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

Overview

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.

Full Title of Study: “Breath Analysis Using an Electronic Nose in Non Alcoholic Fatty Liver Disease (BEN) Study”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: August 2017

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.

Interventions

  • Device: Breath analysis – electronic signature “Breath-print”
    • Patients and Healthy volunteers ( as defined in 3 cohorts) will breath into disposable, once-use only bacterial filter channeled into electronic device comprising on sensors capable to reacting to organic compounds. Breathing manoeuvre will be simple, non-exertional and relaxed. 2 breathing manoeuvres will be performed and sensor responses will be captured.

Arms, Groups and Cohorts

  • Healthy
    • Healthy volunteer: self-declared healthy individual (no known illness or medications) with Normal BMI
  • Nonalcoholic steatohepatitis
    • NAFLD without cirrhosis: Metabolic syndrome with known liver disease (NAFLD, excluding other coexisting liver condition) without cirrhosis
  • NAFLD Cirrhosis
    • NAFLD cirrhosis: well characterised NAFLD compensated cirrhosis (Child’s A-B)

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • University of Edinburgh
  • Collaborator
    • University of Strathclyde
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Peter C Hayes, MD,PhD,FRCPE, Principal Investigator, Centre for liver and digestive disorder, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA

Citations Reporting on Results

Wlodzimirow KA, Abu-Hanna A, Schultz MJ, Maas MA, Bos LD, Sterk PJ, Knobel HH, Soers RJ, Chamuleau RA. Exhaled breath analysis with electronic nose technology for detection of acute liver failure in rats. Biosens Bioelectron. 2014 Mar 15;53:129-34. doi: 10.1016/j.bios.2013.09.047. Epub 2013 Sep 30.

de Vries R, Brinkman P, van der Schee MP, Fens N, Dijkers E, Bootsma SK, de Jongh FH, Sterk PJ. Integration of electronic nose technology with spirometry: validation of a new approach for exhaled breath analysis. J Breath Res. 2015 Oct 15;9(4):046001. doi: 10.1088/1752-7155/9/4/046001.

Probert CS, Ahmed I, Khalid T, Johnson E, Smith S, Ratcliffe N. Volatile organic compounds as diagnostic biomarkers in gastrointestinal and liver diseases. J Gastrointestin Liver Dis. 2009 Sep;18(3):337-43.

Wu GD, Lewis JD, Hoffmann C, Chen YY, Knight R, Bittinger K, Hwang J, Chen J, Berkowsky R, Nessel L, Li H, Bushman FD. Sampling and pyrosequencing methods for characterizing bacterial communities in the human gut using 16S sequence tags. BMC Microbiol. 2010 Jul 30;10:206. doi: 10.1186/1471-2180-10-206.

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