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

Overview

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.

Primary outcome measures

• Prevalence of liver steatosis and MASLD estimated by FibroScan CAP in patients at risk [Time frame: Baseline]
• Prevalence of liver fibrosis estimated by FibroScan LSM in patients at risk [Time frame: Baseline]
• Prevalence of at-risk MASH estimated by FAST score in patients at risk [Time frame: Baseline]
• *Subset of patients: prevalence of MASH in patients at risk [Time frame: 16 or 30 weeks]
• Comparison of the prevalence of MASLD, liver fibrosis and (at-risk) MASH between the participating countries [Time frame: Baseline (1-3) to 16/30 weeks for biopsy-confirmed MASH (4)]
• Evaluate added value of a 2-step pathway as compared to FibroScan only for detection of high-risk patients [Time frame: Baseline]

Secondary outcome measures (8)

• Build diagnostic model to identify MASH patients in a high-risk population [Time frame: Baseline]
• Genotypes related to MASH in different European countries: Exploratory [Time frame: Baseline]
• (Non-invasive) metabolite biomarkers identifying MASH in patients at risk: Exploratory [Time frame: Baseline]
• Prevalence of co-morbidities and associated therapies (especially for CVD) in patients with MASH compared to those without, in high-risk patient populations [Time frame: Baseline]
• Identify prognostic factors/biomarkers for complications in patients with MASLD and MASH by 5 years follow up [Time frame: Throughout follow-up (at 3 and 5 years)]
• Patient Reported Outcomes: Dietary habits and lifestyle [Time frame: Baseline + throughout follow-up (at 3 and 5 years)]
• *Subset of patients: Second FibroScan examination [Time frame: 14 weeks]
• Longitudinal changes in liver assessments [Time frame: Baseline, 14 weeks + throughout follow-up (at 3 and 5 years)]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Belgium · 2 centers

• Hôpital Erasme, Cliniques Universitaires De Bruxelles — Brussels
• Antwerp University Hospital — Antwerp

Germany · 2 centers

• Universitätsmedizin Mainz — Mainz
• Universitätsklinikum des Saarlandes — Homburg

Netherlands · 2 centers

• Amsterdam UMC — Amsterdam
• Franciscus Gasthuis & Vlietland — Rotterdam

Czechia · 1 center

• 4th internal clinic General University Hospital — Prague

France · 1 center

• Hôpital de la Pitié Salpêtrière — Paris

Greece · 1 center

• Harokopio University of Athens — Athens

Italy · 1 center

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS (FPG), Università Cattolica de — Rome

Portugal · 1 center

• ULSSM - Unidade Local de Saúde Santa Maria, E.P.E — Lisbon

Romania · 1 center

• Sacele Municipal Hospital — Săcele

Spain · 1 center

• Hospital Universitario Virgen del Rocío — Seville

Publications

• de Jong VD, Alings M, Bruha R, Cortez-Pinto H, Dedoussis GV, Doukas M, Francque S, Fournier-Poizat C, Gastaldelli A, Hankemeier T, Holleboom AG, Miele L, Moreno C, Muris JWM, Ratziu V, Romero-Gomez M, Schattenberg JM, Serfaty L, Stefan DC, Tushuizen ME, Verheij J, Willemse J, Franco OH, Grobbee DE, Castro Cabezas M; GRIPonMASH consortium. Global research initiative for patient screening on MASH (G PMID 40447415

Identifiers

NCT: NCT05651724 · GOM

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