LFSD for Preventing Fatty Liver Disease in Children

Overseen By Miriam Vos, MD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Emory University

Must not be taking: TPN, Amiodarone, Oral steroids

Disqualifiers: Chronic liver disease, Type 2 diabetes, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 18

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if reducing dietary sugars can help prevent non-alcoholic fatty liver disease (NAFLD) in children. The study will compare two groups: one will follow a low free sugar diet (LFSD) guided by a behavior change framework, while the other will receive usual care with healthy lifestyle tips. The trial seeks Hispanic children between the ages of 6 and 9 with a body mass index (BMI) at or above the 50th percentile. Participants must not have any chronic liver disease other than NAFLD and should not have participated in a weight loss program.

As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could improve children's health.

Will I have to stop taking my current medications?

The trial does not specify if participants must stop taking their current medications. However, if you are using medications known to cause fatty liver, you may not be eligible to participate.

What prior data suggests that the LFSD intervention is safe for children?

Research has shown that a Low Free Sugar Diet (LFSD) is generally safe for children. One study found that reducing free sugars can lower liver fat in kids, aiding conditions like non-alcoholic fatty liver disease (NAFLD). Specifically, children on this diet did not experience major negative side effects. Instead, the diet appears to enhance liver health without causing harm. While additional research is beneficial, current findings positively support the safety of LFSD for young participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Low Free Sugar Diet (LFSD) for preventing fatty liver disease in children because, unlike standard treatments that might focus on medication or more generalized dietary advice, LFSD uses a targeted approach to reduce sugar intake based on Social Cognitive Theory. This method empowers children and their families to make lasting lifestyle changes by understanding and controlling their behavior to achieve their health goals. By focusing specifically on reducing free sugars in the diet, LFSD offers a potentially sustainable and natural way to prevent fatty liver disease, which is particularly appealing for young patients.

What evidence suggests that the LFSD intervention could be effective for preventing fatty liver disease in children?

Research has shown that a diet low in free sugars can help reduce liver fat in children with non-alcoholic fatty liver disease (NAFLD). In one study, boys on a low-sugar diet experienced an average 31% drop in liver fat. This trial will test the Low Free Sugar Diet (LFSD) intervention, which focuses on reducing sugars added to foods and drinks, as well as those naturally found in honey, syrups, and fruit juices. By cutting these sugars, the diet aims to prevent excessive fat storage in the liver. Eating less sugar may lead to less fat buildup in the liver, helping to manage and prevent NAFLD. ^{1 2 5 6 7}

Who Is on the Research Team?

Miriam Vos, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for pre-pubertal Hispanic children aged 6-9 with a BMI ≥ 50th percentile, normal liver enzymes, and no significant health issues like cancer or chronic liver diseases other than NAFLD. They must not be on certain medications, planning to move soon, or have conditions that prevent MRI scans.

Inclusion Criteria

At least one parent or the child self-identifies as Hispanic or Latino

Normal ALT on screening labs (≤23 IU for girls, ≤26 IU for boys)

Written informed consent from parent or legal guardian, assent from child

Exclusion Criteria

I have been part of a weight loss or obesity treatment program.

Children who spend more than 1 night per week consistently in another household

I have a history of severe depression.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow a 1-year dietary intervention to reduce dietary sugars, including dietary counseling and guided grocery shopping

12 months

Monthly visits for assessments and counseling

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of liver fat and metabolic health

12 months

Visits at month 18 and month 24

Long-term follow-up

Assessment of NAFLD incidence and other health markers at 24 months

24 months

What Are the Treatments Tested in This Trial?

Interventions

• LFSD

Trial Overview The study tests an intensive diet intervention focused on reducing dietary sugars to prevent non-alcoholic fatty liver disease (NAFLD) in children. It's a two-year trial where the effectiveness of this Low Free Sugar Diet (LFSD) will be monitored.

How Is the Trial Designed?

Group I: Low Free Sugar Diet (LFSD) Intervention Experimental Treatment 1 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.

Group II: Usual Care Control Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Institute of Nursing Research (NINR)

Collaborator

Trials

623

Recruited

10,400,000+

Published Research Related to This Trial

A systematic review of 21 randomized controlled trials involving 1307 children with nonalcoholic fatty liver disease (NAFLD) revealed significant heterogeneity in study designs and endpoints, with only 38% of trials using biopsy-proven NAFLD as an inclusion criterion.

