MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)
Conditions
Keywords
Fibrosis, Obesity, Personalised Medicine, Patient Phenotyping, Lifestyle intervention
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.
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.
Interventions
BEHAVIORALMultimodal 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.
Sponsors
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Instituto de Salud Carlos III
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Hacettepe University
Consorcio Centro de Investigación Biomédica en Red (CIBER)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving a Steatosis Response | 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 | From baseline to month 16 | \>20% reduction in liver stiffness measured by MRE. |
| Change From Baseline in Metabolic Dysfunction-Associated Steatohepatitis Resolution Index Score | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| % Change in Weight | From baseline to month 16 | Weight measured in kilograms |
| % Change in Waist Circumference | From baseline to month 16 | Waist Circumference measured in centimeters |
| Change in Patient Reported Physical Activity | 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 |
| Change in Patient Reported Diet Habits by MEDAS Questionnaire | 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. |
Countries
Italy, Spain, Turkey (Türkiye)
Outcome results
None listed