Breath Analysis Using an Electronic Nose in Non Alcoholic Fatty Liver Disease

Completed

• Conditions: Non-alcoholic Fatty Liver Disease
• Interventions: Device: Breath analysis - electronic signature "Breath-print"

• Registration Number: NCT02950610
• Lead Sponsor: University of Edinburgh

Brief Summary

The purpose of this is to analyse human exhaled breath by means of a device called electronic nose(eNose) in patients with non-alcoholic fatty liver disease (NAFLD) as a way to non-invasive assessment of liver disease.This device is medically adapted and clinically validated in patients with lung conditions.

Detailed Description

Human exhaled breath contains over 3000 volatile organic compounds (VOCs) that vary in relative concentration in health and disease. Metabolic disorders affecting the liver, such as NAFLD, produce disproportionate organic compounds produced as a by-product of metabolism and thus expired in exhaled breath, excreted in urine and detectable in blood. NAFLD prevalence is increasing and has reached epidemic proportions affecting 90% of obese adults and 22%-53% of obese children.Liver biopsy is the gold standard in diagnosing NAFLD, but it is unpleasant and can lead to complications. There is an unmet need to develop a non-invasive method of assessing liver disease. Comon Invent (Delft, Netherlands) together with the respiratory department at the Amsterdam Medical Centre (AMC), University of Amsterdam, have adapted the electronic nose known as SpiroNose as a prototype device for clinical use. Sensitive electronic sensors detect molecules in breath and generate signals. Complex algorithms and analytical technics allow pattern recognition of breath samples from different subjects. Well charaterised patients will be selected into clinical categories of non-alcoholic fatty liver disease with and without cirrhosis and be compared with healthy individuals.

Edinburgh will be the only site conducting this study. In addition to exhaled breath analysis, blood and urine will be collected to study the end products of metabolism.Furthermore, stool and urine collected from some subjects will be analysed to understand the role of gut bacteria in fermentation, metabolic products as a result cause VOC production.

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-01-13
• Status Verified: 2016-10
• Study First Submitted QC: 2016-10-27
• Study First Posted: 2016-11-01
• Primary Completion: 2017-08
• Study Completion: 2018-05
• Last Update Submitted: 2018-06-21
• Last Update Posted: 2018-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

• Healthy individuals with no known or self declared medical illness with BMI (body mass index) within normal range (18.5-25)
• Non alcoholic fatty liver disease without cirrhosis
• Compensated (no evidence of ascites, encephalopathy) NAFLD cirrhosis; assessed by scoring system - Child's Pugh

Exclusion Criteria

• Ongoing or recent (within last 6months) alcohol consumption more than 21 units per week for males and 14 units per week for females.
• BMI > 40
• Chronic respiratory disease e.g. Chronic obstructive pulmonary disease (COPD), asthma, interstitial fibrosis
• Use of antibiotics within last 4 weeks of sample collection and inflammatory bowel disease, irritable bowel syndrome, celiac sprue, or other chronic inflammatory diseases of the intestines (for intestinal microbiome analysis)
• Other known liver disease e.g. Primary Biliary Cholangitis/cirrhosis (PBC), Alcoholic liver disease (ALD), Autoimmune and hepatitis
• Inability to provide informed consent.
• Participation in other clinical intervention/drug trial

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Nonalcoholic steatohepatitis	Breath analysis - electronic signature "Breath-print"	NAFLD without cirrhosis: Metabolic syndrome with known liver disease (NAFLD, excluding other coexisting liver condition) without cirrhosis
NAFLD Cirrhosis	Breath analysis - electronic signature "Breath-print"	NAFLD cirrhosis: well characterised NAFLD compensated cirrhosis (Child's A-B)
Healthy	Breath analysis - electronic signature "Breath-print"	Healthy volunteer: self-declared healthy individual (no known illness or medications) with Normal BMI

Primary Outcome Measures

Name	Time	Method
Characterisation of exhaled breath composition	12 months	Molecular characterisation of breath volatile organic compounds through Gas Chromatography and Mass Spectrometry
Characterise the electronic signature "breath-print" in pre-defined cohorts	12 months	Identify disease specific electronic nose wave pattern

Secondary Outcome Measures

Name	Time	Method
Profiling intestinal microbiome and assessing end-metabolic products in urine	12 months	Demonstrate dysbiosis in stool microbial and characterise metabolic products in urine of cohorts studied

Trial Locations

Locations (1)

Clinical Research Facility - Wellcome Trust, Royal Infirmary Site; 🇬🇧 Edinburgh, Midlothian, United Kingdom