Nutrition Intervention Combined With Resmetirom for MASH

Official title

Assessing Nutrition-aligned Resmetirom Roll-out

Overview

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.

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).

Interventions

• 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: 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 indep
• 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.

Primary outcome measures

• MRI-PDFF change [Time frame: Baseline and 12 months]
• MRE change [Time frame: Baseline and 12 months]

Secondary outcome measures (7)

• Controlled attenuation parameter (CAP) change [Time frame: Baseline, 6 months and 12 months]
• Vibration-controlled transient elastography (VCTE) responder [Time frame: Baseline, 6 months and 12 months]
• Plasma LDL-C responder [Time frame: Baseline, 6 months and 12 months]
• Triglyceride responder [Time frame: Baseline, 6 and 12 months]
• Apolipoprotein B change [Time frame: Baseline, 6 and 12 months]
• Lp(α) change [Time frame: Baseline, 6 and 12 months]
• ALT responder [Time frame: Baseline, 6 and 12 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• CUNY Graduate School of Public Health and Health Policy — New York

Identifiers

NCT: NCT07680478 · GR-00013739

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