- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05935488
Early Liver Disease Breath Detection
Breath Detection of Non-alcoholic Steatohepatitis (NASH)-Induced Metabolic Alterations Using Food Flavors.
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Louise Nicholson-Scott
- Phone Number: 01223428200
- Email: NNN@owlstone.co.uk
Study Locations
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Norfolk
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Norwich, Norfolk, United Kingdom, NR11RB
- One Norwich Practises
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Contact:
- Clare Reynolds
- Email: clare.reynolds10@nhs.net
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Principal Investigator:
- Serge Engamba
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- 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)
Exclusion Criteria:
- (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.
- 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.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Early Liver Disease
A total of 30 subjects with fibroscan confirmed liver fibrosis likely due to non-alcoholic steatohepatitis (NASH) will be recruited.
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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 Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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To determine this the breath profiles of subjects with liver fibrosis will be compared to the breath profiles from a previously measured healthy cohort.
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Through study completion, an average of 4 months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
Through study completion, an average of 4 months
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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
|
Through study completion, an average of 4 months
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- OML-004
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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