GRIP on NASH: Global Research Initiative for Patients Screening on NASH

Sponsor

Julius Clinical (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05651724

Collaborator

Sint Franciscus Gasthuis (Other), UMC Utrecht (Other), Erasmus Medical Center (Other)

10,000

Enrollment

98.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

GRIP on NASH will assist primary care physicians and 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 fatty liver disease and to raise awareness on fatty liver disease. The primary objective is to implement a transmural patient care pathway, in order to identify patients with non-alcoholic fatty liver diseases (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH) in primary care centres and clinics in 10 European countries.

Condition or Disease	Intervention/Treatment	Phase
NASH NAFLD NASH With Fibrosis Fibrosis, Liver Steatosis of Liver Type 2 Diabetes Obesity Metabolic Syndrome Arterial Hypertension

Detailed Description

GRIP on NASH 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 non-alcoholic fatty liver disease and liver fibrosis using two non-invasive tests (FIB-4 and FibroScan). Blood samples and liver biopsy material will be collected. Genomic, proteomic, metabolomic and lipidomic studies will be applied to gain a better understanding of the pathophysiology of non-alcoholic fatty liver disease 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.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

10000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Mar 31, 2031

Anticipated Study Completion Date :

Mar 31, 2031

Outcome Measures

Primary Outcome Measures

Prevalence of liver steatosis estimated by FibroScan in patients at risk coming from primary care [Baseline]
Steatosis grade deduced from controlled attenuation parameter (CAP) measurement with Fibroscan
Prevalence of liver fibrosis estimated by FibroScan in patients at risk coming from primary care [Baseline]
Fibrosis stage deduced from vibration controlled transient elastography (TE) measurement with Fibroscan
*Subset of patients: prevalence of NASH in patients at risk coming from primary care [15 weeks]
NASH diagnosis confirmed by histology (NAS criteria) upon liver biopsy; only in patients with persistent F2-F3 on FibroScan re-test at visit 3
Comparison of the prevalence of liver steatosis, liver fibrosis and NASH between the participating countries [Baseline (1,2) to 15 weeks for biopsy-confirmed NASH (3)]
Prevalence (see outcome 1, 2 and 3) stratified per country
Predictive power of non-invasive tests for detection of high-risk patients [Baseline]
FIB-4 scores in comparison to FibroScan measurements and FAST score, to identify patients at risk of liver steatosis and fibrosis

Secondary Outcome Measures

Build clinical prediction model to identify NASH patients in a high-risk population [Baseline]
Possible model parameters are all baseline clinical characteristics reported in the eCRF
Prevalence of relevant genotypes related to NASH in different European countries [Baseline]
Genomic and proteomic analysis on collected blood samples, including pre-identified genes of interest: PNPLA3, TM6SF2, HSD17B13, MBOAT7, GCKR
Non-invasive metabolite biomarkers identifying NASH in patients at risk: Exploratory [Baseline]
Mass-spectrometry (MS) based metabolomic and lipidomic analyses on collected blood and samples, both targeted and untargeted approaches.
Prevalence of co-morbidities and associated therapies (especially for CVD) in patients with NASH compared to those without, in high-risk patient populations [Baseline]
Prevalence of comorbidities, medication use, medical history
Identify prognostic factors for complications in patients with NAFLD and NASH by 5 years follow up [Throughout follow-up (at 3 and 5 years)]
Disease progression and liver-related and non-liver related complications
*Subset of patients: evaluate if a 12-week (unstandardized) lifestyle intervention, following routine practice, lowers liver fibrosis (from F2/F3 to F0/F1) [Week 14]
Revisited FibroScan measurements (CAP and TE) after 12 weeks of lifestyle intervention (intervention starts in week 2); intervention only offered to patients classified as F2/F3 in first FibroScan
Patient Reported Outcomes: Dietary habits [Baseline + throughout follow-up (at 3 and 5 years)]
14 item Mediterranean Diet Score; maximum score is 14, score >10 reflects adherence to Mediterranean diet
Patient Reported Outcomes: Disease-specific health-related Quality of Life (HR-QoL) [Baseline + throughout follow-up (at 3 and 5 years)]
Chronic Liver Disease Questionnaire - NAFLD NASH (CLDQ NAFLD-NASH); scores will be averaged for the 6 domains, higher scores reflect better HR-QoL

Other Outcome Measures

Estimation of the additional costs of implementing a patient care pathway as proposed in this study in clinical practice: Pilot [Baseline + throughout follow-up (at 3 and 5 years)]
Estimation of the actual costs of implementing the patient care pathway
Assess if implementation of the patient care pathway as proposed in this study increases awareness and knowledge of NAFLD and NASH management among participating physicians and clinicians [Baseline + throughout follow-up (at 3 and 5 years)]
Questionnaire send out to participating physicians and clinicians to assess awareness and knowledge of NAFLD and NASH management (questionairre to be developed within this study)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Obesity

Body mass index (BMI) > 30
Or waist circumferences (Europids): male ≥ 94 cm, female ≥ 80 cm

Arterial hypertension - Systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg

Metabolic syndrome

Central obesity defined as waist circumference (Europids): male ≥ 94 cm and female ≥ 80 cm (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, etc);
The patient is known with any other condition that may lead to liver fibrosis or cirrhosis;
(Excessive) alcohol use: > 3 units/day in males and > 2 units/day in females;
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.