While lifestyle interventions, polyunsaturated fatty acids (PUFAs), and antioxidants showed some benefits in reducing biomarkers of NAFLD, few studies included histologic analyses to validate these effects, indicating a need for more standardized outcome measures in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluations of Lifestyle, Dietary, and Pharmacologic Treatments for Pediatric Nonalcoholic Fatty Liver Disease: A Systematic Review. Mann, JP., Tang, GY., Nobili, V., et al.[2020]

This study will investigate whether a low-free sugar diet (LFSD) can prevent liver fat accumulation in 140 Hispanic children aged 6 to 9 years who are at risk for non-alcoholic fatty liver disease (NAFLD).

The primary outcomes will measure changes in liver fat percentage and the incidence of significant liver fat and elevated liver enzymes after 12 and 24 months, potentially providing insights for future dietary guidelines to prevent NAFLD in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for a randomized, controlled trial using a novel, family-centered diet treatment to prevent nonalcoholic fatty liver disease in Hispanic children. Welsh, JA., Pyo, E., Huneault, H., et al.[2023]

In a study of 66 children with non-alcoholic fatty liver disease (NAFLD) followed for up to 20 years, a significant number (83%) presented with features of metabolic syndrome, indicating a strong link between NAFLD and metabolic health issues.

The long-term prognosis for these children is concerning, as they showed a much shorter survival rate compared to the general population, with some requiring liver transplantation due to progression to end-stage liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Feldstein, AE., Charatcharoenwitthaya, P., Treeprasertsuk, S., et al.[2022]

In a randomized controlled trial involving 169 children with nonalcoholic fatty liver disease (NAFLD), cysteamine bitartrate delayed release (CBDR) did not significantly improve overall liver histology compared to placebo after 52 weeks.

However, CBDR treatment led to significant reductions in liver enzymes (alanine aminotransferase and aspartate aminotransferase) and a higher percentage of children showed reduced lobular inflammation, particularly in those weighing 65 kg or less, where the chance of histologic improvement was four times greater compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores. Schwimmer, JB., Lavine, JE., Wilson, LA., et al.[2019]

In a study of 36 obese children and adolescents, 66.7% were found to have non-alcoholic fatty liver disease (NAFLD), with varying degrees of severity, indicating a high prevalence of this condition in this population.

A 12-month lifestyle intervention focusing on increased physical activity led to significant improvements, with 37.5% of participants experiencing resolution of NAFLD and reductions in BMI, insulin resistance, and liver enzyme levels, highlighting the effectiveness of weight loss in treating NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Non-alcoholic fatty liver disease and its association with clinical and biochemical variables in obese children and adolescents: effect of a one-year intervention on lifestyle]. Santomauro, M., Paoli-Valeri, M., Fernández, M., et al.[2014]

In a study of 26 obese children with non-alcoholic fatty liver disease (NAFLD), weight reduction was linked to significant decreases in liver fat and stiffness, indicating improved liver health.

Short-term weight management through hospital admission was more effective than self-directed weight loss over a longer period, leading to greater reductions in both weight and liver-related parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of obesity reduction on transient elastography-based parameters in pediatric non-alcoholic fatty liver disease. Isoura, Y., Cho, Y., Fujimoto, H., et al.[2021]

Nonalcoholic fatty liver disease (NAFLD) is a significant health issue affecting up to 70% of obese children and is the leading cause of liver transplants in the U.S.

Current treatment strategies often fail to prevent NAFLD progression in children through lifestyle changes alone, highlighting the urgent need for including children in pharmacological trials for NAFLD, which have primarily focused on adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical need for pharmacologic treatment options in NAFLD: A pediatric perspective. Friesen, CS., Chan, SS., Wagner, JB., et al.[2022]

A multidisciplinary clinical program for children with nonalcoholic fatty liver disease (NAFLD) led to significant improvements in weight-related outcomes, including a decrease in BMI z score and liver enzyme levels after one year.

