Dietary Treatment Study of Pediatric NAFLD

NCT ID: NCT02513121

Last Updated: 2020-01-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2017-08-31

Brief Summary

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.

Conditions

Nonalcoholic Fatty Liver Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dietary modification

Low free sugar diet

Group Type: ACTIVE_COMPARATOR

Dietary modification

Intervention Type: OTHER

The intervention is a modification of the family's habitual diet with a low sugar version of their diet.

Observational Arm

Standard of care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Dietary modification

The intervention is a modification of the family's habitual diet with a low sugar version of their diet.

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 11 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: collaborator

Nutrition Science Initiative

OTHER

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey B. Schwimmer, MD

Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey B Schwimmer, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Miriam Vos, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

University of California, San Diego

San Diego, California, United States

Emory University

Atlanta, Georgia, United States

Countries

United States

References

Schwimmer JB, Deutsch R, Rauch JB, Behling C, Newbury R, Lavine JE. Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr. 2003 Oct;143(4):500-5. doi: 10.1067/S0022-3476(03)00325-1.

Reference Type: BACKGROUND

PMID: 14571229 (View on PubMed)

Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006 Oct;118(4):1388-93. doi: 10.1542/peds.2006-1212.

Reference Type: BACKGROUND

PMID: 17015527 (View on PubMed)

Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook S. Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation. 2008 Jul 15;118(3):277-83. doi: 10.1161/CIRCULATIONAHA.107.739920. Epub 2008 Jun 30.

Reference Type: BACKGROUND

PMID: 18591439 (View on PubMed)

Jin R, Le NA, Liu S, Farkas Epperson M, Ziegler TR, Welsh JA, Jones DP, McClain CJ, Vos MB. Children with NAFLD are more sensitive to the adverse metabolic effects of fructose beverages than children without NAFLD. J Clin Endocrinol Metab. 2012 Jul;97(7):E1088-98. doi: 10.1210/jc.2012-1370. Epub 2012 Apr 27.

Reference Type: BACKGROUND

PMID: 22544914 (View on PubMed)

Jin R, Welsh JA, Le NA, Holzberg J, Sharma P, Martin DR, Vos MB. Dietary fructose reduction improves markers of cardiovascular disease risk in Hispanic-American adolescents with NAFLD. Nutrients. 2014 Aug 8;6(8):3187-201. doi: 10.3390/nu6083187.

Reference Type: BACKGROUND

PMID: 25111123 (View on PubMed)

Schwimmer JB, Middleton MS, Behling C, Newton KP, Awai HI, Paiz MN, Lam J, Hooker JC, Hamilton G, Fontanesi J, Sirlin CB. Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease. Hepatology. 2015 Jun;61(6):1887-95. doi: 10.1002/hep.27666. Epub 2015 Feb 5.

Reference Type: BACKGROUND

PMID: 25529941 (View on PubMed)

Jin R, Vos MB. Fructose and liver function--is this behind nonalcoholic liver disease? Curr Opin Clin Nutr Metab Care. 2015 Sep;18(5):490-5. doi: 10.1097/MCO.0000000000000203.

Reference Type: BACKGROUND

PMID: 26203597 (View on PubMed)

Cohen CC, Li KW, Alazraki AL, Beysen C, Carrier CA, Cleeton RL, Dandan M, Figueroa J, Knight-Scott J, Knott CJ, Newton KP, Nyangau EM, Sirlin CB, Ugalde-Nicalo PA, Welsh JA, Hellerstein MK, Schwimmer JB, Vos MB. Dietary sugar restriction reduces hepatic de novo lipogenesis in adolescent boys with fatty liver disease. J Clin Invest. 2021 Dec 15;131(24):e150996. doi: 10.1172/JCI150996.

Reference Type: DERIVED

PMID: 34907907 (View on PubMed)

Schwimmer JB, Ugalde-Nicalo P, Welsh JA, Angeles JE, Cordero M, Harlow KE, Alazraki A, Durelle J, Knight-Scott J, Newton KP, Cleeton R, Knott C, Konomi J, Middleton MS, Travers C, Sirlin CB, Hernandez A, Sekkarie A, McCracken C, Vos MB. Effect of a Low Free Sugar Diet vs Usual Diet on Nonalcoholic Fatty Liver Disease in Adolescent Boys: A Randomized Clinical Trial. JAMA. 2019 Jan 22;321(3):256-265. doi: 10.1001/jama.2018.20579.

Reference Type: DERIVED

PMID: 30667502 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-4405

Identifier Type: -

Identifier Source: org_study_id