Nutrition Intervention Combined With Resmetirom for MASH (NOURISH-MASH)

Assessing Nutrition-aligned Resmetirom Roll-out

This randomized control trial aims to evaluate the effectiveness of combining resmetirom therapy (first approved pharmacological therapy for treating metabolic dysfunction-associated steatohepatitis (MASH)) with a nutritional intervention compared to resmetirom therapy alone over one year in improving liver health among 120 patients living with non-cirrhotic MASH. We hypothesize that patients receiving resmetirom and nutritional intervention will experience more significant improvements in liver function than those receiving only resmetirom therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Metabolic Dysfunction-Associated Steatohepatitis (MASH)
• Intervention / Treatment: Drug: Resmetirom therapy; Behavioral: Comprehensive nutritional intervention; Behavioral: Standard dietary support

Detailed Description

On March 14, 2024, resmetirom, a selective thyroid hormone receptor-β agonist, became the first pharmacological therapy approved by the US Food and Drug Administration (FDA) for treating metabolic dysfunction-associated steatohepatitis (MASH). Although, lifestyle modification remains first-line MASH treatment the provision of resmetirom is rarely accompanied by structured non-pharmacological interventions, and evidence guiding the integration of nutrition-based strategies with pharmacotherapy is limited. This study aims to evaluate the effectiveness of a nutrition-based intervention, including medically tailored meal (MTM) and nutrition education provision combined with resmetirom therapy, compared with resmetirom therapy combined with standard-of-care lifestyle recommendations, in improving liver function.

This multi-site, prospective, randomised controlled trial will enroll 120 adults (18-75 years) with non-cirrhotic MASH and fibrosis stages F2-F3. Recruited participants will undergo baseline assessments including evaluation of medical history and lifestyle behaviors, completion of a food frequency questionnaire, blood pressure measurement, blood sampling, anthropometric measurements (weight, height, and waist and hip circumference), and assessment of liver steatosis and fibrosis using imaging methods. Upon completion of baseline evaluations, participants will be randomised 1:1 to receive either: (1) resmetirom plus standard-of-care lifestyle education (control); or (2) resmetirom plus a structured nutritional intervention consisting of MTM delivery and lifestyle education (intervention).

The primary endpoints are changes in liver steatosis and fibrosis at 12 months, assessed by imaging methods. Secondary endpoints include changes in blood-circulating lipids, alanine aminotransferase levels, metabolic parameters, anthropometrics, dietary quality, and lifestyle behaviours. Analyses will follow an intention-to-treat approach using regression models adjusted for relevant covariates.

Adherence assessments will be conducted at 3, 6, and 9 months, with outcome evaluations at 6 months and at the end of the study (12 months).

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jeffrey V. Lazarus; Phone Number: +1 646-364-9600; Email: Jeffrey.Lazarus@sph.cuny.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10027
      • CUNY Graduate School of Public Health and Health Policy
      • Contact: Saba Mohamed Bibi; Phone Number: 932 27 18 06; Email: saba.mohamed@isglobal.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provide informed consent
• Be 18-75 years old
• Have non-cirrhotic MASH with fibrosis stage F2-F3 (VCTE 8-20 kPa and CAP =280 dB/m)
• Be initiating resmetirom per standard of care
• Be able to comply with study procedures, including fasting visits
• Reside in one of the five New York City boroughs

Exclusion Criteria:

• Have cirrhosis or decompensated liver disease
• Have other chronic liver diseases
• Are pregnant or breastfeeding
• Consume alcohol above defined thresholds or have PEth =20 ng/mL
• Have recent major surgery or hospitalization
• Are on glucagon-like peptide-1 agonist therapy (e.g., exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, semaglutide and albiglutide), unless the dose is stable for 12 weeks prior to the baseline evaluation and they have not experienced a >5% weight loss in the 6 months preceding resmetirom initiation.
• Are undergoing bariatric surgery
• Are living with any other end-stage organ disease (e.g., heart, lung or kidney failure requiring dialysis) or have any active malignancy in the last 5 years.
• Have conditions preventing consumption of provided meals

