Global Research Initiative for Patients Screening on MASH - Implementation of an International Transmural Patient Care Pathway
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 10,000
- 试验地点
- 13
- 主要终点
- *Subset of patients: prevalence of MASH in patients at risk
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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)
排除标准
- •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.
结局指标
主要结局
*Subset of patients: prevalence of MASH in patients at risk
时间窗: 16 or 30 weeks
MASH diagnosis confirmed by histology (NAS/SAF criteria) upon liver biopsy; only in patients with \>12 kPa at 1st FibroScan or \>=8 kPa at 2nd FibroScan
Prevalence of liver steatosis and MASLD estimated by FibroScan CAP in patients at risk
时间窗: Baseline
Steatosis grade deduced from controlled attenuation parameter (CAP) measurement with Fibroscan
Evaluate added value of a 2-step pathway as compared to FibroScan only for detection of high-risk patients
时间窗: Baseline
Number of patients at risk identified by FIB-4 compared to numbers found using LSM by VCTE with FibroScan measurements, and numbers found in combination
Prevalence of liver fibrosis estimated by FibroScan LSM in patients at risk
时间窗: Baseline
Fibrosis stage deduced from liver stiffness measurement (LSM) by vibration controlled transient elastography (VCTE) measurement with Fibroscan
Comparison of the prevalence of MASLD, liver fibrosis and (at-risk) MASH between the participating countries
时间窗: Baseline (1-3) to 16/30 weeks for biopsy-confirmed MASH (4)
Prevalence (see outcome 1-4) stratified per country
Prevalence of at-risk MASH estimated by FAST score in patients at risk
时间窗: Baseline
At-risk MASH deduced from FAST score
次要结局
- (Non-invasive) metabolite biomarkers identifying MASH in patients at risk: Exploratory(Baseline)
- Identify prognostic factors/biomarkers for complications in patients with MASLD and MASH by 5 years follow up(Throughout follow-up (at 3 and 5 years))
- Patient Reported Outcomes: Dietary habits and lifestyle(Baseline + throughout follow-up (at 3 and 5 years))
- Longitudinal changes in liver assessments(Baseline, 14 weeks + throughout follow-up (at 3 and 5 years))
- Build diagnostic model to identify MASH patients in a high-risk population(Baseline)
- Prevalence of co-morbidities and associated therapies (especially for CVD) in patients with MASH compared to those without, in high-risk patient populations(Baseline)
- Genotypes related to MASH in different European countries: Exploratory(Baseline)
- *Subset of patients: Second FibroScan examination(14 weeks)