Non-alcoholic Fatty Liver DiseaseBENNCT02950610
Breath Analysis Using an Electronic Nose in Non Alcoholic Fatty Liver Disease
An observational study of Non-alcoholic Fatty Liver Disease, run by University of Edinburgh at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease
- What is being tested?
- Breath analysis - electronic signature "Breath-print"
- Type of treatment
- Medical device
- How many people
- 90 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2016to May 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: All eligible patients will have to consent to the study. The study population will consist of participants aged between 18 and 75 years old in the following cohorts (Healthy individuals, Non-alcoholic steatohepatitis (non-cirrhotic) and compensated Non-alcoholic liver cirrhosis). Each cohort will have 30 patients. There will be an equal number of participants for the healthy control group. In summary, the investigators aim to recruit 30 subject in the patient cohorts and 30 in healthy, totaling a number of 90 in the study
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Clinical Research Facility - Wellcome Trust, Royal Infirmary Site
Edinburgh, Midlothian, EH16 4SA
About this study
Official title: Breath Analysis Using an Electronic Nose in Non Alcoholic Fatty Liver Disease (BEN) Study
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.
Read the 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.
- Conditions
- Non-alcoholic Fatty Liver Disease
- Being tested
- Breath analysis - electronic signature "Breath-print"
- Keywords
- Electronic nose, Non invasive diagnosis of NAFLD, NAFLD, exhaled breath analysis, Volatile organic compounds
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Breath analysis - electronic signature "Breath-print"Device
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.
| Study group | Role | What they receive |
|---|---|---|
| Healthy | Healthy volunteer: self-declared healthy individual (no known illness or medications) with Normal BMI Receives: Device: Breath analysis - electronic signature "Breath-print" | |
| Nonalcoholic steatohepatitis | NAFLD without cirrhosis: Metabolic syndrome with known liver disease (NAFLD, excluding other coexisting liver condition) without cirrhosis Receives: Device: Breath analysis - electronic signature "Breath-print" | |
| NAFLD Cirrhosis | NAFLD cirrhosis: well characterised NAFLD compensated cirrhosis (Child's A-B) Receives: Device: Breath analysis - electronic signature "Breath-print" |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterise the electronic signature "breath-print" in pre-defined cohorts
Identify disease specific electronic nose wave pattern
Measured: 12 months
Characterisation of exhaled breath composition
Molecular characterisation of breath volatile organic compounds through Gas Chromatography and Mass Spectrometry
Measured: 12 months
Secondary outcomes (1)
Profiling intestinal microbiome and assessing end-metabolic products in urine
Demonstrate dysbiosis in stool microbial and characterise metabolic products in urine of cohorts studied
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2016 (estimated)
- Study startJan 2016
- Primary completionAug 2017
- Study completionMay 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Non-alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- University of Strathclyde, University of Amsterdam
- Responsible party
- Sponsor
- Investigators
- Peter C Hayes, MD,PhD,FRCPE, Principal investigator, Centre for liver and digestive disorder, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02950610
- Sponsor's protocol ID
- 165914
- Acronym
- BEN
- Status last verified
- Oct 2016
- First submitted
- 13 Jan 2016
- Last updated
- 26 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: Individual participant data will not shared. Participants will be identified as a part of pre-defined cohort as categorised clinically.
Publications
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.
PubMed 24135544de 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.
PubMed 26469298Probert 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.
PubMed 19795029Wu 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.
PubMed 20673359Sinha R, Gillespie SL, Brinkman P, Bassett P, Lockman KA, Jaap AJ, Fallowfield JA, Hayes PC, Plevris JN. Volatomics for Diagnosis and Risk Stratification of MASLD: A Proof-Of-Concept Study. Aliment Pharmacol Ther. 2025 Jul;62(2):180-192. doi: 10.1111/apt.70176. Epub 2025 May 20.
PubMed 40391721Sinha R, Lockman KA, Homer NZM, Bower E, Brinkman P, Knobel HH, Fallowfield JA, Jaap AJ, Hayes PC, Plevris JN. Volatomic analysis identifies compounds that can stratify non-alcoholic fatty liver disease. JHEP Rep. 2020 Jun 15;2(5):100137. doi: 10.1016/j.jhepr.2020.100137. eCollection 2020 Oct.
PubMed 32775974
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Breath Analysis Using an Electronic Nose in Non Alcoholic Fatty Liver Disease (BEN) Study
- ClinicalTrials.gov ID
- NCT02950610
- Acronym / sponsor ID
- BEN / 165914
- Conditions
- Non-alcoholic Fatty Liver Disease
- Keywords
- Electronic nose, Non invasive diagnosis of NAFLD, NAFLD, exhaled breath analysis, Volatile organic compounds
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- University of Strathclyde, University of Amsterdam
- Study start
- Jan 2016 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- May 2018 (actual)
- First posted
- 1 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy | – | Device: Breath analysis - electronic signature "Breath-print"Healthy volunteer: self-declared healthy individual (no known illness or medications) with Normal BMI |
| Nonalcoholic steatohepatitis | – | Device: 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 | – | Device: Breath analysis - electronic signature "Breath-print"NAFLD cirrhosis: well characterised NAFLD compensated cirrhosis (Child's A-B) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- All eligible patients will have to consent to the study. The study population will consist of participants aged between 18 and 75 years old in the following cohorts (Healthy individuals, Non-alcoholic steatohepatitis (non-cirrhotic) and compensated Non-alcoholic liver cirrhosis). Each cohort will have 30 patients. There will be an equal number of participants for the healthy control group. In summary, the investigators aim to recruit 30 subject in the patient cohorts and 30 in healthy, totaling a number of 90 in the study
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Device | Healthy, NAFLD Cirrhosis, Nonalcoholic steatohepatitis |
Primary outcome
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
1 secondary outcome
Profiling intestinal microbiome and assessing end-metabolic products in urine
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2018.
- Results publication: PubMed 24135544Wlodzimirow 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.
- Results publication: PubMed 26469298de 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.
- Results publication: PubMed 19795029Probert 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.
- Results publication: PubMed 20673359Wu 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.
- Derived from this study: PubMed 40391721Sinha R, Gillespie SL, Brinkman P, Bassett P, Lockman KA, Jaap AJ, Fallowfield JA, Hayes PC, Plevris JN. Volatomics for Diagnosis and Risk Stratification of MASLD: A Proof-Of-Concept Study. Aliment Pharmacol Ther. 2025 Jul;62(2):180-192. doi: 10.1111/apt.70176. Epub 2025 May 20.
- Derived from this study: PubMed 32775974Sinha R, Lockman KA, Homer NZM, Bower E, Brinkman P, Knobel HH, Fallowfield JA, Jaap AJ, Hayes PC, Plevris JN. Volatomic analysis identifies compounds that can stratify non-alcoholic fatty liver disease. JHEP Rep. 2020 Jun 15;2(5):100137. doi: 10.1016/j.jhepr.2020.100137. eCollection 2020 Oct.
- Individual participant dataSharing planned: No. Individual participant data will not shared. Participants will be identified as a part of pre-defined cohort as categorised clinically.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter C Hayes, MD,PhD,FRCPE principal investigator
Centre for liver and digestive disorder, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Non-alcoholic Fatty Liver Disease, run by University of Edinburgh at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterise the electronic signature "breath-print" in pre-defined cohorts (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02950610, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2018.