Clinical trial NCT05651724: Global Research Initiative for Patients Screening on MASH
Official title: Global Research Initiative for Patients Screening on MASH - Implementation of an International Transmural Patient Care Pathway
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: MASH
MASLD
MASH With Fibrosis
Fibrosis, Liver
Steatosis of Liver
Type 2 Diabetes
Obesity
Metabolic Syndrome
Arterial Hypertension
Keywords: MASLD
MASH
Screening
Patient care pathway
Lead sponsor: Julius Clinical
Sponsor class: INDUSTRY
Collaborators: name: UMC Utrecht
name: Echosens
name: MIMETAS BV
name: Nordic Bioscience A/S
name: Elevate BV
name: Leiden University
name: Amsterdam University Medical Center
name: Andaluz Health Service
name: National Research Council, Institute of Clinical Physiology, Italy
name: Leiden University Medical Center
name: Université Libre de Bruxelles
name: University Hospital, Antwerp
name: Catholic University of the Sacred Heart
name: Medical Education Research And Innovation Center S.R.L.
name: EUROPEAN LIVER PATIENTS ASSOCIATION
name: Harokopio University
name: General University Hospital, Prague
name: Novo Nordisk A/S
name: Maastricht University
name: Mercodia Aktiebolag
name: EXIT071 BV
name: European Atherosclerosis Society
name: MetaDeq Limited
name: Associação para Investigação e Desenvolvimento da Faculdade de Medicina
name: Institute of Cardiometabolism and Nutrition, France
name: University Hospital, Saarland
name: Roche Pharma AG
name: Inventiva Pharma
name: Biocellvia
name: Franciscus Gasthuis & Vlietland (Hospital)
First posted: 2022-12-15
Enrollment: 10000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male and female patients aged 18-75 years with a current or prior diagnosis of at least one of the following four conditions: type 2 diabetes mellitus or metabolic syndrome or obesity or arterial hypertension. Subjects who meet the inclusion and exclusion criteria will be enrolled at primary care centers in one of the 10 countries.

Brief summary: GRIPonMASH will assist (primary) health care providers clinicians to implement the latest patient care pathway, as described by the European Association for the Study of the Liver (EASL), to identify patients at risk of severe metabolic dysfunction-associated steatotic liver disease (MASLD) and to raise awareness. The primary objective is to implement a transmural patient care pathway, in order to identify patients with MASLD and its progressive form metabolic dysfunction-associated steatohepatitis (MASH) in primary care centres and clinics in 10 European countries.

Detailed description: GRIPonMASH is an observational study in which 10.000 high risk patients (type 2 diabetes mellitus, metabolic syndrome, obesity or arterial hypertension) in 10 different European countries will be screened for the presence of MASLD, liver fibrosis and (at-rsik) MASH using at least two non-invasive tests (FIB-4 and FibroScan). Additional published and exploratory non-invasive test will also be investigated. Blood samples and liver biopsy material will be collected. Genomic, proteomic, metabolomic, lipidomic and fluxomic studies will be applied to gain a better understanding of the pathophysiology of MASLD and to identify (bio)markers that will help to detect patients at-risk. The predictive value of FIB-4 in relation to FibroScan results and liver biopsy will be analysed. Long-term follow-up of 5 years in all participants will provide insight into the natural history of the disease.

Eligibility criteria: Inclusion Criteria:

* Newly diagnosed subjects should fulfil criteria for diagnosis of type 2 diabetes mellitus or metabolic syndrome or obesity or arterial hypertension, following the study definitions.
* Subjects that are currently being treated for type 2 diabetes mellitus or metabolic syndrome or obesity or arterial hypertension, should have had a prior diagnosis based on study definitions.

Study definitions:

Type 2 diabetes mellitus

* At least 2 times a fasting glucose \> 7,0 mmol/L
* Or elevated non-fasting glucose \>11,1 mmol/L 2 hrs after OGTT
* Or HbA1c ≥48 mmol/mol (≥6.5%)
* Or being actively treated for previously diagnosed type 2 diabetes by a health care provider

Obesity

* Body mass index (BMI) \> 30
* Or waist circumferences Caucasian: male ≥ 94 cm, female ≥ 80 cm South-Asian/Chinese: male ≥90 cm, female ≥80 cm Japanese: male ≥85 cm, female ≥90 cm

Arterial hypertension

* Systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg
* Or being actively treated for previously diagnosed arterial hypertension by a health care provider

Metabolic syndrome

- Central obesity defined as waist circumference (see above), if BMI is \>30 kg/m2, central obesity can be assumed and waist circumference does not need to be measured

AND any two of the following:

