SMART Diets for MASLD

May 28, 2026 updated by: Miriam B. Vos, Michigan State University

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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
102

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • Corewell Health West
        • Principal Investigator:
          • Miriam B Vos, MD, MSPH
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in hepatic steatosis
Time Frame: Baseline to 24 weeks
Change in hepatic steatosis by magnetic resonance imaging (MRI)
Baseline to 24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in fasting triglyceride
Time Frame: Baseline, 12 and 24 weeks
Change in triglyceride in mg/dL
Baseline, 12 and 24 weeks
Change in HDL
Time Frame: Baseline, 12 and 24 weeks
Change in HDL mg/dL
Baseline, 12 and 24 weeks
Change in VLDL-triglyceride
Time Frame: Baseline, 12 and 24 weeks
Very-low-density-lipoprotein triglyceride
Baseline, 12 and 24 weeks
Change in Waist circumference
Time Frame: Baseline, 12 and 24 weeks
Change in Waist circumference in cm
Baseline, 12 and 24 weeks
Change in body weight
Time Frame: Baseline, 12 and 24 weeks
Change in weight in kilograms
Baseline, 12 and 24 weeks
Change in BMI Z Score
Time Frame: Baseline, 12 and 24 weeks
Change in body mass index z-score
Baseline, 12 and 24 weeks
Change in Alanine Aminotransferase (ALT)
Time Frame: Baseline, 12 and 24 weeks
Change in ALT
Baseline, 12 and 24 weeks
Aspartate Aminotransferase (AST)
Time Frame: Baseline, 12 and 24 weeks
Change in AST
Baseline, 12 and 24 weeks
Gamma glutamyl transferase (GGT)
Time Frame: Baseline, 12 and 24 weeks
Change in GGT
Baseline, 12 and 24 weeks
Systolic blood pressure
Time Frame: Baseline, 12 and 24 weeks
Change in systolic blood pressure mg/dL
Baseline, 12 and 24 weeks
Diastolic blood pressure
Time Frame: Baseline, 12 and 24 weeks
Change in diastolic blood pressure (mg/dL)
Baseline, 12 and 24 weeks
Hemoglobin A1c
Time Frame: Baseline, 12 and 24 weeks
Change in hemoglobin A1c
Baseline, 12 and 24 weeks
HOMA-IR
Time Frame: Baseline, 12 and 24 weeks
Change in homeostatic model assessment of insulin resistance (HOMA-IR)
Baseline, 12 and 24 weeks
Adverse events
Time Frame: Baseline, 12 and 24 weeks
Number of adverse events compared between arms of the study
Baseline, 12 and 24 weeks
Percent responders
Time Frame: Baseline to 24 weeks
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Michigan State University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)
Emory University
Corewell Health West

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Miriam B Vos, MD, MSPH, Michigan State University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 26, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 26, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 17, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 5, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 9, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 1, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 28, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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