Dietary Treatment Study of Pediatric NAFLD (DTS)

• ClinicalTrials.gov Identifier: NCT02513121
• Recruitment Status: Completed
• First Posted: July 31, 2015
• Results First Posted: January 28, 2020
• Last Update Posted: January 28, 2020
• Sponsor: University of California, San Diego
• Collaborators: Emory University; Nutrition Science Initiative
• Information provided by (Responsible Party): Jeffrey B. Schwimmer, MD, University of California, San Diego

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Nonalcoholic Fatty Liver Disease	Other: Dietary modification	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized, Controlled Dietary Treatment Study of Pediatric NAFLD
• Study Start Date: July 2015
• Actual Primary Completion Date: August 31, 2017
• Actual Study Completion Date: August 31, 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Dietary modification; Low free sugar diet	Other: Dietary modification; The intervention is a modification of the family's habitual diet with a low sugar version of their diet.
No Intervention: Observational Arm; Standard of care

Outcome Measures

Primary Outcome Measures :

1. Change in Percentage of Liver Fat Measured by Magnetic Resonance Imaging (MRI) in the Intervention Group Compared to Change in the Control Group [ Time Frame: Measurements done at baseline and week 8. ]
   The principal objective of this randomized and controlled pilot study is to evaluate whether 8 weeks of a low added sugar diet (<3%) in boys with NAFLD will change liver fat % measured by MRI.

Secondary Outcome Measures :

1. Change in Alanine Aminotransferase (ALT) From Baseline to Week 8 [ Time Frame: Measurements done at baseline and week 8 ]
2. Change in Aspartate Aminotransferase (AST) From Baseline to Week 8 [ Time Frame: Measurements doen at baseline and week 8 ]
3. Change in Gamma-Glutamyl Transpeptidase (GGT) From Baseline to Week 8 [ Time Frame: Measurements done at baseline and week 8 ]
4. Change in Insulin From Baseline to Week 8 [ Time Frame: Measurements done at baseline and week 8 ]
5. Change in Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) From Baseline to Week 8 [ Time Frame: Measurements done at baseline and week 8 ]
   HOMA-IR was calculated as follows: fasting insulin (µU/mL) x fasting glucose (nmol/L)/22.5
6. Change in Triglycerides From Baseline to Week 8 [ Time Frame: Measurements done at baseline and week 8 ]

Eligibility Criteria

• Ages Eligible for Study: 11 Years to 16 Years (Child)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

University of California, San Diego

San Diego, California, United States, 92093

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

Sponsors and Collaborators

University of California, San Diego

Emory University

Nutrition Science Initiative

Investigators

• Principal Investigator: Jeffrey B Schwimmer, MD; University of California, San Diego
• Principal Investigator: Miriam Vos, MD; Emory University

  Study Documents (Full-Text)

Documents provided by Jeffrey B. Schwimmer, MD, University of California, San Diego:

Study Protocol  [PDF] February 10, 2016

Statistical Analysis Plan  [PDF] February 10, 2016

More Information

Publications:

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.

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.

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.

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.

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.

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.

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. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Erratum in: JAMA. 2019 Aug 6;322(5):469.

• Responsible Party: Jeffrey B. Schwimmer, MD, Professor of Pediatrics, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT02513121
• Other Study ID Numbers: 2015-4405
• First Posted: July 31, 2015
• Results First Posted: January 28, 2020
• Last Update Posted: January 28, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified participant data will be made available in response to bona fide and good faith, ad hoc requests. Suitability of each request, if consistent with Institutional Review Board (IRB) approval, will be determined only in the case of a favorable vote of a majority of a committee consisting of each consortium investigator and the Grantor. Data will be made available with a signed access agreement.

Keywords provided by Jeffrey B. Schwimmer, MD, University of California, San Diego:

NAFLD; Steatohepatitis; Nonalcoholic Steatohepatitis (NASH); Liver; Diet; Pediatric; Adolescent

Additional relevant MeSH terms:

Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Digestive System Diseases