Clinical trial NCT02513121: Dietary Treatment Study of Pediatric NAFLD
Official title: Randomized, Controlled Dietary Treatment Study of Pediatric NAFLD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nonalcoholic Fatty Liver Disease
Keywords: NAFLD
Steatohepatitis
Nonalcoholic Steatohepatitis (NASH)
Liver
Diet
Pediatric
Adolescent
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Emory University
name: Nutrition Science Initiative
First posted: 2015-07-31
Enrollment: 40
Sex: MALE
Minimum age (years): 11
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in Percentage of Liver Fat Measured by Magnetic Resonance Imaging (MRI) in the Intervention Group Compared to Change in the Control Group
timeFrame: Measurements done at baseline and week 8.
Secondary outcomes:
measure: Change in Alanine Aminotransferase (ALT) From Baseline to Week 8
timeFrame: Measurements done at baseline and week 8
measure: Change in Aspartate Aminotransferase (AST) From Baseline to Week 8
timeFrame: Measurements doen at baseline and week 8
measure: Change in Gamma-Glutamyl Transpeptidase (GGT) From Baseline to Week 8
timeFrame: Measurements done at baseline and week 8
measure: Change in Insulin From Baseline to Week 8
timeFrame: Measurements done at baseline and week 8
measure: Change in Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) From Baseline to Week 8
timeFrame: Measurements done at baseline and week 8
measure: Change in Triglycerides From Baseline to Week 8
timeFrame: Measurements done at baseline and week 8
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: University of California, San Diego
name: Jeffrey B Schwimmer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Miriam Vos, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.