Out of 108 enrolled children, 39 showed notable reductions in cholesterol and liver enzymes, indicating that structured dietary and exercise advice can effectively manage NAFLD in a gastroenterology setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multidisciplinary clinical program is effective in stabilizing BMI and reducing transaminase levels in pediatric patients with NAFLD. DeVore, S., Kohli, R., Lake, K., et al.[2021]

A systematic review of six randomized controlled trials involving 378 children with nonalcoholic fatty liver disease (NAFLD) found that omega-3 fatty acids significantly reduced liver enzyme levels and improved liver fat as seen on ultrasound.

Supplementation with omega-3 fatty acids also led to a decrease in Body Mass Index (BMI), suggesting it may be an effective alternative treatment for pediatric NAFLD, although more research is needed on its effects on liver tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can omega-3 fatty acids be beneficial in pediatric NAFLD? A systematic review and meta-analysis. Dionysopoulos, G., Kalopitas, G., Vadarlis, A., et al.[2023]

In a 24-month observational study involving 57 overweight or obese children with nonalcoholic fatty liver disease (NAFLD), metformin combined with lifestyle interventions did not show greater effectiveness than lifestyle changes alone in improving liver enzyme levels and histology.

Both the metformin group and the control group experienced significant improvements in liver enzymes and liver histology, indicating that lifestyle modifications are crucial in managing NAFLD in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin use in children with nonalcoholic fatty liver disease: an open-label, 24-month, observational pilot study. Nobili, V., Manco, M., Ciampalini, P., et al.[2013]

In a study of 784 children, it was found that the class of obesity (I, II, or III) is a better predictor of abnormal alanine aminotransferase (ALT) levels, which indicate a risk for non-alcoholic fatty liver disease (NAFLD), than the child's age.

Specifically, children with class II and III obesity had significantly higher odds of abnormal ALT levels (2.1-fold and 4-fold greater, respectively) compared to those with class I obesity, highlighting the importance of obesity classification in screening for NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stratification by obesity class, rather than age, can identify a higher percent of children at risk for non-alcoholic fatty liver disease and metabolic dysfunction. Radulescu, A., Dugan, AJ., Killian, M., et al.[2023]

In a study of 76 overweight/obese children with nonalcoholic fatty liver disease (NAFLD), omega-3 fatty acid supplementation did not significantly reduce alanine aminotransferase (ALT) levels compared to placebo after 6 months.

However, omega-3 supplementation did lead to lower levels of aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT), suggesting some improvement in liver function despite no change in overall liver steatosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 Fatty acids therapy in children with nonalcoholic Fatty liver disease: a randomized controlled trial. Janczyk, W., Lebensztejn, D., Wierzbicka-Rucińska, A., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6440226/

Effect of a Low Free Sugar Diet vs Usual Diet on ... ... children with nonalcoholic fatty liver disease ... liver fat content on MRI with histologic response in nonalcoholic steatohepatitis.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10734403/

Study Protocol for a Randomized, Controlled Trial Using a ... Nonalcoholic fatty liver disease (NAFLD) refers to a spectrum of liver diseases from fatty liver (steatosis) and inflammation (steatohepatitis) to end-stage ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0022316622006587

Clinical Intervention to Reduce Dietary Sugar Does Not ... The prevalence of pediatric nonalcoholic fatty liver disease (NAFLD) has doubled over the past 20 y (1). This is concerning given that NAFLD is a risk factor ...

4. health.ucsd.edu health.ucsd.edu/news/press-releases/2019-01-22-study-shows-low-sugar-diet-effective-in-boys-with-nafld/

Study Shows Low-Sugar Diet Effective in Boys with ... Study Shows Low-Sugar Diet Effective in Boys with Nonalcoholic Fatty Liver Disease. Diet revealed 31 percent reduction in liver fat on average.

5. withpower.com withpower.com/trial/phase-liver-diseases-3-2022-c531b

LFSD for Preventing Fatty Liver Disease in Children ... LFSD will have tolerable side effects & efficacy for patients with Nonalcoholic Steatohepatitis and Non-alcoholic Fatty Liver Disease. Learn more about the

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1551714423000939

Study protocol for a randomized, controlled trial using a ... This study aims to determine if a low-free sugar diet (LFSD) can prevent liver fat accumulation and NAFLD in high-risk children.

7. mdpi.com mdpi.com/1648-9144/57/7/719

Non-Alcoholic Fatty Liver Disease in Children NAFLD encompasses a wide spectrum of manifestations, from isolated hepatic steatosis without inflammation, to advanced form non-alcoholic steatohepatitis (NASH) ...