Liver DiseasePhase 1NOCTUANCT02098785
Inhibition of VAP-1 by Caffeine in Healthy Human Volunteers Study
A Phase 1 study testing Caffeine citrate in people with Liver Disease, run by University of Birmingham at 1 site in United Kingdom.
Trial summary
Worldwide, liver related morbidity and mortality continue to rise. It is the 5th commonest cause of death in the UK. Liver damage consists of two main components - a) damage to the cells of the liver, called hepatocytes, meaning the liver cannot function properly leading to jaundice (yellow appearance of the skin… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Liver Disease
- What is being tested?
- Caffeine citrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Mar 2018to Sep 2018
- Phase
- Phase 1
- 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy human volunteers aged 18-70 inclusive
- No significant medical problems (as determined by a screening questionnaire)
- Written informed consent given by the patient
Who cannot join
- Currently pregnant or breast feeding
- Psychiatric, addictive or any disorder which compromises ability to give truly informed consent for participation in this study or comply with the requirements of the study
- Other serious underlying medical conditions that could impair the ability of the patient to participate in the study
- Unable to travel for study visit
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Birmingham, UK
Birmingham, West Midlands, B15 2TT
About this study
Official title: Phase I Clinical Trial Investigating the Effects of Caffeine Citrate on Serum Vascular Adhesion Protein -1 (VAP-1) Levels in Healthy Volunteers.
Worldwide, liver related morbidity and mortality continue to rise. It is the 5th commonest cause of death in the UK. Liver damage consists of two main components - a) damage to the cells of the liver, called hepatocytes, meaning the liver cannot function properly leading to jaundice (yellow appearance of the skin and/or eyes) and liver failure and b) scarring of the liver, called Cirrhosis, leading to impaired function and inadequate blood flow through the liver with potential to develop into cancer. Manifestations of this state include ascites (fluid in the tummy) and varices (swollen blood vessels in the food pipe). Liver transplant is currently the only curative treatment for end stage chronic liver disease. Unfortunately its high demand has not been matched by an equivalent rise in liver donations and even when a transplant has occurred there are numerous lifestyle effects such as immunosuppression and kidney impairment thus outcome remains poor for many patients. Coffee has been shown to have mortality benefit in humans and drinking two to three cups a day was associated with a 40% reduced risk of developing cirrhosis, particularly alcohol related; and higher the more cups consumed. Previous work has demonstrated coffee reduces the level of fibrosis in the liver by interrupting signalling pathways, blocking the effects of special products, called cytokines, and reducing accumulation of iron. The investigators' hypothesis is that given the potential for caffeine to be used as a treatment in SSAO activity associated diseases it is important to see if the activity of SSAO can be blocked in healthy humans too. The Investigators' aim to examine the effect of caffeine on circulating VAP-1 levels in large numbers of healthy volunteers to assess its potential as an attractive therapeutic target in view of its low toxicity and widespread availability.
Read the detailed description
One such enzyme known as VAP-1 (vascular adhesion protein-1) is expressed at high levels in liver endothelial cells and studies involving blockage of VAP-1 activity have demonstrated it is involved in a reaction where break down products such as hydrogen peroxide and ammonia active signalling pathways to assist in the movement of cells from blood vessels to the liver. VAP-1 levels become elevated during chronic inflammation in blood vessels of the gut, tonsils, skin and synovium albeit most selectively in liver. Recently, circulating VAP-1 has been demonstrated to be elevated in certain liver diseases particularly alcoholic liver disease. Initial animal studies have shown that activity of the enzyme SSAO (Semicarbazide-sensitive amine oxidase) can be effectively blocked by caffeine administration and that caffeine also blocks the activity of fat cells, known as adipose cells, thus protective against obesity too. SSAO arises from the same family of enzymes as VAP-1 thus importantly shares transferable properties. This information led to small, experimental studies in human liver that corroborate these findings but did not show how caffeine was affecting VAP-1 in the blood.
- Conditions
- Liver Disease
- Being tested
- Caffeine citrate
- Keywords
- VAP, liver, hepatology, caffeine
- Medical subject headings
- Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Caffeine citrateDrug
Also called Peyona
Oral solution
| Study group | Role | What they receive |
|---|---|---|
| Caffeine citrate (Peyona) 400mg | Experimental | Caffeine Citrate (Peyona) 400mg single dose (20ml oral solution) Receives: Drug: Caffeine citrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
VAP-1 serum levels
The aim of the trial is to examine whether caffeine blocks vascular adhesion protein-1 (VAP-1) activity in the blood of healthy human volunteers and thus prove to be of medicinal value in liver disease.
