achieve goal-directed behavior that can be maintained over time.	Behavioral: LFSD; Assessment of child's usual diet to assess sugar intake in relation to the total usual diet. Consultation with a nutritionist to help families identify foods high in sugar. Removal of foods and drinks high in free sugar from the home. Counseling using motivational interviewing, patient-centered goal setting to help parents and participating youth identify barriers to compliance with the intervention. Provision of a study provided LFSD with sufficient quantity to meet the needs and adapted to meet the preferences of the entire household for the first 4 weeks. Facilitated grocery shopping trips every 3 months during year 1.
No Intervention: Usual Care Control; Usual Care (Control group): Parents of enrolled children in the usual care group will be provided printed material on healthy family lifestyle at the beginning of the study. The control group will complete all of the same research visits and assessments as the intervention group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Percent Hepatic Steatosis by by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)	The primary objective for the 12-month study is to test if an LFSD, compared to usual diet protects against increase in hepatic steatosis	12 month after start of intervention
Onset of NAFLD	The primary objective for the 24-month is to study to test if an LFSD protects against development of NAFLD (hepatic steatosis ≥ 5% and elevated ALT).	up to 24 months after start of intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in HbA1c	Changes in HbA1c will be reviewed by a physician study investigator for patient safety. If patients develop clinically relevant abnormalities, the results will be provided to the pediatrician of the child or other provider as directed by the parents/guardians.	Baseline, month 12 and month 24
Changes in Fasting insulin	Measured before the OGTT study	Measured at baseline, month 12 and month 24
Changes in HDL	Fasting lipid panels will be performed at each visit. Frozen plasma will be shipped to LabCorp for NMR lipoprotein particle size measurement, extended lipid profiles and GlycA measurement.	Baseline, Month 6, Month 12, month 18 and month 24
Changes in LDL	Fasting lipid panels will be performed at each visit. Frozen plasma will be shipped to LabCorp for NMR lipoprotein particle size measurement, extended lipid profiles and GlycA measurement.	Baseline, Month 6, Month 12, month 18 and month 24
Changes in BMI	BMI and BMI percentile will be calculated from weight and height measured twice and averaged.	Baseline, month 12 and month 24
Changes in Neck acanthosis nigricans	Acanthosis nigricans (AN) monitoring: To improve objective assessment, AN will be captured using a photo of the neck base and by standardized assessment (scale 0 to 4) by the study coordinator or the investigator. Will be assessed by the "Neck Acanthosis Severity Scale" that ranges from 0-4.	Baseline, month 12 and month 24
Markers of liver inflammation: Alanine Transaminase (ALT)	ALT will be measured from comprehensive metabolic panel (CMP) lab test and compared	Baseline, month 6, month 12, month 18, and month 24
Markers of liver inflammation: aspartate aminotransferase (AST)	AST will be measured from CMP lab test and compared	Baseline, month 6, month 12, month 18, and month 24
Markers of liver inflammation: gamma-glutamyltransferase (GGT)	Laboratory tests will be collected and values compared	Baseline, month 12 and month 24
Changes in fasting triglycerides	Fasting lipid panels will be performed at each visit. Frozen plasma will be shipped to LabCorp for NMR lipoprotein particle size measurement, extended lipid profiles, and GlycA measurement.	Baseline, Month 6, Month 12, month 18 and month 24
Changes in waist hip ratio	BMI will be calculated from weight and height measured twice and averaged. Waist and hip measurements will be performed.	Baseline, month 12 and month 24
Changes Oral Glucose tolerance test (OGTT)	An oral glucose tolerance test (OGTT) will be performed for measures of adipose and peripheral IR. After the IV is placed, the fasting labs will be drawn from it. For the OGTT, we will perform frequent sampling of glucose and insulin and store blood for additional assays such as free fatty acid (FFA )and C-peptide. Bloods will be drawn using an 8-sample schedule after consumption of the glucose beverage (0, 10, 20, 30, 60, 90, 120, and 180 min). The OGTT beverage will consist of 50 g plus an additional 40 mg/kg of glucose. Whole body insulin sensitivity (Si) will be calculated with a 4-hour oral minimal model, utilizing SAM II software137. Adipose IR will be calculated as the FFA nadir, as in our preliminary data.	Baseline, month 12 and month 24

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Institute of Nursing Research (NINR)
• Investigators: Principal Investigator: Jean Welsh, PhD, MPH, RN, Emory University

Publications and helpful links

General Publications

• Welsh JA, Pyo E, Huneault H, Gonzalez Ramirez L, Alazraki A, Alli R, Dunbar SB, Khanna G, Knight-Scott J, Pimentel A, Reed B, Rodney-Somersall C, Santoro N, Umpierrez G, Vos MB. Study protocol for a randomized, controlled trial using a novel, family-centered diet treatment to prevent nonalcoholic fatty liver disease in Hispanic children. Contemp Clin Trials. 2023 Jun;129:107170. doi: 10.1016/j.cct.2023.107170. Epub 2023 Apr 3.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2022
• Primary Completion (Actual): March 31, 2026
• Study Completion (Actual): March 31, 2026

Study Registration Dates

• First Submitted: March 15, 2022
• First Submitted That Met QC Criteria: March 15, 2022
• First Posted (Actual): March 23, 2022

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Latino Children; Pre-puberal; Low Free sugar diet (LFSD)
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: STUDY00002076; 1R01NR019083-01A1 (U.S. NIH Grant/Contract); 2025P010571 (Other Identifier: Emory Insight Humans IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data underlying published findings
• IPD Sharing Time Frame: Data will be made available 6 months after publication. Applications must be submitted within 24 months of publication date.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal, to achieve aims in an approved proposal. Access will be granted by submitting written detailed proposal to the corresponding author of the published article.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No