Global Research Initiative for Patients Screening on MASH

Официальное название

Global Research Initiative for Patients Screening on MASH - Implementation of an International Transmural Patient Care Pathway

Обзор

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.

Подробное описание

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.

Первичные конечные точки

• Prevalence of liver steatosis and MASLD estimated by FibroScan CAP in patients at risk [Срок оценки: Baseline]
• Prevalence of liver fibrosis estimated by FibroScan LSM in patients at risk [Срок оценки: Baseline]
• Prevalence of at-risk MASH estimated by FAST score in patients at risk [Срок оценки: Baseline]
• *Subset of patients: prevalence of MASH in patients at risk [Срок оценки: 16 or 30 weeks]
• Comparison of the prevalence of MASLD, liver fibrosis and (at-risk) MASH between the participating countries [Срок оценки: 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 [Срок оценки: Baseline]

Вторичные конечные точки (8)

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

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Бельгия · 2 центра

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

Германия · 2 центра

• Universitätsmedizin Mainz — Mainz
• Universitätsklinikum des Saarlandes — Homburg

Нидерланды · 2 центра

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

Чехия · 1 центр

• 4th internal clinic General University Hospital — Prague

Франция · 1 центр

• Hôpital de la Pitié Salpêtrière — Paris

Греция · 1 центр

• Harokopio University of Athens — Athens

Италия · 1 центр

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

Португалия · 1 центр

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

Румыния · 1 центр

• Sacele Municipal Hospital — Săcele

Испания · 1 центр

• Hospital Universitario Virgen del Rocío — Seville

Публикации

• 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

Идентификаторы

NCT: NCT05651724 · GOM

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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