Non-Alcoholic Fatty Liver Disease
Conditions
Keywords
Latino Children, Pre-puberal, Low Free sugar diet (LFSD)
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 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.
Interventions
BEHAVIORALLFSD
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.
Sponsors
Emory University
National Institute of Nursing Research (NINR)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 9 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percent Hepatic Steatosis by by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) | 12 month after start of intervention | The primary objective for the 12-month study is to test if an LFSD, compared to usual diet protects against increase in hepatic steatosis |
| Onset of NAFLD | up to 24 months after start of intervention | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Markers of liver inflammation: Alanine Transaminase (ALT) | Baseline, month 6, month 12, month 18, and month 24 | ALT will be measured from comprehensive metabolic panel (CMP) lab test and compared |
| Markers of liver inflammation: aspartate aminotransferase (AST) | Baseline, month 6, month 12, month 18, and month 24 | AST will be measured from CMP lab test and compared |
| Markers of liver inflammation: gamma-glutamyltransferase (GGT) | Baseline, month 12 and month 24 | Laboratory tests will be collected and values compared |
| Changes in HbA1c | Baseline, month 12 and month 24 | 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. |
| Changes in fasting triglycerides | Baseline, Month 6, Month 12, month 18 and month 24 | 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. |
| Changes in Fasting insulin | Measured at baseline, month 12 and month 24 | Measured before the OGTT study |
| Changes in HDL | Baseline, Month 6, Month 12, month 18 and month 24 | 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. |
| Changes in LDL | Baseline, Month 6, Month 12, month 18 and month 24 | 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. |
| Changes in waist hip ratio | Baseline, month 12 and month 24 | BMI will be calculated from weight and height measured twice and averaged. Waist and hip measurements will be performed. |
| Changes in BMI | Baseline, month 12 and month 24 | BMI and BMI percentile will be calculated from weight and height measured twice and averaged. |
| Changes in Neck acanthosis nigricans | Baseline, month 12 and month 24 | 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. |
| Changes Oral Glucose tolerance test (OGTT) | Baseline, month 12 and month 24 | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJean Welsh, PhD, MPH, RN
Emory University
Outcome results
None listed