Metabolic Dysfunction-Associated Steatohepatitis (MASH)
Conditions
Keywords
MASLD/MASH, Resmetirom therapy, Medically tailored meal (MTM), Nutrition-based intervention
Brief summary
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
DRUGResmetirom 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
BEHAVIORALComprehensive 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 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.
BEHAVIORALStandard 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.
Sponsors
City University of New York
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MRI-PDFF change | Baseline and 12 months | 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 |
| MRE change | Baseline and 12 months | Magnetic resonance elastography (MRE) will be used to evaluate liver fibrosis. Absolute change in MRE (kPa) between the two groups at month 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Controlled attenuation parameter (CAP) change | Baseline, 6 months and 12 months | The CAP will be used to assess liver steatotis. Absolute change in CAP (dB/m) between the two groups at month 12 |
| Vibration-controlled transient elastography (VCTE) responder | Baseline, 6 months and 12 months | 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) |
| Plasma LDL-C responder | Baseline, 6 months and 12 months | 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 |
| Triglyceride responder | Baseline, 6 and 12 months | 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 |
| Apolipoprotein B change | Baseline, 6 and 12 months | Change (%) from baseline in directly measured apolipoprotein B at months 6 and 12 |
| Lp(α) change | Baseline, 6 and 12 months | Change (%) from baseline in directly measured Lp(α) in patients with baseline Lp(α) \>10 nmol/L at months 6 and 12 |
| ALT responder | Baseline, 6 and 12 months | 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 |
Countries
United States
Contacts
CONTACTJeffrey V. Lazarus
Outcome results
None listed