Non-Invasive MASLD Diagnosis & T2D Remission Biomarkers

NCT07172997 | Active Not Recruiting DMC

• 2 other identifiers: 559 / 06-Dec-2024RMS-KHUH /IRB/ 2024-788
• Study Type: observational
• Target: 163
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this observational study is to prospectively develop and validate a non-invasive scoring system based on metabolic markers, proteomic, and transcriptomic profiles to accurately screen, diagnose, stage, and monitor Metabolic dysfunction-associated steatotic liver disease (MASLD) activity and regression as a replacement for the invasive liver biopsy tool in Bahraini bariatric patients. The study also aims to identify biomarkers for predicting type 2 diabetes mellitus remission post-bariatric surgery. The main questions it aims to answer are:

• What proteomic and transcriptomic markers can be used to accurately screen, diagnose, stage, and monitor MASLD activity and regression?
• What transcriptomic markers can predict type 2 diabetes mellitus remission? Researchers will compare the proteomic and transcriptomic profiles of bariatric patients before and after surgery to identify molecular changes associated with weight loss and normalization of metabolic biomarkers. The data will be used to design and validate a scoring system for MASLD diagnosis and monitoring. Participants will undergo comprehensive assessments, including anthropometric measurements, metabolic biomarker evaluations, proteomic, and transcriptomic profiling at three time points: before surgery, and at 6- and 12-months post-surgery. The data collected will inform the development of the non-invasive scoring system, which will be tested for its reliability and accuracy in replacing liver biopsy as the standard diagnostic tool for MASLD.

Conditions

MASLD; T2DM (Type 2 Diabetes Mellitus); Non-alcoholic Fatty Liver Disease (NAFLD); Obesity

Keywords

metabolic biomarkers; MASLD proteomics; MASLD transcriptomics; T2DM Transcriptomics; liver biopsy; proteomic biomarkers; transcriptomic biomarkers; bariatric surgery; non-invasive scoring system; shear wave elastoghraphy; Middle East population; Metabolic biomarker evaluation; Anthropometric measurements; Transcriptome profiling; Diagnostic tools; MASLD; Metabolic dysfunction associated liver disease; T2D; T2DM; Type 2 Diabetes Mellitus; NAFLD; Obesity; Non-alcoholic fatty liver disease

Outcome Measures

Primary Outcomes (4)

• Accuracy of Non-invasive Ultrasonography Tools for MASLD Assessment

  To assess the diagnostic accuracy of three ultrasonography tools for diagnosing MASLD by calculating their sensitivity (%), specificity(%), positive predictive value (PPV)(%), and negative predictive value (NPV)(%) compared to the liver histopathology diagnosis: * Conventional Ultrasonography: Detects liver steatosis and evaluates liver size (cm), texture, and fibrosis. * Shear-wave elastography (SWE): Measures liver stiffness(kPa), correlating with fibrosis severity (F0-F1: 0.0 - 8.27 kPa = Normal-mild, F2: 8.27 - 9.4 kPa = mild-moderate, F3: 9.4-11.8 kPa = moderate-severe, F4: \>11.8 kPa cirrhosis). * Ultrasound-guided acoustic pulse (UGAP) examination: Combines ultrasound with acoustic pulses to assess liver steatosis by measuring the attenuation of ultrasound waves as they pass through the liver. Higher attenuation values generally correlate with a greater degree of hepatic steatosis (attenuation coefficient cutoff value (dB/cm/MHz): ≥S1= 0.65, ≥S2= 0.71, S3= 0.77).

  At Baseline, at 6-months after the surgery, and at 12 months after the surgery

• Proteomic Changes and Their Correlation with MASLD Regression

  This outcome measures changes in protein expression between MASLD-positive patients and a control of MASLD- negative patients. Both group will have equal number of participants, and equal male to female ratio. Protein levels will be measured using liquid chromatography tandem mass spectrometry (counts per second (cps), and Changes in protein levels and will be quantified as percent and fold changes. .

  At Baseline

• Accuracy of Available Formulae for MASLD Assessment

  To evaluate the diagnostic accuracy of three formulae for diagnosing MASLD by assessing Sensitivity(percentage), Specificity(percentage), Positive Predictive Value (PPV)(percentage), and Negative Predictive Value (NPV)(percentage) compared to the liver histopathology diagnosis. 1. APRI: Uses AST levels (U/L) and platelet count (x10\^9/l) to estimate liver fibrosis risk (\< 0.5 = minimal or no fibrosis, 0.5 - 1.5 = Moderate fibrosis, \> 1.5 = Severe fibrosis or cirrhosis). 2. FIB-4: Combines age(years), AST(U/L), ALT(U/L), and platelet count (x10\^9/l) to assess liver fibrosis risk (\< 1.45 = minimal or no fibrosis, 1.45 - 3.39 = significant fibrosis, ≥ 3.4 = advanced fibrosis or cirrhosis). 3. NAFLD-Fibrosis Score: Uses age (years), BMI (kg/m\^2), diabetes status, liver enzymes (U/l), platelet count (x10\^9/l), and albumin (g/L) to assess fibrosis risk (\< -1.455 = low probability of fibrosis, -1.455- 0.765 = significant fibrosis, \> 0.675 = high probability of fibrosis).

