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

Non-alcoholic Fatty Liver Disease Clinical Trial

— BEN  

Official title:

Breath Analysis Using an Electronic Nose in Non Alcoholic Fatty Liver Disease (BEN) Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02950610
• Other study ID #: 165914
• Status: Completed
• Start date: January 2016
• Est. completion date: May 2018

Study information

• Verified date: October 2016
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: May 2018
• Est. primary completion date: August 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease

Intervention

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.

Locations

Country	Name	City	State
United Kingdom	Clinical Research Facility - Wellcome Trust, Royal Infirmary Site	Edinburgh	Midlothian

Sponsors (3)

Lead Sponsor	Collaborator
University of Edinburgh	University of Amsterdam, University of Strathclyde

Country where clinical trial is conducted

United Kingdom, 

References & Publications (4)

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 — View Citation

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. Review. — View Citation

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: 1 — View Citation

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. 20 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Characterise the electronic signature "breath-print" in pre-defined cohorts	Identify disease specific electronic nose wave pattern	12 months
Primary	Characterisation of exhaled breath composition	Molecular characterisation of breath volatile organic compounds through Gas Chromatography and Mass Spectrometry	12 months
Secondary	Profiling intestinal microbiome and assessing end-metabolic products in urine	Demonstrate dysbiosis in stool microbial and characterise metabolic products in urine of cohorts studied	12 months