Clinical trial NCT06688149: NASH Patient's Itinerary: Comparison of Strategies for Screening, Referring and Management of Diabetic Patients
Official title: NASH Patient's Itinerary: Comparison of Strategies for Screening, Referring and Management of Diabetic Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-alcoholic Fatty Liver Disease (NAFLD)
Keywords: NAFLD
MASLD
NASH
MASH
FIBROSIS
NITs
TRANSIENT ELASTOGRAPHY
FIB4
NFS
HFS
DIABETES
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
name: Barcelona Institute for Global Health
name: Harokopio University
name: University Medical Center Mainz
name: University Düsseldorf
First posted: 2024-11-14
Enrollment: 536
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent, underdiagnosed, health system burden and impacts on quality of life including comorbidities in the affected population. Cost-effective strategies focusing on clinical pathways to detect and refer patients to care are needed. The aim of this study is to build a stepwise algorithm combining non-invasive freely available methods (FIB-4, NFS, HFS alone or combined) and vibration-controlled transient elastography (VCTE) in diabetic patients from primary care and endocrinology units.

Detailed description: NAFLD is a growing health concern and liver fibrosis severity determines its prognosis. The burden of this disease has been estimated in a quarter of the European population and is even higher in diabetic patients, where it raises significantly and can reach up to 80%. The fact that only 10% of these patients will develop significant fibrosis, the strongest predictor of liver-specific morbidity and overall mortality, leads to an overwhelming situation in primary care and endocrine units, where physicians need to screen large numbers of patients to identify individuals with a high risk for developing fibrosis that should be derived to a specialized hepatology unit. New free and accurate non- invasive tests need to be available to be used in primary care and non-hepatologists units to fight against this disappointing situation.

Several non-invasive methods, based on serum and imaging biomarkers, have aimed to identify at-risk patients for NAFLD-related fibrosis, but inconclusive results and many phenotypes that are present or not in patients (diabetes mellitus, obesity and age) reduce their diagnostic accuracy. Current strategies to monitor fibrosis are, therefore, inefficient and often fail to easily distinguish patients with mild disease that can be monitored at primary care from those at risk of advanced fibrosis or cirrhosis that need to receive specialised care and that could benefit from therapeutic interventions, such as participation in clinical trials and liver cancer surveillance programs.

The majority of patients with NAFLD are followed up in the community by general practitioners without definite diagnosis, representing a challenge to identify patients at risk of significant fibrosis who might benefit from an early specific intervention. Accurate fibrosis assessment by primary care or non-hepatologists physicians is limited by a reliance on liver function tests, which correlate poorly with fibrosis, and limited access to discriminatory fibrosis tests. Thus, current management strategies are inefficient in identifying subjects for specialist referral. Patients with mild disease are often referred for NAFLD specialist review when instead the appropriate preventative interventions of lifestyle changes can be delivered effectively in primary care. Conversely, patients with advanced fibrosis or cirrhosis who will benefit from NAFLD specific interventions, including clinical trials and cirrhosis surveillance, often remain undetected until they present with complications of cirrhosis, including hepatocellular carcinoma. This ineffective management contributes to the poor outcomes associated with liver disease and the increasing trends in NAFLD- related morbidity and mortality.

NASH-PI aims to improve the management of NAFLD patients by non-hepatologist physicians through the development of a new specific stepwise NAFLD algorithm following an ETC (Education, tools and communication) process that will be based on:

1. The development of new care pathways based on different combinations of non-invasive tests that facilitate the derivation of diabetic patients from endocrine and primary care units to specialised liver disease units.
2. Peer-to-peer sessions with primary care physicians and diabetologists to discuss the techniques and methods available to screen and detect diabetic patients at risk of developing NAFLD-related significant fibrosis.
3. The implementation of easy and ready to use tools, like an automatic calculation of fNITs in central labs, to allow non-hepatologist physicians detect more efficiently diabetic patients at risk of significant fibrosis.

This proposal will focus on diabetic patients to test the feasibility and accuracy of these diagnostic strategies in a close circuit from primary care and diabetic clinics to NAFLD specialized Units (NSU). Our main goal is to create a NAFLD continuum of care that improves the selection of patients with fibrosis and cirrhosis for referral to secondary care, reducing unnecessary referrals, enhancing the use of healthcare resources with immediate cost-savings, and improving patient experiences by avoiding unnecessary clinic appointments and tests. NASH-PI will improve the identification of NAFLD in diabetic patients to allow for management according to current standard of care and impact on the disease course, helping to reduce NAFLD-related morbidity and mortality and delivering more efficient patient-centered care.

Eligibility criteria: Inclusion Criteria:

1. Age between 18 and 75.
2. Type 2 Diabetes Mellitus. Patients will be considered as diabetic when: A1C ≥6.5% OR FPG ≥126 mg/dL OR 2-h PG ≥200 mg/dl during the OGTT OR anti-diabetic drug users.

Exclusion Criteria:

1. Significant alcohol intake (\>30 g daily for men and \>20g daily for women).
2. Evidence of concomitant liver disease (i.e., viral or autoimmune hepatitis, HIV, drug-induced fatty liver, hemochromatosis, or Wilson's disease).

Primary outcomes:
measure: Accuracy on referral rate
timeFrame: Up to 6 months
Secondary outcomes:
measure: Cut-off scores for fibrosis non-invasive tests (fNITs)
timeFrame: 3 months
measure: Cut-off score for Hepamet Fibrosis Score (HFS) + Transient Elastography (TE)
timeFrame: 3 months
measure: Evaluation of quality-adjusted life years (QALYs)
timeFrame: 9 months
measure: Evaluation of Incremental Cost-Effectiveness Ratios (ICERs)
timeFrame: 9 months
measure: Patient reported diet habits
timeFrame: 6 months
measure: Patient reported physical activity
timeFrame: 6 months
measure: Patient reported individual functioning
timeFrame: 6 months
Other outcomes:
Locations:
city: Düsseldorf
country: Germany
facility: University Hospital Düsseldorf
city: Mainz
country: Germany
facility: University Medical Center Mainz
city: Athens
country: Greece
facility: Harokopio University of Athens
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío de Sevilla
Study officials:
affiliation: Hospital Universitario Virgen del Rocío de Sevilla
name: Manuel Romero-Gómez
role: PRINCIPAL_INVESTIGATOR
References: