Genetic Polymorphisms Associated With the Risk of Pancreatitis in Patients With Alcohol Related Cirrhosis.

January 20, 2025 updated by: Institute of Liver and Biliary Sciences, India

Alcohol is a known risk factor for both pancreatitis and cirrhosis. However, not all patients with alcohol related cirrhosis develop pancreatitis. It is not known which patients with alcohol-related cirrhosis develop symptomatic or clinically inapparent pancreatitis (Acute or Chronic Pancreatitis).There is no data whether genetic polymorphisms predispose patients with alcohol-related cirrhosis to additional pancreatic injury. There is no data on the spectrum of clinical and subclinical pancreatic changes (structural and functional) in patients with alcohol-related cirrhosis, and their genotypic correlates.This study aims to determine pancreatitis-related gene variants among patients with alcohol-related cirrhosis, with and without pancreatitis. We also aim to study differences in nutritional and functional parameters among alcoholic cirrhosis with and without chronic pancreatitis and also define the relationship of genetic polymorphisms with the pancreatic phenotype. Consecutive patients with alcohol related cirrhosis will be screened for changes of pancreatitis on CT/MR/EUS. Those with and without pancreatitis will be compared with respect to demographic, clinical, genotype, nutritional status .We will also be including a group of MAFLD/Cryptogenic cirrhosis for genotypic and phenotypic comparison.

Study Overview

Status

Not yet recruiting

Conditions

Alcohol-related Liver Disease

Detailed Description

Aim and Objective - To determine pancreatitis-related gene variants among patients with alcohol-related cirrhosis, with and without pancreatitis.

Primary objective: To determine the genetic variants associated with morphological and functional pancreatic changes among patients with alcohol-related cirrhosis.

Secondary objectives

To define the relationship of genetic polymorphisms with the pancreatic phenotype.*
To study differences in nutritional and functional parameters among alcoholic cirrhosis with and without chronic pancreatitis.

Hypothesis -

- Genetic polymorphisms related to pancreatitis predispose patients with alcohol-related cirrhosis to additional pancreatic injury.

Associated chronic pancreatitis (clinically apparent or subclinical) negatively influences the nutritional and functional status of patients with alcohol-related cirrhosis

Study design: Cross sectional study of two study cohorts
Study period: 1 year.
Sample size with justification: Studies have reported pathogenic SPINK 1 mutations in 25% -50.0% among idiopathic CP and 10-20% in acute pancreatitis as compared to 1%-4.7% among controls. The investigator assume pathogenic SPINK 1 mutation frequency of 50% and 1% among alcohol-related cirrhosis with and without CP, respectively. The investigator also assume a 33% prevalence of CP among alcohol-related cirrhosis. With significance (α) at 0.5, power of 80%, investigator need to enroll 100 patients of alcohol-related cirrhosis.The investigator will also include a cohort of 50 males with cirrhosis of other etiologies.

Study Type

Observational

Enrollment (Estimated)

150

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Dr Aakula Suguna Sree, MD
Phone Number: 01146300000
Email: sugunasreeaakula@gmail.com

Study Contact Backup

Name: Prof. Vikram Bhatia, DM
Phone Number: 01146300000
Email: vikrambhatiadr@gmail.com

Study Locations

India
- Delhi
  - New Delhi, Delhi, India, 110070
    - Institute of Liver & Biliary Sciences (ILBS)
    - Contact:
      
      Dr Aakula Suguna Sree, MD
      
      Phone Number: 01146300000
      
      Email: sugunasreeaakula@gmail.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

Study Population

Patients > 18 years of age.
Who have either alcohol related or non alcohol related cirrhosis.

Description

Inclusion Criteria:

Patients > 18 years of age.
Alcohol-related cirrhosis
Males

Exclusion Criteria:

Current Hepatic encephalopathy or cognitive dysfunction precluding adequate nutritional and functional assessment.
HCC.
Complete or partial PVT.
Significant cardio-pulmonary comorbidity
Patients who do not consent for genetic study
Inability to provide informed consent.
Cannot understand Hindi or English should be excluded since they will not be able to reply objectively to questionnaire.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
Alcohol-related cirrhosis
Liver cirrhosis of other etiologies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Genetic polymorphisms in one or more pancreatitis-associated genes* among patients with alcohol-related cirrhosis, with and without pancreatitis. Time Frame: Day 0	Day 0

Secondary Outcome Measures

Outcome Measure	Time Frame
Differences in genetic polymorphisms in one or more pancreatitis related genes in patients with pancreatitis between alcohol related cirrhosis and cirrhosis of other etiologies. Time Frame: Day 0	Day 0
To define the relationship of genetic polymorphisms with the pancreatic phenotype.* Time Frame: Day 0	Day 0
Prevalence of pancreatitis defined by CT/MR/EUS among patients with alcohol-related cirrhosis. Time Frame: Day 0	Day 0
Difference in prevalence of pancreatitis defined by CT/MR/EUS among patients with alcohol-related cirrhosis and cirrhosis of other etiologies . Time Frame: Day 0	Day 0
Severe exocrine insufficiency defined by fecal elastase <100µg/g stool among cirrhotic patients with and without chronic pancreatitis Time Frame: Day 0	Day 0
Endocrine insufficiency defined by FBS >126mg/dl and HbA1c >6.5% among cirrhotic patients with and without chronic pancreatitis. Time Frame: Day 0	Day 0
Sarcopenia defined by Skeletal muscle index of < 50cm/m2 in men on CT, and/or 7.0 kg/m2 on DEXA among cirrhotic patients with and without chronic pancreatitis. Time Frame: Day 0	Day 0
Liver frailty index > 4.5 Time Frame: Day 0	Day 0

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Liver and Biliary Sciences, India

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 25, 2025

Primary Completion (Estimated)

January 31, 2026

Study Completion (Estimated)

January 31, 2026

Study Registration Dates

First Submitted

January 1, 2025

First Submitted That Met QC Criteria