Clinical trial NCT05292352: Prevention of NAFLD in Hispanic Children
Official title: Prevention of Non-alcoholic Fatty Liver Disease (NAFLD) in Hispanic Children
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Non-Alcoholic Fatty Liver Disease
Keywords: Latino Children
Pre-puberal
Low Free sugar diet (LFSD)
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute of Nursing Research (NINR)
First posted: 2022-03-23
Enrollment: 300
Sex: ALL
Minimum age (years): 6
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: The number of children experiencing obesity and the chronic diseases associated with it have 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 with which they were born. Excess fat in the liver increases the risk of diabetes and heart disease as well the chance that a liver transplant will be needed. Previous studies suggest that diets high in sugar, particularly during critical periods of development, increases 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, reduces 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 increase in risk for NAFLD compared to non-Hispanic children has been well documented. Enrollment will include children age 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 is 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, incidence of NAFLD in the intervention group vs. control group will be assessed (primary outcome of 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Percent Hepatic Steatosis by MRI-PDFF
timeFrame: 12 month after start of intervention
measure: Onset of NAFLD
timeFrame: 24 months after start of intervention
Secondary outcomes:
measure: Changes in markers of liver inflammation: ALT
timeFrame: Baseline, month 6, month 12, month 18, and month 24
measure: Changes in markers of liver inflammation: AST
timeFrame: Baseline, month 6, month 12, month 18, and month 24
measure: Changes in markers of liver inflammation: GGT
timeFrame: Baseline, month 12 and month 24
measure: Changes in HbA1c
timeFrame: Baseline, month 12 and month 24
measure: Changes in fasting triglycerides
timeFrame: Baseline, Month 6, Month 12, month 18 and month 24
measure: Changes in Fasting insulin
timeFrame: Measured at baseline, month 12 and month 24
measure: Changes in HDL
timeFrame: Baseline, Month 6, Month 12, month 18 and month 24
measure: Changes in LDL
timeFrame: Baseline, Month 6, Month 12, month 18 and month 24
measure: Changes in waist hip ratio
timeFrame: Baseline, month 12 and month 24
measure: Changes in BMI
timeFrame: Baseline, month 12 and month 24
measure: Changes in Neck acanthosis nigricans
timeFrame: Baseline, month 12 and month 24
measure: Changes Oral Glucose tolerance test (OGTT)
timeFrame: Baseline, month 12 and month 24
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: Emory University
name: Miriam Vos, MD
role: PRINCIPAL_INVESTIGATOR
References: