SMART Diets for MASLD

A Sequential Multiple Assignment Randomized Trial of Diet Treatments for Hepatic Steatosis and Cardiometabolic Risk in Youth

This phase 2 trial is a single-site sequential, multiple assignment, randomized trial (SMART) to test and construct a high-quality adaptive intervention of essential amino acids (EAA) and/or Low Sugar Diet for children with metabolic dysfunction associated steatotic liver disease (MASLD) and increased cardiometabolic risk. The basis for the trial includes high-quality pilot data in both EAA for hepatic steatosis and a low sugar diet for hepatic steatosis. In the trial, children aged 11-17 years old will be eligible to participate if their BMI is greater than or equal to 95th% at baseline and hepatic steatosis is greater than or equal to 8% at baseline by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) because this is the most common age group diagnosed with metabolic-dysfunction associated steatotic liver disease.

Study Overview

• Status: Recruiting
• Conditions: Metabolic-dysfunction Associated Steatotic Liver Disease
• Intervention / Treatment: Drug: Essential Amino Acids Supplementation intervention; Other: Low sugar diet

Detailed Description

Metabolic-dysfunction associated steatotic liver disease is defined as the presence of abnormal hepatic stored triglycerides (hepatic steatosis), with one or more of 5 cardiometabolic factors (increased body mass index or waist circumference, hyperglycemia, hypertriglyceridemia, or low HDL) and no other chronic liver disease. Pediatric hepatic steatosis is central to long-term metabolic and cardiovascular health because of the relation of hepatic steatosis to the development of other major diseases. Hepatic steatosis limits the normal metabolic role of insulin and plays a key role in the future development of the metabolic syndrome, and is the strongest predictor for the development of type 2 diabetes.

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Miriam B Vos, MD, MSPH; Phone Number: 616-267-2100; Email: miriam.vos@msu.edu

Study Locations

• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • Corewell Health West
      • Principal Investigator: Miriam B Vos, MD, MSPH
      • Contact: Renee Stuller, RN; Phone Number: 616-391-2460; Email: renee.stuller@corewellhealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children 11 to 17-years-old at the time of consenting
• Hepatic Steatosis by MRI greater than or equal to 8% on baseline MRI
• At least 1 of the following cardiometabolic risk factors: BMI greater than or equal to 85th percentile for age/sex or WC greater than 95th percentile, Abnormal cholesterol or triglyceride levels, Blood pressure BP greater than or equal to 95th percentile OR greater than or equal to 130/80 and/or signs of insulin resistance (Acanthosis Nigricans OR HOMA-IR of greater 2.0 and greater 2.6 in prepubertal and pubertal children, respectively, Fasting Insulin Level of 10 pIU/mL in prepubertal children and of 17 pIU/mL and 13 pIU/mL in pubertal girls and boys, respectively, OR Prediabetes)
• ALT greater than or equal to 40 U/L
• Currently consumes greater than or equal to 2 eight-ounce sugar drinks (or juice) per week.
• Patients of childbearing potential agrees to use adequate one or more effective methods of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
• Patients who are taking medications that can affect insulin (e.g., metformin, corticosteroids), most be on a stable dosage for at least 3 months prior to enrollment of the trial.
• Written informed consent from parent or legal guardian, assent from child.

Exclusion Criteria:

