MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)UNMASKNCT07652151
UNMASK: Unveiling the Pathobiology of Metabolic Dysfunction-Associated Steatotic Liver Disease for the Discovery of Novel Therapeutics and Biomarkers
A study testing Multimodal lifestyle intervention in people with MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease), run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 3 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)
- What is being tested?
- Multimodal lifestyle intervention
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 450 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 20 Jan 2026to Feb 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%. ,
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
3 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 3 countries
Italy1 site, 1 recruiting
- Not yet recruiting
Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Internal Medicine and Liver Transplantation Unit
Roma
Luca Miele, 00390630154469, luca.miele@policlinicogemelli.it
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitario Virgen del Rocío de Sevilla
Seville
Manuel Romero-Gómez, +34954786587, mromerogomez@us.es
Luis Calzadilla-Bertot, luis.calzadilla@ciberehd.org
Turkey (Türkiye)1 site, 1 recruiting
- Not yet recruiting
Hacettepe University
Ankara
Yasemin Balaban, +90 533 234 4232, ybalaban@hacettepe.edu.tr
About this study
Official title: UNMASK: Unveiling the Pathobiology of Metabolic Dysfunction-Associated Steatotic Liver Disease for the Discovery of Novel Therapeutics and Biomarkers - Study Protocol Version 2.0
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.
Read the 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.
- Being tested
- Multimodal lifestyle intervention
- Keywords
- Fibrosis, Obesity, Personalised Medicine, Patient Phenotyping, Lifestyle intervention
- Medical subject headings
- Fibrosis, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multimodal lifestyle interventionBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Multimodal lifestyle intervention | Experimental | Mediterranean diet (MD) rich in olive oil, nuts and coffee, combined with structured exercise through a lifestyle intervention (LSI) Receives: Behavioral: Multimodal lifestyle intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: From baseline to month 16
Number of Participants Achieving Fibrosis Regression
>20% reduction in liver stiffness measured by MRE.
Measured: 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.
Measured: From baseline to month 16
Secondary outcomes (4)
% Change in Weight
Weight measured in kilograms
Measured: From baseline to month 16
% Change in Waist Circumference
Waist Circumference measured in centimeters
Measured: From baseline to month 16
Change in Patient Reported Physical Activity
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
Measured: From baseline to month 16
Change in Patient Reported Diet Habits by MEDAS Questionnaire
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.
Measured: From baseline to month 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2026
- Study start20 Jan 2026
- Primary completionNov 2026 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto de Salud Carlos III, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Hacettepe University, Consorcio Centro de Investigación Biomédica en Red (CIBER)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07652151
- Sponsor's protocol ID
- UNMASK-EPPERMED2024-496
- Other IDs
- EPPERMED2024-496
- Acronym
- UNMASK
- Status last verified
- May 2026
- First submitted
- 11 Jun 2026
- Last updated
- 23 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- UNMASK: Unveiling the Pathobiology of Metabolic Dysfunction-Associated Steatotic Liver Disease for the Discovery of Novel Therapeutics and Biomarkers - Study Protocol Version 2.0
- ClinicalTrials.gov ID
- NCT07652151
- Acronym / sponsor ID
- UNMASK / UNMASK-EPPERMED2024-496
- Keywords
- Fibrosis, Obesity, Personalised Medicine, Patient Phenotyping, Lifestyle intervention
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en SevillaUniversity, hospital or other
- Collaborators
- Instituto de Salud Carlos III, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Hacettepe University, Consorcio Centro de Investigación Biomédica en Red (CIBER)
- Study start
- 20 Jan 2026 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 16 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Multimodal lifestyle intervention | Experimental | Behavioral: Multimodal lifestyle interventionMediterranean diet (MD) rich in olive oil, nuts and coffee, combined with structured exercise through a lifestyle intervention (LSI) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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%. ,
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multimodal lifestyle interventionMediterranean 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. | Behavioural | Multimodal lifestyle intervention |
Primary outcome
Number of Participants Achieving a 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
Number of Participants Achieving Fibrosis Regression
Time frame: From baseline to month 16
>20% reduction in liver stiffness measured by MRE.
Change From Baseline in Metabolic Dysfunction-Associated Steatohepatitis Resolution Index Score
Time frame: From baseline to month 16
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.
4 secondary outcomes
% Change in Weight
Time frame: From baseline to month 16
% Change in Waist Circumference
Time frame: From baseline to month 16
Change in Patient Reported Physical Activity
Time frame: From baseline to month 16
Change in Patient Reported Diet Habits by MEDAS Questionnaire
Time frame: From baseline to month 16
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2026.
- 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 PerMedLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Internal Medicine and Liver Transplantation Unit
Roma, Italy
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Multimodal lifestyle intervention in people with MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease), run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy, Spain, Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Achieving a Steatosis Response (time frame: From baseline to month 16). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.