UNMASK: UNveiling the Pathobiology of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) for the Discovery of Novel Therapeutics and biomarKers (UNMASK)

June 11, 2026 updated by: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

UNMASK Study Protocol V2.0

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The UNMASK trial is a multicenter (Spain, Italy and Turkey), prospective, open-label lifestyle intervention based on tailored caloric restriction and monitored exercise. UNMASK aims to prove that the amelioration of MASLD at systemic and hepatic levels will be parallel to the improvement in our selected biomarkers. Given the known challenges with diagnosis and staging of MASH when using histopathological assessments of liver biopsies, the study will evaluate various blood-based non-invasive biomarkers. Non-invasive tests will be performed to asses endpoints. UNMASK includes a single arm in which patients undergo lifestyle changes, chiefly through the prescription of Mediterranean diet and physical exercise.

Study Type

Interventional

Enrollment (Estimated)

450

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Roma, Italy
        • Not yet recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Internal Medicine and Liver Transplantation Unit
        • Contact:
  • Spain
      • Seville, Spain
        • Recruiting
        • Hospital Universitario Virgen del Rocío de Sevilla
        • Principal Investigator:
          • Manuel Romero-Gómez
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Luis Calzadilla-Bertot
        • Sub-Investigator:
          • Rocío Gallego-Durán
  • Turkey (Türkiye)
      • Ankara, Turkey (Türkiye)
        • Not yet recruiting
        • Hacettepe University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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%. ,

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Multimodal lifestyle intervention
Mediterranean diet (MD) rich in olive oil, nuts and coffee, combined with structured exercise through a lifestyle intervention (LSI)
Behavioral: Multimodal lifestyle intervention
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Steatosis response
Time Frame: From baseline to month 16
Defined as a 30% decrease in MRI-Proton Density Fat Fraction (PDFF) and CAP assessed by Transient Elastography
From baseline to month 16
Fibrosis regression
Time Frame: From baseline to month 16
>20% reduction in liver stiffness measured by MRE.
From baseline to month 16
MASH resolution
Time Frame: From baseline to month 16
According to the non-invasive composite tool MASH Resolution Index (MASH-RI) (Stine et al Hep Comm 2025)
From baseline to month 16

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
% Change in Weight
Time Frame: From baseline to month 16
Weight measured in kilograms
From baseline to month 16
% Change in Waist Circumference
Time Frame: From baseline to month 16
Waist Circumference measured in centimeters
From baseline to month 16
Change in Patient Reported Physical Activity
Time Frame: From baseline to month 16
Assessment of patient reported physical activity using the International Physical Activity Questionnaire (IPAQ). IPAQ classifies individuals into five categories based on their total Metabolic Equivalent of Task (MET) minutes per week. Low physical activity: Less than 600 MET-minutes/week; moderate physical activity: Between 600 and 3,000 MET-minutes/week; or high physical activity: More than 3,000 MET-minute/week
From baseline to month 16
Change in Patient Reported Diet Habits by MEDAS Questionnaire
Time Frame: From baseline to month 16
Assessment of patient reported diet habits using the MEDAS questionnaire, a 14-item questionnaire of Mediterranean Diet adherence. Score lower than 9 means low adherence to Mediterranean Diet, and score equal or higher that 9 means good adherence to Mediterranean Diet.
From baseline to month 16

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Collaborators

Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Hacettepe University
Instituto de Salud Carlos III
Consorcio Centro de Investigación Biomédica en Red (CIBER)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 20, 2026

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

February 1, 2027

Study Registration Dates

First Submitted

June 11, 2026

First Submitted That Met QC Criteria

June 11, 2026

First Posted (Actual)

June 16, 2026

Study Record Updates

Last Update Posted (Actual)

June 16, 2026

Last Update Submitted That Met QC Criteria

June 11, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UNMASK-EPPERMED2024-496
  • EPPERMED2024-496 (Other Grant/Funding Number: ISCIII under the frame of EP PerMed)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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