• Patients with Diagnosed Type 2 or Type 1 Diabetes Mellitus (T2DM) or HbA1c of >6.5 mg/dL at baseline
• Patients diagnosed with or suspected to have a chronic liver disease other than MASLD by screening labs or evaluation (i.e autoimmune, viral). Screening labs are defined as: Hepatitis B surface antigen, Hepatitis C virus total antibody, IgG, ceruloplasmin, and alpha 1 antitrypsin phenotype.
• Patients unable to complete MRI or Labs required for the study.
• Current participation in another clinical trial
• Current participation in a weight loss program or obesity treatment program or clinic
• Cancer or history of cancer within 5 years
• Severe illness that required hospitalization in the last 60 days
• Use of medications known to cause liver steatosis (TPN, amiodarone, chronic oral steroids, etc.)
• Patients with implanted metal devices that are not compatible with magnetic resonance imaging (MRI).
• Intellectual disability or major psychiatric disorder limiting informed assent
• Clinical evidence of cirrhosis or advanced liver disease by any one of the following abnormal labs: (Hemoglobin less than 10 g/dL, White blood cell less than 3,500 cells/mm, Neutrophil count less than 1,500 cells/mm3 of blood, Platelets less than 130,000 cells/mm3 of blood, Direct bilirubin greater than 1.0 mg/dL)
• Elevated total bilirubin except if known to have Gilbert's syndrome and direct bilirubin in normal range.
• Albumin less than 3.2 g/dL
• A history of international normalized ratio (INR) greater than 1.4
• AST or ALT greater than 250 IU/dL.
• Compensated or decompensated cirrhosis with evidence of portal hypertension.
• Patients is pregnant or breastfeeding.
• Patients who have been enrolled in a recent clinical trial and had the last dose of investigational product within 30 days or 5 half-lives of the study drug, whichever is longer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Essential Amino Acids Supplementation; The essential amino acid supplement contains the following formulation: histidine, isoleucine, leucine, lysine, phenylalanine, threonine, and valine. EAA, also called AMS2392 has been shown to decrease hepatic steatosis and lower circulating very-low-density lipoprotein triglyceride (VLDL-TG) concentrations through one or more of the following mechanisms: decreasing de novo lipogenesis; increasing hepatic and systemic fatty acid oxidation; increasing triglyceride secretion from the liver in the form of VLDL-TG; and increasing clearance of circulating VLDL-TG via activation of lipoprotein lipase.	Drug: Essential Amino Acids Supplementation intervention; EAA supplement contains the following formulation: histidine, isoleucine, leucine, lysine, phenylalanine, threonine, and valine; Other Names: EAA; AMS2392
Active Comparator: Low Sugar Diet; The Low Sugar Diet uses the adapted and extended Social Cognitive Theory (SCT) guided low sugar intervention that the Emory team previously developed. The registered dietitian nutritionist (RDN) helps families to identify foods high in sugar and to identify acceptable replacements in order to remove foods and drinks high in free sugar from the home and replacement with low or no free sugar containing similar foods.	Other: Low sugar diet; The Low Sugar Diet uses the adapted and extended Social Cognitive Theory (SCT) guided low sugar intervention. The registered dietitian nutritionist (RDN) helps families to identify foods high in sugar and to identify acceptable replacements in order to remove foods and drinks high in free sugar from the home and replacement with low or no free sugar containing similar foods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hepatic steatosis	Change in hepatic steatosis by magnetic resonance imaging (MRI)	Baseline to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fasting triglyceride	Change in triglyceride in mg/dL	Baseline, 12 and 24 weeks
Change in HDL	Change in HDL mg/dL	Baseline, 12 and 24 weeks
Change in VLDL-triglyceride	Very-low-density-lipoprotein triglyceride	Baseline, 12 and 24 weeks
Change in Waist circumference	Change in Waist circumference in cm	Baseline, 12 and 24 weeks
Change in body weight	Change in weight in kilograms	Baseline, 12 and 24 weeks
Change in BMI Z Score	Change in body mass index z-score	Baseline, 12 and 24 weeks
Change in Alanine Aminotransferase (ALT)	Change in ALT	Baseline, 12 and 24 weeks
Aspartate Aminotransferase (AST)	Change in AST	Baseline, 12 and 24 weeks
Gamma glutamyl transferase (GGT)	Change in GGT	Baseline, 12 and 24 weeks
Systolic blood pressure	Change in systolic blood pressure mg/dL	Baseline, 12 and 24 weeks
Diastolic blood pressure	Change in diastolic blood pressure (mg/dL)	Baseline, 12 and 24 weeks
Hemoglobin A1c	Change in hemoglobin A1c	Baseline, 12 and 24 weeks
HOMA-IR	Change in homeostatic model assessment of insulin resistance (HOMA-IR)	Baseline, 12 and 24 weeks
Adverse events	Number of adverse events compared between arms of the study	Baseline, 12 and 24 weeks
Percent responders	Percent of participants who reduce hepatic steatosis in the group that start with low sugar diet compared to the group that starts with EAA intervention	Baseline to 24 weeks

Collaborators and Investigators

• Sponsor: Michigan State University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Emory University; Corewell Health West
• Investigators: Principal Investigator: Miriam B Vos, MD, MSPH, Michigan State University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 26, 2029
• Study Completion (Estimated): December 26, 2030

Study Registration Dates

• First Submitted: February 17, 2026
• First Submitted That Met QC Criteria: March 5, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Adolescents; Amino acid supplement; Liver; Sugar; MASLD
• Other Study ID Numbers: CHW-2026-1283; 1R61HL174736-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The proposed research will include data from approximately 102 participants at up to 3 time-points. The final scientific datasets will include intervention assignment, anthropometrics, laboratory and imaging data. All protected health information and personally identified information will be removed. The study dates will be removed. Scientific data from the primary and secondary endpoints, along with a detailed data dictionary, and study protocols will be made available on a data repository such as Emory DataVerse. Genetic information for participants will not be made available.
• IPD Sharing Time Frame: The IPD will be available within one year of the publication of the results of the trial and will be hosted for at least 2 years.
• IPD Sharing Access Criteria: The Emory DataVerse is an open-source web application available to registered users.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No