Global Research Initiative for Patients Screening on NASH

Obesity Clinical Trial

— GRIP on NASH  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05651724
• Other study ID #: GON1
• Status: Not yet recruiting
• Start date: January 1, 2023
• Est. completion date: March 31, 2031

Study information

• Verified date: December 2022
• Source: Julius Clinical
• Contact: Vivian D de Jong, MSc
• Phone: +31628259968
• Email: vivian.dejong[@]juliusclinical.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10000
• Est. completion date: March 31, 2031
• Est. primary completion date: March 31, 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arterial Hypertension
• Fatty Liver
• Fibrosis
• Fibrosis, Liver
• Hypertension
• Liver Cirrhosis
• Metabolic Syndrome
• NAFLD
• NASH
• Obesity
• Steatosis of Liver
• Type 2 Diabetes

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Julius Clinical	Erasmus Medical Center, Sint Franciscus Gasthuis, UMC Utrecht

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Estimation of the additional costs of implementing a patient care pathway as proposed in this study in clinical practice: Pilot	Estimation of the actual costs of implementing the patient care pathway	Baseline + throughout follow-up (at 3 and 5 years)
Other	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	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)	Baseline + throughout follow-up (at 3 and 5 years)
Primary	Prevalence of liver steatosis estimated by FibroScan in patients at risk coming from primary care	Steatosis grade deduced from controlled attenuation parameter (CAP) measurement with Fibroscan	Baseline
Primary	Prevalence of liver fibrosis estimated by FibroScan in patients at risk coming from primary care	Fibrosis stage deduced from vibration controlled transient elastography (TE) measurement with Fibroscan	Baseline
Primary	*Subset of patients: prevalence of NASH in patients at risk coming from primary care	NASH diagnosis confirmed by histology (NAS criteria) upon liver biopsy; only in patients with persistent F2-F3 on FibroScan re-test at visit 3	15 weeks
Primary	Comparison of the prevalence of liver steatosis, liver fibrosis and NASH between the participating countries	Prevalence (see outcome 1, 2 and 3) stratified per country	Baseline (1,2) to 15 weeks for biopsy-confirmed NASH (3)
Primary	Predictive power of non-invasive tests for detection of high-risk patients	FIB-4 scores in comparison to FibroScan measurements and FAST score, to identify patients at risk of liver steatosis and fibrosis	Baseline
Secondary	Build clinical prediction model to identify NASH patients in a high-risk population	Possible model parameters are all baseline clinical characteristics reported in the eCRF	Baseline
Secondary	Prevalence of relevant genotypes related to NASH in different European countries	Genomic and proteomic analysis on collected blood samples, including pre-identified genes of interest: PNPLA3, TM6SF2, HSD17B13, MBOAT7, GCKR	Baseline
Secondary	Non-invasive metabolite biomarkers identifying NASH in patients at risk: Exploratory	Mass-spectrometry (MS) based metabolomic and lipidomic analyses on collected blood and samples, both targeted and untargeted approaches.	Baseline
Secondary	Prevalence of co-morbidities and associated therapies (especially for CVD) in patients with NASH compared to those without, in high-risk patient populations	Prevalence of comorbidities, medication use, medical history	Baseline
Secondary	Identify prognostic factors for complications in patients with NAFLD and NASH by 5 years follow up	Disease progression and liver-related and non-liver related complications	Throughout follow-up (at 3 and 5 years)
Secondary	*Subset of patients: evaluate if a 12-week (unstandardized) lifestyle intervention, following routine practice, lowers liver fibrosis (from F2/F3 to F0/F1)	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	Week 14
Secondary	Patient Reported Outcomes: Dietary habits	14 item Mediterranean Diet Score; maximum score is 14, score >10 reflects adherence to Mediterranean diet	Baseline + throughout follow-up (at 3 and 5 years)
Secondary	Patient Reported Outcomes: Disease-specific health-related Quality of Life (HR-QoL)	Chronic Liver Disease Questionnaire - NAFLD NASH (CLDQ NAFLD-NASH); scores will be averaged for the 6 domains, higher scores reflect better HR-QoL	Baseline + throughout follow-up (at 3 and 5 years)