  At Baseline, at 6-months after the surgery, and at 12 months after the surgery

• mi-RNA Changes and Their Correlation with MASLD Regression and Diabetes Remission

  This outcome measures changes in circulating microRNA (miRNA) levels, in relation to diabetes remission post-bariatric surgery. Changes in miRNA levels will be quantified as percent and fold changes. miRNA levels will be measured using micro-array technique. Changes will be assessed in the diabetic disease state and after achieving diabetes remission, defined by fasting glucose \<100 mg/dL and HbA1c \<6.5%. miRNA changes will be correlated with diabetes remission at 6 and 12 months.

  At Baseline, at 6-months after the surgery, and at 12 months after the surgery

Secondary Outcomes (4)

• Percentage of MASLD Regression Post-Bariatric Surgery

  At 6-months after the surgery, and at 12 months after the surgery

• Percentage of Type 2 Diabetes Remission Post-Bariatric Surgery

  At 6-months after the surgery, and at 12 months after the surgery

• Excess Weight Loss (EWL) Measurement

  At Baseline, at 6-months after the surgery, and at 12 months after the surgery

• Body Composition Parameters After Bariatric Surgery

  At baseline, and at 6 months and 12 months after bariatric surgery

Other Outcomes (1)

• Identification of Novel Biomarkers through Fold Change Analysis and Regression Models

  Through study completion, an average of 1 year

Study Arms (1)

MASLD metabolic biomarker

Adult obese patients (18 years old and above) who underwent bariatric surgery in KHUH surgery department from January 2025 to December2025.

Procedure: Bariatric Surgery

Interventions

Bariatric Surgery PROCEDURE

A surgical procedure used to manage obesity and obesity-related conditions.

Also known as: Sleeve Gastrectomy, Roux-en-Y, Metabolic Surgery, One Anastomosis Gastric Bypass, Biliopancreatic Diversion, Gastric Bypass, Mini-Bypass, OAGB, SAGB, SG

MASLD metabolic biomarker

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Bahraini adult obese patients

You may qualify if:

• Adult obese patients undergoing bariatric surgery in KHUH surgery department consented to be included in the study.

You may not qualify if:

• Patients fail to complete the surgery due to intra-operative complications.
• Patients fail to retrieve liver biopsy sample from due to intra-operative difficulties.
• Patients with missing data pre-operatively
• Body Mass Index less than 30 kg/m2.
• Post-liver transplant patients
• Patients known to have any liver disease other than MASLD
• Patients with history of Alcohol Drinking.

Sponsors & Collaborators

• Royal College of Surgeons in Ireland - Medical University of Bahrain: lead
• King Hamad University Hospital, Bahrain: collaborator
• King Faisal Specialist Hospital & Research Center: collaborator
• King Fahad Medical City: collaborator

Study Sites (2)

Alhakeem Radiology Center

Manama, Manama, 2901, Bahrain

Location

King Hamad University Hospital

Al Muharraq, Muharraq, Bahrain

Location

Related Publications (18)

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Biospecimen

Retention: SAMPLES WITHOUT DNA

5 ml of centrifuged serum blood sample will be retained. liver biopsy sample

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Non-alcoholic Fatty Liver Disease; Obesity

Interventions

Bariatric Surgery; Anastomosis, Roux-en-Y; Biliopancreatic Diversion; Gastric Bypass

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bariatrics; Obesity Management; Therapeutics; Surgical Procedures, Operative; Anastomosis, Surgical; Digestive System Surgical Procedures; Biliary Tract Surgical Procedures; Gastroenterostomy

Study Officials

• John Flood

  RCSI-MUB

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2025
• First Posted: September 15, 2025
• Study Start: January 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: September 15, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Data will be collected in the case report form to allow for cross referencing to check validity. Study documents (paper) will be retained in a secure (kept locked when not in use) location during and after the trial has finished. All essential documents including source documents will be retained for a period of 5 years after study completion (last patient, last study point).
• Access Criteria: Study documents (paper) will be retained in a secure (kept locked when not in use) location during and after the trial has finished.

Locations

BA (2)