A Phase 4 interventional study of Resmetirom therapy and Comprehensive nutritional intervention in Metabolic Dysfunction-Associated Steatohepatitis (MASH), sponsored by City University of New York. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-07-06.
Sponsored by City University of New York · Phase 4, Interventional, and Treatment
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.
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).
Exclusion Criteria:
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 · Behavioral: Comprehensive nutritional intervention
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 · Behavioral: Standard dietary support
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
The nutritional intervention will consist of two components: 1. 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. 2. 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.
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.
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
Time frame: 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
Time frame: Baseline and 12 months
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
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: Baseline, 6 and 12 months
Apolipoprotein B change
Change (%) from baseline in directly measured apolipoprotein B at months 6 and 12
Time frame: 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
Time frame: 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
Time frame: Baseline, 6 and 12 months
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)
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 3 months, 6 months, 9 months and 12 months
Dietary intake
Will be measured using a Food Frequency Questionnaire (FFQ)
Time frame: Baseline, 6 months and 12 months
Physical activity
Will be evaluated using the International Physical Activity Questionnaire
Time frame: Baseline, 6 and 12 months
Sleeping habits
Will be assessed using the single-item sleep quality scale questionnaire
Time frame: 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.
Time frame: Baseline, 6 months and 12 months
Alcohol consumption
will be evaluated using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire
Time frame: Baseline, 6 months and 12 months
Alcohol consumption blood biomarker
Will be assessed using the Phosphatidylethanol (PEth) test
Time frame: Baseline, 6 months and 12 months
Binge eating disorder
Will be assessed using the validated Being Eating Disorder Screener-7 (BEDS-7) questionnaire
Time frame: 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).
Time frame: 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)
Time frame: 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).
Time frame: 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
Time frame: 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 (%)
Time frame: 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.
Time frame: 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; %)
Time frame: 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.
Time frame: 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.
Time frame: Baseline, 6 and 12 months
Plan to share: Undecided
No publications or documents are linked to this record.
This study is not yet recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
City University of New York