NASH Patient's Itinerary: Comparison of Strategies for Screening, Referring and Management of Diabetic Patients

NCT06688149 | Completed

• 1 other identifier: NASH-PI
• Study Type: interventional
• Target: 536
• Locations: 3 countries
• Sites: 4

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.

Conditions

Non-alcoholic Fatty Liver Disease (NAFLD)

Keywords

NAFLD; MASLD; NASH; MASH; FIBROSIS; NITs; TRANSIENT ELASTOGRAPHY; FIB4; NFS; HFS; DIABETES

Outcome Measures

Primary Outcomes (1)

• Accuracy on referral rate

  To determine the accuracy on referral rate for diabetic patients at risk of advanced fibrosis using each of the strategies under study, and determine the sensitivity, specificity, PPV, NPV, likelihood ratios and overall accuracy of each of them.

  Up to 6 months

Secondary Outcomes (7)

• Cut-off scores for fibrosis non-invasive tests (fNITs)

  3 months

• Cut-off score for Hepamet Fibrosis Score (HFS) + Transient Elastography (TE)

  3 months

• Evaluation of quality-adjusted life years (QALYs)

  9 months

• Evaluation of Incremental Cost-Effectiveness Ratios (ICERs)

  9 months

• Patient reported diet habits

  6 months

Study Arms (3)

Arm A: Current management of NAFLD patients in daily clinical practice

EXPERIMENTAL

It will be taken as a reference for comparisons and will include the diagnosis and referral criteria that have been used the two previous years. CONSTANTS, a study included in the EPOS European Project has already allowed us to approach the burden of this entity in clinical practice in two sites of this consortium (Mainz and Sevilla). An overall analysis will be conducted to harmonize current standard of care (Arm A) in our centres. The case records of all patients referred with a diagnosis of NAFLD will be reviewed and evaluated for evidence of advanced fibrosis/cirrhosis based on a composite of history, physical examination, imaging, transient elastography, and liver histology when available. HFS, NFS, and FIB-4 scores will be calculated, and patients with a priori low-risk of advanced fibrosis will be deemed to have no evidence of liver fibrosis and thus referred inappropriately.

Diagnostic Test: Derivation algorithms

Arm B: Combination of blood-based non-invasive tests (HFS, NFS, and FIB-4)

EXPERIMENTAL

Patients will be assigned with the following scores: 1. 0 points if the value is under the lower cut-off (HFS \<0.12; NFS\<-1.455; FIB-4 \<1.30); 2. 1 point if the value is allocated in the grey zone (HFS 0.12-0.47; NFS -1.455-0.676; FIB-4 1.30-2.67); 3. 2 points if the value is above the higher cut-off (HFS \>0.47; NFS \>0.676; FIB-4 \>2.67). We will determine the optimal cut-offs (between 0 and 6 points) for keeping patients in non-specialized units or referring them to NSUs. * Age corrected threshold should be implemented in patients older than 65 years in NFS (from -1.455 to 0.12) and FIB-4 (from 1.30 to 2.00).

Diagnostic Test: Derivation algorithms

Arm C: Combination of HFS and TE

EXPERIMENTAL

Patients will be classified using the blood-based non-invasive tests to determine the HFS and a transient Elastography (TE). Patients with a HFS score of \> 0.12 or TE \>8 kPa for both M and XL probe should be classified as patients with an intermediate-to-high risk of advanced fibrosis and will be referred to a specialist.

Diagnostic Test: Derivation algorithms

Interventions

Derivation algorithms DIAGNOSTIC_TEST

Derivation algorithm based on non-invasive methods, to standardise the continuum of care for diabetic patients with NAFLD from primary care and endocrinology settings to NAFLD specialised units (NSU)

Arm A: Current management of NAFLD patients in daily clinical practice; Arm B: Combination of blood-based non-invasive tests (HFS, NFS, and FIB-4); Arm C: Combination of HFS and TE

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 75.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Fundación Pública Andaluza para la gestión de la Investigación en Sevilla: lead
• Gilead Sciences: collaborator
• Barcelona Institute for Global Health: collaborator
• Harokopio University: collaborator
• University Medical Center Mainz: collaborator
• University Düsseldorf: collaborator

Study Sites (4)

University Hospital Düsseldorf

Düsseldorf, Germany

Location

University Medical Center Mainz

Mainz, Germany

Location

Harokopio University of Athens

Athens, Greece

Location

Hospital Universitario Virgen del Rocío de Sevilla

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fibrosis; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Manuel Romero-Gómez

  Hospital Universitario Virgen del Rocío de Sevilla

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2024
• First Posted: November 14, 2024
• Study Start: January 31, 2021
• Primary Completion: January 31, 2023
• Study Completion: January 8, 2024
• Last Updated: November 14, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); GR (1); DE (2)