UNMASK: Unveiling the Pathobiology of Metabolic Dysfunction-Associated Steatotic Liver Disease for the Discovery of Novel Therapeutics and Biomarkers

NCT07652151 | Recruiting

• 2 other identifiers: UNMASK-EPPERMED2024-496EPPERMED2024-496
• Study Type: interventional
• Target: 450
• Locations: 3 countries
• Sites: 3

Brief Summary

Overall design: The study will include one intervention based on Mediterranean diet plus structured lifestyle intervention (150 min/week of moderate-intensity or 75 min/week of high-intensity exercise) for a total of 16 weeks. Following a screening period of up to 12 months, eligible participants will be included in a single cohort. Study details include:

• Study duration will be up to 36 months including the screening period.
• Intervention will be up to 16 weeks.
• Visit frequency will be every 4 weeks for the interventional period and every 12 weeks during follow-up.

Conditions

MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)

Keywords

Fibrosis; Obesity; Personalised Medicine; Patient Phenotyping; Lifestyle intervention

Outcome Measures

Primary Outcomes (3)

• Number of Participants Achieving a Steatosis Response

  Defined as a 30% decrease in MRI-Proton Density Fat Fraction (PDFF) and CAP assessed by Transient Elastography

  From baseline to month 16

• Number of Participants Achieving Fibrosis Regression

  \>20% reduction in liver stiffness measured by MRE.

  From baseline to month 16

• Change From Baseline in Metabolic Dysfunction-Associated Steatohepatitis Resolution Index Score

  Change from baseline to Month 16 in the Metabolic Dysfunction-Associated Steatohepatitis Resolution Index (MASH Resolution Index; MASH-RI), a composite non-invasive score developed to estimate resolution of steatohepatitis. The MASH-RI is calculated as: 0.520-0.003×baseline ALT (U/L)-0.024×(latest ALT (U/L)-baseline ALT (U/L))-0.048×baseline MRI-PDFF-2.571×(\[latest MRI-PDFF-baseline MRI-PDFF\]/baseline MRI-PDFF)-0.039×baseline AST (U/L). A MASH-RI ≥-0.67 rules in MASH resolution, and a MASH-RI of ≤-2.67 rules out a resolution.

  From baseline to month 16

Secondary Outcomes (4)

• % Change in Weight

  From baseline to month 16

• % Change in Waist Circumference

  From baseline to month 16

• Change in Patient Reported Physical Activity

  From baseline to month 16

• Change in Patient Reported Diet Habits by MEDAS Questionnaire

  From baseline to month 16

Study Arms (1)

Multimodal lifestyle intervention

EXPERIMENTAL

Mediterranean diet (MD) rich in olive oil, nuts and coffee, combined with structured exercise through a lifestyle intervention (LSI)

Behavioral: Multimodal lifestyle intervention

Interventions

Multimodal lifestyle intervention BEHAVIORAL

Mediterranean diet plus structured lifestyle intervention (150 min/week of moderate-intensity or 75 min/week of high-intensity exercise) for a total of 16 weeks.

Multimodal lifestyle intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metabolic disarrangements following ATPIII criteria (i.e. comorbidities such as Type 2 diabetes, central obesity, BMI≥\>25 kg/m2, hypertension, dyslipidaemia.
• Written informed consent
• No dietetical counsellor/weight loss higher than 10% within the prior 6 months
• Age over 18 years old
• Liver stiffness measurement by Fibroscan ≥ 8, CAP ≥ 248 db/m and MRI PDFF ≥ 5%. ,

You may not qualify if:

• Significant alcohol intake (≥30 g/day in men and ≥20 g/day in women)
• Other causes of liver disease (evidence of viral or autoimmune hepatitis, HIV, drug-induced fatty liver or other metabolic liver diseases)
• Use of recreational drugs
• Decompensated acute or chronic liver disease
• Cirrhosis or transplant waitlist
• Pregnancy or parenteral nutrition
• No nutritional interventions, medications for weight loss or weight loss higher than 5% within the last year
• Presence of other comorbidities that would impact lifestyle intervention (i. e. prosthesis)
• Absence of a personal smartphone with a compatible operating system capable of supporting the Amazfit Bip 6 accelerometer app's functionalities: Android 7.0 or iOS 14.0, or later.

Sponsors & Collaborators

• Fundación Pública Andaluza para la gestión de la Investigación en Sevilla: lead
• Instituto de Salud Carlos III: collaborator
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: collaborator
• Hacettepe University: collaborator
• Consorcio Centro de Investigación Biomédica en Red (CIBER): collaborator

Study Sites (3)

Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Internal Medicine and Liver Transplantation Unit

Roma, Italy

NOT YET RECRUITING

Hospital Universitario Virgen del Rocío de Sevilla

Seville, Spain

RECRUITING

Hacettepe University

Ankara, Turkey (Türkiye)

NOT YET RECRUITING

Related Links

• Description of the UNMASK Study within the EP PerMed project database, which currently lists transnational research and innovation projects in personalised medicine funded by EP PerMed

MeSH Terms

Conditions

Fibrosis; Obesity

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2026
• First Posted: June 16, 2026
• Study Start: January 20, 2026
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: June 23, 2026

Record last verified: 2026-05

Locations

IT (1); ES (1); TU (1)