* Raised triglycerides: ≥ 150 mg/dL (1.7 mmol/L), or specific treatment for this lipid abnormality
* Reduced HDL cholesterol: \< 40 mg/dL (1.03 mmol/L) in males, \< 50 mg/dL (1.29 mmol/L) in females, or specific treatment for this lipid abnormality
* Raised blood pressure (BP): systolic BP ≥ 130 or diastolic BP ≥ 85 mm Hg, or treatment of previously diagnosed hypertension
* Raised fasting plasma glucose (FPG): FGP ≥ 100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetes (if above \>5.6 mmol/L or 100 mg/dL, an oral glucose tolerance test is strongly recommended, but is not necessary to define presence of the syndrome)

Exclusion Criteria:

* The patient is known with hepatitis B, C or HIV or any other liver condition (like hemochromatosis, sarcoidosis, Wilson's disease etc);
* The patient is known with any other condition that may lead to liver fibrosis or cirrhosis;
* The patient engages in (excessive) alcohol use: \> 3 units/day in males \[30 grams/day\] and \> 2 units/day in females \[20 grams/day\];
* The patient has a history or evidence of any other clinically significant condition or planned or expected procedure that in the opinion of the Investigator, may compromise the patient's safety or ability to be included in this study;
* The patient is an employee or contractor of the facility that is conducting the study or is a family member of the Investigator, sub-Investigator, or any Sponsor personnel;
* The patient is not able to understand the details of the protocol and/or is not able to provide written informed consent;
* The patient is pregnant or breastfeeding.
* The patient underwent bariatric surgery in the last 12 months.

Primary outcomes:
measure: Prevalence of liver steatosis and MASLD estimated by FibroScan CAP in patients at risk
timeFrame: Baseline
measure: Prevalence of liver fibrosis estimated by FibroScan LSM in patients at risk
timeFrame: Baseline
measure: Prevalence of at-risk MASH estimated by FAST score in patients at risk
timeFrame: Baseline
measure: *Subset of patients: prevalence of MASH in patients at risk
timeFrame: 16 or 30 weeks
measure: Comparison of the prevalence of MASLD, liver fibrosis and (at-risk) MASH between the participating countries
timeFrame: Baseline (1-3) to 16/30 weeks for biopsy-confirmed MASH (4)
measure: Evaluate added value of a 2-step pathway as compared to FibroScan only for detection of high-risk patients
timeFrame: Baseline
Secondary outcomes:
measure: Build diagnostic model to identify MASH patients in a high-risk population
timeFrame: Baseline
measure: Genotypes related to MASH in different European countries: Exploratory
timeFrame: Baseline
measure: (Non-invasive) metabolite biomarkers identifying MASH in patients at risk: Exploratory
timeFrame: Baseline
measure: Prevalence of co-morbidities and associated therapies (especially for CVD) in patients with MASH compared to those without, in high-risk patient populations
timeFrame: Baseline
measure: Identify prognostic factors/biomarkers for complications in patients with MASLD and MASH by 5 years follow up
timeFrame: Throughout follow-up (at 3 and 5 years)
measure: Patient Reported Outcomes: Dietary habits and lifestyle
timeFrame: Baseline + throughout follow-up (at 3 and 5 years)
measure: *Subset of patients: Second FibroScan examination
timeFrame: 14 weeks
measure: Longitudinal changes in liver assessments
timeFrame: Baseline, 14 weeks + throughout follow-up (at 3 and 5 years)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Hôpital Erasme, Cliniques Universitaires De Bruxelles
state: Vlaams-brabant
city: Antwerp
country: Belgium
facility: Antwerp University Hospital
city: Prague
country: Czechia
facility: 4th internal clinic General University Hospital
state: Bohemia
city: Paris
country: France
facility: Hôpital de la Pitié Salpêtrière
state: Il-de-France
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
state: Rhineland-Palatinate
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes
state: Saarland
city: Athens
country: Greece
facility: Harokopio University of Athens
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS (FPG), Università Cattolica del Sacro Cuore (UCSC)
state: Lazio
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
state: Zuid-holland
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis & Vlietland
state: Zuid-Holland
city: Lisbon
country: Portugal
facility: ULSSM - Unidade Local de Saúde Santa Maria, E.P.E
city: Sacele
country: Romania
facility: Sacele Municipal Hospital
state: Brasov
city: Seville
country: Spain
facility: Hospital Universitario Virgen del Rocío
Study officials:
affiliation: Sint Franciscus Gasthuis
name: Manuel Castro Cabezas, MD/PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UMC Utrecht
name: Diederick E. Grobbee, MD/PhD/FESC
role: PRINCIPAL_INVESTIGATOR
affiliation: UMC Utrecht
name: Oscar H. Franco, MD/PhD/FESC/FFPH
role: STUDY_CHAIR
References: