MicroRNAs as Bile-based Biomarkers in Pancreaticobiliary Cancers

NCT06258824 | Completed

• 1 other identifier: MIRABILE
• Study Type: observational
• Target: 229
• Locations: 1 country
• Sites: 1

Brief Summary

pancreatic or biliary-tract cancer can be a serious diagnosis, as many patients present too late for surgery. Cancer cells have been found to release small messenger molecules called that regulate cancer genes called microRNAs (miRNAs). The goal of this observational study is to learn about the role of miRNAs from bile and blood samples in patients with pancreatic cancer and bile duct cancer. The main question\[s\] it aims to answer are:

• Can this detect patients presenting with jaundice (yellow-skin) undergoing endoscopy?
• Can this distinguish between the types of cancer? Participants will have blood and bile samples collected prior to diagnosis and their clinical pathway will be followed up for 6 months.

Conditions

Pancreatic Cancer; Cholangiocarcinoma; Ampullary Cancer; Biliary Stricture; Gallstone Disease

Keywords

microRNA; ERCP; biomarker

Outcome Measures

Primary Outcomes (1)

• Diagnostic Value as measured by Area under the Curve (AUC) for candidate miRNAs

  Expression values for each miRNA is calculated and used to undertake Multiple logistic regression was undertaken for candidates individually and in combination using GraphPad Prism. Data was prepared as a binary outcome and all main effects are included in the model. Optimum cut-offs were determined using thresholds obtained from the ROC curve at the maximum Youden index. Youden's J statistic (also called Youden's index) is a single statistic that ranges from 0 to 1 and is determined by the formula (Specificity + Sensitivity -1). Where multiple hypotheses were tested, an appropriate Benjamini-Hochberg (False Discovery Rate) correction was applied to give an adjusted p-value. A p (adjusted) value of \<0.05 was considered to be statistically significant.

  On the day of ERCP

Study Arms (3)

Pancreatic Cancer (PDAC)

A clinical diagnosis of PDAC was defined by results of a multidisciplinary team meeting consisting of at least a consultant hepatopancreaticobiliary surgeon, consultant hepatopancreaticobiliary physician, consultant histopathologist and consultant radiologist. ERCP findings, endoscopic ultrasound findings, biliary brushing cytology, and fine needle aspiration cytology were anonymised and recorded. The combination of a pancreatic mass on radiographic imaging without acute cholangiopathy, and clinical or radiographic progression after ≥12 months of follow-up, or death clinically and radiographically determined to be due to pancreatic cancer. For surgical resection and biopsy specimens, diagnoses and staging were rendered based on standard histo-morphological criteria. For the purposes of analysis, pathological staging was used in preference to clinical staging where possible.

Diagnostic Test: Small RNA Sequencing and Validation of candidate miRNAs

Cholangiocarcinoma (CCA)

A clinical diagnosis of CCA was defined by radiological criteria according to results of a multidisciplinary team meeting consisting of at least a consultant hepatopancreaticobiliary surgeon, consultant hepatopancreaticobiliary physician, consultant histopathologist and consultant radiologist. ERCP findings, endoscopic ultrasound findings, biliary brushing cytology, and fine needle aspiration cytology were anonymised and recorded. This was also determined based on clinical or radiographic progression after ≥12 months of follow-up, or death clinically and radiographically determined to be due to cancer. For surgical resection and biopsy specimens, diagnoses and staging were rendered based on standard histo-morphological criteria. For the purposes of analysis, pathological staging was used in preference to clinical staging where possible.

Diagnostic Test: Small RNA Sequencing and Validation of candidate miRNAs

Benign

A clinical diagnosis of benign disease was defined by assessment at ERCP as well as results of a multidisciplinary team meeting consisting of at least a consultant hepatopancreaticobiliary surgeon, consultant hepatopancreaticobiliary physician, consultant histopathologist and consultant radiologist. Any patients with a benign aetiology were either clinically determined on the basis of no further progression after ≥12 months follow-up with either documented resolution or stability of prior ductal abnormalities or no further intervention as documented in electronic hospital records at 12 months.

Diagnostic Test: Small RNA Sequencing and Validation of candidate miRNAs

Interventions

Small RNA Sequencing and Validation of candidate miRNAs DIAGNOSTIC_TEST

Samples were prepared for small RNA sequencing using Qiagen's QIAseq small RNA Library Prep kit, quality controlled using an Agilent Bioanalyzer 2100 and sequenced on an NextSeq 500 system (Illumina, San Diego, USA) using the default single-end 75 base pair protocol to include integrated unique molecular indices (UMIs). Validation was undertaken using Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) either using target-specific stem-loop primer assays (TaqMan) or universal reverse transcription (RT) and locked nucleic acid (LNA) enhanced specific primers with SYBR green I assay detection

Benign; Cholangiocarcinoma (CCA); Pancreatic Cancer (PDAC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients (\>18 years old) undergoing ERCP for benign and malignant pancreatico-biliary disease/strictures.

You may qualify if:

• Age ≥ 18 years.
• Scheduled for clinical reason to undergo an ERCP (endoscopic retrograde cholangiopancreatography).
• WHO performance status 0, 1 or 2.
• Willing and mentally able to provide written informed consent.
• Suspected of having benign pancreaticobiliary disease (e.g. chronic pancreatitis, primary sclerosing cholangitis, common bile duct gallstones (choledocholithiasis), sphincter of Oddi dysfunction); or suspected of having PDAC or BTC.
• Presenting with obstructive jaundice and/or an indeterminate biliary stricture.

You may not qualify if:

• Age \<18years old.
• Patients undergoing ERCP post-bariatric surgery, hepatico-jejunostomy or Bilroth II .
• Pregnancy.
• WHO performance status 3 or 4.
• Not willing or able to sign informed consent.
• Not scheduled for endoscopic procedures for clinical reasons.
• No clinical or image data suggestive of pancreaticobiliary disease and need for endoscopic intervention or investigation.

Sponsors & Collaborators

• Imperial College London: lead
• Royal Surrey County Hospital NHS Foundation Trust: collaborator
• Royal Free Hospital NHS Foundation Trust: collaborator

Study Sites (1)

Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Bile and blood plasma.

MeSH Terms

Conditions

Pancreatic Neoplasms; Cholangiocarcinoma; Cholelithiasis

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Biliary Tract Diseases

Study Officials

• Adam E Frampton, MB BS FRCS PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 6, 2024
• First Posted: February 14, 2024
• Study Start: January 1, 2018
• Primary Completion: March 11, 2020
• Study Completion: July 27, 2020
• Last Updated: February 14, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)