Non-invasive Tests for Non-alcoholic Steato-hepatitis (TEIRESEAS)

Non-invasive Blood Tests for the Diagnosis and Therapeutic Monitoring of Non-alcoholic Steato-hepatitis

The main objective is to study and validate a new approach for NASH and liver fibrosis diagnosis and personalized follow-up based on monocyte biomarkers and plasma metabolites. The investigators will assess if PLIN2 and RAB14 can be used not only to identify subjects with NASH and advanced fibrosis but also for monitoring the effect of treatment alone or in combination with other metabolic parameters

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity; Diabete Type 2; NASH With Fibrosis
• Intervention / Treatment: Procedure: Administration of Deuterated water

• Study Type: Interventional
• Enrollment (Estimated): 828
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Policlinico Universitario Agostino Gemelli IRCCS: Subjects with NASH documented by liver biopsy or fibroscan and no evidence of another form of liver disease with a BMI ≥ 30 and ≤40 kg/m2. Age 25-65 years.
• Coorte Azienda Ospedaliera Mater Domini: subjects with NASH documented by liver fibroscan aged >40 years with one or more cardiovascular risk factors,including overweight/obesity, elevated blood pressure, dyslipidemia, and dysglycemia
• Azienda Ospedaliero-Universitaria Policlinico Federico II: Subjects with NASH documented by fibroscan and no evidence of another form of liver disease. Age 25-65 years.

Exclusion Criteria:

• All units: Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous 6 months; Liver cirrhosis; End stage renal failure; Participation in any other concurrent therapeutic clinical trial; Any other life-threatening, non-cardiac disease; Pregnancy; Inability to give informed consent; Substantial alcohol consumption (>20 g/day for women or >30 g/day for men); Wilson's disease; Lipodystrophy; Parenteral nutrition; Abetalipoproteinemia; Interfering medications (e.g., amiodarone, methotrexate, tamoxifen, corticosteroids).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deuterated Water; Subjects, enrolled by Operative Federico II University, will be asked to drink the evening before the study 3 mg/kg of deuterated water (2H2O). A blood sample will be taken the morning after an overnight fast and after consuming 2H2O.	Procedure: Administration of Deuterated water; A blood sample will be taken in the morning after an overnight fast and after consuming deuterated water (2H2O) (3 g/kg body water) the evening before the study day to achieve a plasma water enrichment of 0.3% for the measurement of DNL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of NASH and Advanced Fibrosis, using PLIN2 and RAB14, in 288 patients undergoing bariatric surgery	PLIN2 and RAB14 will be assessed by flow cytometry in monocytes stored at -80°C from all patients who participated in the BRAVES RCT (288 Subjects). PLIN2 and RAB14 median fluorescent intensity will be used to identify subjects with NASH (NAS >=4) and advanced fibrosis (stage>=2).	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of PLIN2 and RAB14 with non-invasive test for the detection of NASH with significant fibrosis in the CATAMERIS cohort (500 subjects).	500 Subjects from the CATAMERIS cohort will undergo the following analysis: Transient elastography; Blood sampling for the evaluation of non-invasive score (FIB4, APRI and FNI); Monocyte isolation for PLIN2 and RAB14 assessment by flow cytometry; Plasma sample collection for metabolomic and lipidomic analysis. PLIN2 and RAB14 accuracy will be compared to Transient elastography, FIB4, APRI and FNI for the dectection of NASH with significant fibrosis	18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Understanding the mechanisms underlying the formation, regulation, and metabolism of lipid droplets in the pathogenesis of NAFLD in 40 subjects with NAFLD with or without fibrosis.	40 subjects with NAFLD with or without fibrosis, assessed with fibroscan, will be asked to drink 3 mg/kg of deuterated water the evening before the study. The following analysis will be performed after the administration of deuterated water : PLIN2 and RAB14 will be assessed by flow cytometry in monocytes Metabolomic and lipidomic analysis will be performed in plasma samples	18 months

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Collaborators: Federico II University; Azienda Ospedaliera Universitaria Mater Domini, Catanzaro; National Research Council, Institute of Clinical Physiology, Italy
• Investigators: Principal Investigator: Geltrude Mingrone, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2024
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: July 18, 2024
• First Submitted That Met QC Criteria: March 27, 2026
• First Posted (Actual): March 31, 2026

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Diabetes Mellitus, Type 2
• Other Study ID Numbers: PNRR-MCNT2-2023-12377036

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No