Liver FibrosisNCT05935488
Early Liver Disease Breath Detection
An observational study of Liver Fibrosis and NASH, run by Owlstone Ltd at 1 site in United Kingdom.
Trial summary
The Early Liver Disease Breath Detection Study is a cross-sectional study where subjects with advanced liver fibrosis will ingest a mixture of food-grade compounds (known as Exogenous Volatile Organic Compound or EVOCs) in the form of an emulsion and then provide multiple breath samples. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Fibrosis, NASH, Liver Diseases
- What is being tested?
- EVOCs emulsion
- How many people
- 1 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 21 May 2024to 12 Dec 2024
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: A total of 30 subjects with fibroscan confirmed liver fibrosis likely due to NASH will be recruited. To be eligible for the study participation, subjects must meet the inclusion and exclusion criteria.
Who may be able to join
- Able to provide written informed consent.
- >18 years old.
- Body weight > 50 kg.
- Alcohol consumption - does not drink to excess (>30 g/day in men, >20 g/day in women).
- Fibroscan kilopascal (kPa) between 8.5 and 13.5 within 6 months and/or a liver biopsy within the last 3 years showing a fibrosis activity score ≥ F2 and a NAS score > 4 with a diagnosis of non alcoholic steatohepatitis (NASH)
Who cannot join
- (Anticipated) inability to complete the breath sampling procedure due to e.g. inability to maintain adequate ventilation unaided or claustrophobia / Inability to comply with the study procedures in the opinion of the investigator.
- Participant has cirrhosis.
- Participant has current hepatocellular carcinoma (HCC) or currently being treated for HCC. Those previously with/treated for and now clear of HCC can be recruited.
- Participant's cause of liver disease is known to be one of alcohol abuse, hepatitis, autoimmune hepatitis, medications, haemochromatosis, alpha1 antitrypsin deficiency, Wilson disease, biliary problems.
- Presence of current common cold or any other infectious disease including any recent symptoms of Covid-19.
- Participant is known to be pregnant or breast feeding.
Show all 9Show fewer
- Participant with a diagnosis of chronic, active gastritis
- Participant is affected by asthma, chronic obstructive pulmonary disease (COPD), and/or airway hyperactivity.
- Known intolerances and/or allergies (*) to any food containing tested compounds. For limonene, citrus fruits, and fruit juices. For benzyl alcohol, apricots, cranberries, and cocoa. For 2-pentanone cheddar cheese, ripe bananas, and defatted soybean flour. For 2-butanol cheddar cheese and yogurt. For nonanal, apple, avocado, black currants, cooked beef, cucumber, fish, grapefruit, lemon, lime, mandarin, orange, and peach.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
North Norfolk Primary Care
Norwich, Norfolk, NR11RB
About this study
Official title: Breath Detection of Non-alcoholic Steatohepatitis (NASH)-Induced Metabolic Alterations Using Food Flavors.
The Early Liver Disease Breath Detection Study is a cross-sectional study where subjects with advanced liver fibrosis will ingest a mixture of food-grade compounds (known as Exogenous Volatile Organic Compound or EVOCs) in the form of an emulsion and then provide multiple breath samples. These EVOCs can be measured on exhaled breath and it has been found that liver diseases can affect the way EVOCs are processed in the body. The objective is to identify if changes in the way these EVOCs are processed in the body can have the potential to diagnose early stage liver diseases for these subjects. Subjects with fibro-scan confirmed fibrosis will be recruited from Norfolk and Norwich University Hospital (NNUH) by local research staff, they will be invited to take part in the study at a dedicated clinic at OneNorwich Practises a clinic based in Norwich City Centre. They will be asked to fast overnight then provide a baseline breath sample, before ingesting the food-grade EVOCs emulsion and then providing additional breath samples at subsequent time points up to 90 minutes post ingestion.
Read the detailed description
The diagnosis of non-alcoholic steatohepatitis (NASH) still requires liver biopsy, an invasive procedure that can lead to complications. Impaired hepatic function, associated with chronic liver diseases, changes the metabolic pathways responsible for the biotransformation of certain volatile organic compounds (VOCs) exhaled in breath. Consequently, abundance of these VOCs on breath changes in the presence of chronic liver diseases and could be used as a non-invasive diagnostic tool. To date, identified VOCs with classification performance for chronic liver diseases are of exogenous origin and their abundance on breath is not only related to liver malfunction, but also to the extent of the everyday exposure to these compounds, mainly through dietary intake. To overcome this limitation, we established the exogenous volatile organic compound (EVOC) approach, based on the administration of a defined dose of a compound followed by its measurement on breath at different timepoints. We tested several compounds in healthy subjects and found that their levels on breath peak ~10 minutes after administration, followed by a progressive reduction. NASH-associated alterations of gene expression [1], and/or impaired hepatic function is expected to alter the reduction of administered compound on breath allowing for classification between NASH subjects and healthy controls. We plan to administer a cocktail of EVOCs made of limonene, benzyl alcohol, 2- pentanone, 2-butanol, and nonanal, compounds safe for human consumption, approved, and widely used in the European Union as food flavoring agents. The amounts we will administer are well below thresholds found to cause side effects in human or animal models. The working hypothesis is that NASH-induced changes of hepatic clearance of administered food flavors alters their amounts measured in breath allowing differentiation between NASH and healthy liver conditions. We aim to conduct a cross-sectional study with the objective to identify if changes in EVOCs metabolism have a diagnostic potential for subjects with advanced fibrosis.