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Resmetirom plus medically tailored meals and lifestyle education; Participants receive resmetirom once daily by weight-based dosing (80 mg if <100 kg; 100 mg if ≥100 kg) plus 10 medically tailored meals per week based on Mediterranean-diet principles, along with online nutrition and physical activity education at baseline and follow-up.	Drug: Resmetirom therapy; All participants involved in the study will receive treatment according to resemetirom protocol: For patients weighing: <100 kg, the recommended dosage is 80 mg orally, once daily; ≥100 kg, the recommended dosage is 100 mg orally, once daily; Behavioral: Comprehensive nutritional intervention; The nutritional intervention will consist of two components: Medically tailored meals (MTMs): Participants will receive 10 MTMs per week delivered by God's Love We Deliver in New York City. Meals will follow Mediterranean diet principles (40% carbohydrate, 35-45% fat, 15-25% protein), be delivered frozen with preparation and safety instructions, and meal preferences will be collected in advance. Participants will be encouraged to eat two meals per weekday and source any additional food independently.; Nutritional and physical activity educational support: Online educational materials will be provided at baseline and follow-up visits, covering healthy eating, Mediterranean-diet principles, and exercise recommendations.
Active Comparator: Resmetirom plus standard-of-care lifestyle education; Participants receive the same resmetirom protocol once daily by weight-based dosing (80 mg if <100 kg; 100 mg if ≥100 kg), plus healthy diet and physical activity handouts and the option of a telehealth consultation with a dietitian.	Drug: Resmetirom therapy; All participants involved in the study will receive treatment according to resemetirom protocol: For patients weighing: <100 kg, the recommended dosage is 80 mg orally, once daily; ≥100 kg, the recommended dosage is 100 mg orally, once daily; Behavioral: Standard dietary support; Participants will receive standard-of-care lifestyle recommendations, including handouts on healthy diet and physical activity, and the option of a telehealth consultation with a dietitian.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI-PDFF change	Magnetic resonance imaging derived proton-density-fat-fraction (MRI-PDFF) will be used to evaluate liver steatosis. Absolute change in MRI-PDFF (%) between the two groups at month 12, as an indicator for steatosis change	Baseline and 12 months
MRE change	Magnetic resonance elastography (MRE) will be used to evaluate liver fibrosis. Absolute change in MRE (kPa) between the two groups at month 12	Baseline and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Controlled attenuation parameter (CAP) change	The CAP will be used to assess liver steatotis. Absolute change in CAP (dB/m) between the two groups at month 12	Baseline, 6 months and 12 months
Vibration-controlled transient elastography (VCTE) responder	The VSTE will be used to assess liver fibrosis. The percentage of patients that achieve a ≥25% relative reduction at months 6 and 12, as compared with baseline VCTE (kPa)	Baseline, 6 months and 12 months
Plasma LDL-C responder	The percentage of patients with plasma LDL-C >100 mg/dL at baseline who are able to reduce it to <100 mg/dL at months 6 and 12	Baseline, 6 months and 12 months
Triglyceride responder	The percentage of patients with triglycerides >150 mg/dL at baseline who are able to reduce it to <150 mg/dL at months 6 and 12	Baseline, 6 and 12 months
Apolipoprotein B change	Change (%) from baseline in directly measured apolipoprotein B at months 6 and 12	Baseline, 6 and 12 months
Lp(α) change	Change (%) from baseline in directly measured Lp(α) in patients with baseline Lp(α) >10 nmol/L at months 6 and 12	Baseline, 6 and 12 months
ALT responder	The percentage of patients with ALT >30 IU/L at baseline with a >20% and/or 17 IU/L reduction at months 6 and 12	Baseline, 6 and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight reduction	The percentage of patients that achieve a ≥5% relative reduction in weight (Kg) at months 6 and 12, as compared with baseline weight (Kg)	Baseline, 6 months and 12 months
Waist to hip ratio	The waist-to-hip ratio will be calculated by dividing the waist circumference (cm) by the hip circumference (cm). Waist circumference will be measured at the narrowest part of the waist (or midway between the lowest rib and the top of the hip bone), and hip circumference will be measured at the widest part of the buttocks. A higher waist-to-hip ratio indicates a greater proportion of abdominal fat relative to hip circumference.	Baseline, 6 months and 12 months
BMI	Body mass index (BMI) will be calculated by dividing a person's weight in kilograms by the square of their height in meters (weight [kg] ÷ height [m²]). BMI is commonly used as a screening measure to classify body weight relative to height and to identify categories such as underweight, normal weight, overweight, and obesity.	Baseline, 6 and 12 months
Medication adherence	At each study visit, participants will bring any remaining resmetirom pills. Study staff will count the pills and compare this to the number dispensed. Adherence is defined as taking at least 80% of dispensed medication.	3 months, 6 months, 9 months and 12 months
Medication adherence blood biomarker	Serum sex hormone-binding globulin (SHBG) concentrations will be measured using a standardized immunoassay and reported in nanomoles per liter (nmol/L). SHBG is a glycoprotein produced primarily by the liver and is regulated, in part, by thyroid hormone receptor beta (THR-β) signaling. As SHBG is a downstream target of THR-β agonism, increases in SHBG levels have been observed following treatment with the THR-β agonist resmetirom and may serve as a pharmacodynamic marker of hepatic drug exposure. Therefore, SHBG levels will be assessed as an indirect measure of treatment adherence and biological response to resmetirom therapy.	3 months, 6 months, 9 months and 12 months
