SMART Diets for MASLD

NCT07459504 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CHW-2026-12831R61HL174736-01A1
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metabolic-dysfunction Associated Steatotic Liver Disease

Keywords

MASLD; Adolescents; Liver; Sugar; Amino acid supplement

Outcome Measures

Primary Outcomes (1)

• Change in hepatic steatosis

  Change in hepatic steatosis by magnetic resonance imaging (MRI)

  Baseline to 24 weeks

Secondary Outcomes (15)

• Change in fasting triglyceride

  Baseline, 12 and 24 weeks

• Change in HDL

  Baseline, 12 and 24 weeks

• Change in VLDL-triglyceride

  Baseline, 12 and 24 weeks

• Change in Waist circumference

  Baseline, 12 and 24 weeks

• Change in body weight

  Baseline, 12 and 24 weeks

Study Arms (2)

Essential Amino Acids Supplementation

ACTIVE COMPARATOR

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

Low Sugar Diet

ACTIVE COMPARATOR

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

Interventions

Essential Amino Acids Supplementation intervention DRUG

EAA supplement contains the following formulation: histidine, isoleucine, leucine, lysine, phenylalanine, threonine, and valine

Also known as: EAA, AMS2392

Essential Amino Acids Supplementation

Low sugar diet OTHER

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.

Low Sugar Diet

Eligibility Criteria

• Age: 11 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Corewell Health West: collaborator
• Emory University: collaborator
• Michigan State University: lead

Study Sites (1)

Corewell Health West

Grand Rapids, Michigan, 49503, United States

RECRUITING

Study Officials

• Miriam B Vos, MD, MSPH

  Michigan State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Miriam B Vos, MD, MSPH

CONTACT

616-267-2100; miriam.vos@msu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Due to the nature of the treatment, it is not realistic to blind the treatment to either staff or patients and their caregivers. To mitigate the risk of bias associated with an unblinded study, all study team members will remain blinded to aggregate study results and only select members of the study team responsible for interim monitoring will have access to these data
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Sequential, multiple-assignment randomized trial

Study Record Dates

• First Submitted: February 17, 2026
• First Posted: March 9, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 26, 2029
• Study Completion (Estimated): December 26, 2030
• Last Updated: June 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• Access Criteria: The Emory DataVerse is an open-source web application available to registered users.

Locations

US (1)