Subjects with FibroScan-confirmed fibrosis are asked to fast overnight. Then they provide a baseline breath sample, followed by oral administration of the EVOCs cocktail, and sampling of additional breath samples at subsequent timepoints up to 90 minutes post ingestion
- Conditions
- Liver Fibrosis, NASH, Liver Diseases
- Being tested
- EVOCs emulsion
- Medical subject headings
- Liver Cirrhosis, Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EVOCs emulsionOther
Also called Selected-ion flow-tube mass spectrometry (SIFT-MS)
Continuous breath sampling directly into SIFT-MS equipment. The instrument is equipped with a mouthpiece connected to the SIFT inlet where the subject blows in and the breath is analyzed in real-time
| Study group | Role | What they receive |
|---|---|---|
| Early Liver Disease | A total of 30 subjects with fibroscan confirmed liver fibrosis likely due to non-alcoholic steatohepatitis (NASH) will be recruited. Receives: Other: EVOCs emulsion |
What is being measured
The primary outcome is the main question the study is designed to answer.
To demonstrate the potential of using breath profiles of administered flavoring compounds and their metabolites to assess liver fibrosis.
To determine this the breath profiles of subjects with liver fibrosis will be compared to the breath profiles from a previously measured healthy cohort.
Measured: Through study completion, an average of 4 months
Secondary outcomes (2)
To demonstrate intra-subject variability in NASH patients is comparable to that in healthy volunteers observed previously.
Measured: Through study completion, an average of 4 months
To demonstrate that there are correlations between abundance of EVOCs and/or their metabolites on breath and fibrosis stage and scoring determined by blood metrics or imaging modalities previously collected.
Measured: Through study completion, an average of 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2023
- Study start21 May 2024
- Primary completion12 Dec 2024
- Study completion12 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver FibrosisStudies of the same condition, open and under way.
- 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
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Owlstone Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- North Norfolk Primary Care Practices, Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05935488
- Sponsor's protocol ID
- OML-004
- Status last verified
- Jul 2026
- First submitted
- 16 Jun 2023
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Breath Detection of Non-alcoholic Steatohepatitis (NASH)-Induced Metabolic Alterations Using Food Flavors.
- ClinicalTrials.gov ID
- NCT05935488
- Acronym / sponsor ID
- OML-004
- Conditions
- Liver Fibrosis, NASH, Liver Diseases
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Owlstone LtdIndustry (pharma, biotech, devices)
- Collaborators
- North Norfolk Primary Care Practices, Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)
- Study start
- 21 May 2024 (actual)
- Primary completion
- 12 Dec 2024 (actual)
- Study completion
- 12 Dec 2024 (actual)
- First posted
- 7 Jul 2023 (actual)
- 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 Early Liver Disease Breath Detection Study is a cross-sectional study where subjects with advanced liver fibrosis will ingest a mixture of food-grade compounds (known as Exogenous Volatile Organic Compound or EVOCs) in the form of an emulsion and then provide multiple breath samples. These EVOCs can be measured on exhaled breath and it has been found that liver diseases can affect the way EVOCs are processed in the body. The objective is to identify if changes in the way these EVOCs are processed in the body can have the potential to diagnose early stage liver diseases for these subjects. Subjects with fibro-scan confirmed fibrosis will be recruited from Norfolk and Norwich University Hospital (NNUH) by local research staff, they will be invited to take part in the study at a dedicated clinic at OneNorwich Practises a clinic based in Norwich City Centre. They will be asked to fast overnight then provide a baseline breath sample, before ingesting the food-grade EVOCs emulsion and then providing additional breath samples at subsequent time points up to 90 minutes post ingestion.