Dietary intake	Will be measured using a Food Frequency Questionnaire (FFQ)	Baseline, 6 months and 12 months
Physical activity	Will be evaluated using the International Physical Activity Questionnaire	Baseline, 6 and 12 months
Sleeping habits	Will be assessed using the single-item sleep quality scale questionnaire	Baseline, 6 months and 12 months
Smoking habits	Will be assessed by pack years calculation. Pack-years will be calculated by dividing the average number of cigarettes smoked per day by 20 (the number of cigarettes in a standard pack) and multiplying the result by the total number of years the person has smoked.	Baseline, 6 months and 12 months
Alcohol consumption	will be evaluated using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire	Baseline, 6 months and 12 months
Alcohol consumption blood biomarker	Will be assessed using the Phosphatidylethanol (PEth) test	Baseline, 6 months and 12 months
Binge eating disorder	Will be assessed using the validated Being Eating Disorder Screener-7 (BEDS-7) questionnaire	Baseline, 6 months and 12 months
Liver enzymes	Liver enzymes will be measured using automated enzymatic assays and will include alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Results will be reported in units per liter (U/L).	Baseline, 6 and 12 months
Fasting plasma glucose	Fasting plasma glucose will be measured using an enzymatic assay and reported in milligrams per deciliter (mg/dL)	Baseline, 6 and 12 months
Fasting insulin	Fasting insulin concentrations will be measured using a standardized immunoassay and reported in micro-international units per milliliter (μIU/mL).	Baseline, 6 and 12 months
Insulin resistance	Insulin resistance will be assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). HOMA-IR will be calculated from fasting plasma glucose and fasting insulin concentrations using the following formula: HOMA-IR = [fasting insulin (μIU/mL) × fasting glucose (mg/dL)] ÷ 405 Higher HOMA-IR values indicate greater insulin resistance. There is no universally accepted cutoff for insulin resistance, as values vary according to age, sex, ethnicity, and study population. In adults, HOMA-IR values above approximately 2.0-2.5 are often considered suggestive of insulin resistance, while values above 3.0 are generally considered indicative of significant insulin resistance. HOMA-IR will also be analyzed as a continuous variable or categorized according to population-specific upper quartile	Baseline, 6 and 12 months
Hemoglobin A1c	Hemoglobin A1c (HbA1c) will be measured using a standardized assay certified according to international guidelines and reported as a percentage (%)	Baseline, 6 and 12 months
Estimated glomerular filtration rate (eGFR)	Estimated glomerular filtration rate (eGFR) is a widely used measure of the kidneys' ability to filter blood. The eGFR will be calculated from serum creatinine concentrations using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which incorporates age and sex. Results will be reported in milliliters per minute per 1.73 square meters of body surface area (mL/min/1.73 m²). Higher eGFR values indicate better kidney function, whereas lower values indicate impaired kidney function. An eGFR of 90 mL/min/1.73 m² or higher is generally considered normal, provided there is no other evidence of kidney damage. Values between 60 and 89 mL/min/1.73 m² may reflect mildly reduced kidney function, while an eGFR below 60 mL/min/1.73 m² persisting for at least three months is commonly used as a criterion for chronic kidney disease (CKD). An eGFR below 30 mL/min/1.73 m² indicates severe kidney impairment.	Baseline, 6 and 12 months
Complete blood count	A complete blood count (CBC) will be performed using an automated hematology analyzer. Parameters will include: Hemoglobin (g/dL) White blood cell count (×10⁹/L) Platelet count (×10⁹/L) Red blood cell count (×10¹²/L) Hematocrit (%) Mean corpuscular volume (MCV; fL) Mean corpuscular hemoglobin (MCH; pg) Mean corpuscular hemoglobin concentration (MCHC; g/dL) Red cell distribution width (RDW; %)	Baseline, 6 and 12 months
Blood pressure measurements	Blood pressure will be measured using a validated automated sphygmomanometer according to standard clinical procedures. Participants will be seated comfortably with their back supported and feet flat on the floor for at least 5 minutes before the measurement. Blood pressure will be measured in the upper arm using an appropriately sized cuff. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) will be recorded in millimeters of mercury (mmHg). Blood pressure values will be analyzed as continuous variables, and participants may also be categorized according to established hypertension guidelines.	Baseline, 6 and 12 months
Serum free thyroxine (FT4) concentrations	Serum free thyroxine (FT4) concentrations will be measured using a standardized immunoassay. FT4 is the biologically active fraction of thyroxine and is commonly used to assess thyroid function and monitor the safety of therapies that may affect the thyroid gland. Results will be reported in nanograms per deciliter (ng/dL). Changes in FT4 concentrations from baseline to follow-up will be evaluated, and the percentage change will be analyzed as a continuous variable to assess the safety of the intervention.	Baseline, 6 and 12 months

Collaborators and Investigators

• Sponsor: City University of New York

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: June 18, 2026
• First Submitted That Met QC Criteria: June 25, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 25, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: MASLD/MASH; Resmetirom therapy; Medically tailored meal (MTM); Nutrition-based intervention
• Other Study ID Numbers: GR-00013739

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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