Detailed description
The diagnosis of non-alcoholic steatohepatitis (NASH) still requires liver biopsy, an invasive procedure that can lead to complications. Impaired hepatic function, associated with chronic liver diseases, changes the metabolic pathways responsible for the biotransformation of certain volatile organic compounds (VOCs) exhaled in breath. Consequently, abundance of these VOCs on breath changes in the presence of chronic liver diseases and could be used as a non-invasive diagnostic tool. To date, identified VOCs with classification performance for chronic liver diseases are of exogenous origin and their abundance on breath is not only related to liver malfunction, but also to the extent of the everyday exposure to these compounds, mainly through dietary intake. To overcome this limitation, we established the exogenous volatile organic compound (EVOC) approach, based on the administration of a defined dose of a compound followed by its measurement on breath at different timepoints. We tested several compounds in healthy subjects and found that their levels on breath peak ~10 minutes after administration, followed by a progressive reduction. NASH-associated alterations of gene expression [1], and/or impaired hepatic function is expected to alter the reduction of administered compound on breath allowing for classification between NASH subjects and healthy controls. We plan to administer a cocktail of EVOCs made of limonene, benzyl alcohol, 2- pentanone, 2-butanol, and nonanal, compounds safe for human consumption, approved, and widely used in the European Union as food flavoring agents. The amounts we will administer are well below thresholds found to cause side effects in human or animal models. The working hypothesis is that NASH-induced changes of hepatic clearance of administered food flavors alters their amounts measured in breath allowing differentiation between NASH and healthy liver conditions. We aim to conduct a cross-sectional study with the objective to identify if changes in EVOCs metabolism have a diagnostic potential for subjects with advanced fibrosis.
Subjects with FibroScan-confirmed fibrosis are asked to fast overnight. Then they provide a baseline breath sample, followed by oral administration of the EVOCs cocktail, and sampling of additional breath samples at subsequent timepoints up to 90 minutes post ingestion
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Early Liver Disease | – | Other: EVOCs emulsionA total of 30 subjects with fibroscan confirmed liver fibrosis likely due to non-alcoholic steatohepatitis (NASH) will be recruited. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- A total of 30 subjects with fibroscan confirmed liver fibrosis likely due to NASH will be recruited. To be eligible for the study participation, subjects must meet the inclusion and exclusion criteria.
Key inclusion criteria (5 listed)
- Able to provide written informed consent.
- >18 years old.
- Body weight > 50 kg.
- Alcohol consumption - does not drink to excess (>30 g/day in men, >20 g/day in women).
- Fibroscan kilopascal (kPa) between 8.5 and 13.5 within 6 months and/or a liver biopsy within the last 3 years showing a fibrosis activity score ≥ F2 and a NAS score > 4 with a diagnosis of non alcoholic steatohepatitis (NASH)
Key exclusion criteria (9 listed)
- (Anticipated) inability to complete the breath sampling procedure due to e.g. inability to maintain adequate ventilation unaided or claustrophobia / Inability to comply with the study procedures in the opinion of the investigator.
- Participant has cirrhosis.
- Participant has current hepatocellular carcinoma (HCC) or currently being treated for HCC. Those previously with/treated for and now clear of HCC can be recruited.
- Participant's cause of liver disease is known to be one of alcohol abuse, hepatitis, autoimmune hepatitis, medications, haemochromatosis, alpha1 antitrypsin deficiency, Wilson disease, biliary problems.
- Presence of current common cold or any other infectious disease including any recent symptoms of Covid-19.
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 |
|---|---|---|
| EVOCs emulsionAlso: Selected-ion flow-tube mass spectrometry (SIFT-MS)Continuous breath sampling directly into SIFT-MS equipment. The instrument is equipped with a mouthpiece connected to the SIFT inlet where the subject blows in and the breath is analyzed in real-time | Other | Early Liver Disease |
Primary outcome
To demonstrate the potential of using breath profiles of administered flavoring compounds and their metabolites to assess liver fibrosis.
Time frame: Through study completion, an average of 4 months
To determine this the breath profiles of subjects with liver fibrosis will be compared to the breath profiles from a previously measured healthy cohort.
2 secondary outcomes
To demonstrate intra-subject variability in NASH patients is comparable to that in healthy volunteers observed previously.
Time frame: Through study completion, an average of 4 months
To demonstrate that there are correlations between abundance of EVOCs and/or their metabolites on breath and fibrosis stage and scoring determined by blood metrics or imaging modalities previously collected.
Time frame: Through study completion, an average of 4 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 9 Jul 2026.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Liver Fibrosis and NASH, run by Owlstone Ltd 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 5 inclusion and 9 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 9 Jul 2026. 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?
To demonstrate the potential of using breath profiles of administered flavoring compounds and their metabolites to assess liver fibrosis. (time frame: Through study completion, an average of 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jul 2026.