Measured: VAP-1 serum levels at 60, 90 and 120 minutes post administration of caffeine citrate (Peyona)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2014 (estimated)
- Study startMar 2018 (estimated)
- Primary completionSep 2018 (estimated)
- Study completionSep 2018 (estimated)
Why it stopped: Local resource issue - never actually started post ethics approval.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver DiseaseStudies 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Adams, MD, Principal investigator, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02098785
- Sponsor's protocol ID
- RG_14-045
- Acronym
- NOCTUA
- Status last verified
- May 2017
- First submitted
- 25 Mar 2014
- Last updated
- 19 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial Investigating the Effects of Caffeine Citrate on Serum Vascular Adhesion Protein -1 (VAP-1) Levels in Healthy Volunteers.
- ClinicalTrials.gov ID
- NCT02098785
- Acronym / sponsor ID
- NOCTUA / RG_14-045
- Conditions
- Liver Disease
- Keywords
- VAP, liver, hepatology, caffeine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Local resource issue - never actually started post ethics approval.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Study start
- Mar 2018 (estimated)
- Primary completion
- Sep 2018 (estimated)
- Study completion
- Sep 2018 (estimated)
- First posted
- 28 Mar 2014 (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.
Worldwide, liver related morbidity and mortality continue to rise. It is the 5th commonest cause of death in the UK. Liver damage consists of two main components - a) damage to the cells of the liver, called hepatocytes, meaning the liver cannot function properly leading to jaundice (yellow appearance of the skin and/or eyes) and liver failure and b) scarring of the liver, called Cirrhosis, leading to impaired function and inadequate blood flow through the liver with potential to develop into cancer. Manifestations of this state include ascites (fluid in the tummy) and varices (swollen blood vessels in the food pipe). Liver transplant is currently the only curative treatment for end stage chronic liver disease. Unfortunately its high demand has not been matched by an equivalent rise in liver donations and even when a transplant has occurred there are numerous lifestyle effects such as immunosuppression and kidney impairment thus outcome remains poor for many patients. Coffee has been shown to have mortality benefit in humans and drinking two to three cups a day was associated with a 40% reduced risk of developing cirrhosis, particularly alcohol related; and higher the more cups consumed. Previous work has demonstrated coffee reduces the level of fibrosis in the liver by interrupting signalling pathways, blocking the effects of special products, called cytokines, and reducing accumulation of iron. The investigators' hypothesis is that given the potential for caffeine to be used as a treatment in SSAO activity associated diseases it is important to see if the activity of SSAO can be blocked in healthy humans too. The Investigators' aim to examine the effect of caffeine on circulating VAP-1 levels in large numbers of healthy volunteers to assess its potential as an attractive therapeutic target in view of its low toxicity and widespread availability.
Detailed description
One such enzyme known as VAP-1 (vascular adhesion protein-1) is expressed at high levels in liver endothelial cells and studies involving blockage of VAP-1 activity have demonstrated it is involved in a reaction where break down products such as hydrogen peroxide and ammonia active signalling pathways to assist in the movement of cells from blood vessels to the liver. VAP-1 levels become elevated during chronic inflammation in blood vessels of the gut, tonsils, skin and synovium albeit most selectively in liver. Recently, circulating VAP-1 has been demonstrated to be elevated in certain liver diseases particularly alcoholic liver disease. Initial animal studies have shown that activity of the enzyme SSAO (Semicarbazide-sensitive amine oxidase) can be effectively blocked by caffeine administration and that caffeine also blocks the activity of fat cells, known as adipose cells, thus protective against obesity too. SSAO arises from the same family of enzymes as VAP-1 thus importantly shares transferable properties. This information led to small, experimental studies in human liver that corroborate these findings but did not show how caffeine was affecting VAP-1 in the blood.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Caffeine citrate (Peyona) 400mg | Experimental | Drug: Caffeine citrateCaffeine Citrate (Peyona) 400mg single dose (20ml oral solution) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Healthy human volunteers aged 18-70 inclusive
- No significant medical problems (as determined by a screening questionnaire)
- Written informed consent given by the patient
Key exclusion criteria (4 listed)
- Currently pregnant or breast feeding
- Psychiatric, addictive or any disorder which compromises ability to give truly informed consent for participation in this study or comply with the requirements of the study
- Other serious underlying medical conditions that could impair the ability of the patient to participate in the study
- Unable to travel for study visit
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 |
|---|---|---|
| Caffeine citrateAlso: PeyonaOral solution | Drug | Caffeine citrate (Peyona) 400mg |
Primary outcome
VAP-1 serum levels
Time frame: VAP-1 serum levels at 60, 90 and 120 minutes post administration of caffeine citrate (Peyona)
The aim of the trial is to examine whether caffeine blocks vascular adhesion protein-1 (VAP-1) activity in the blood of healthy human volunteers and thus prove to be of medicinal value in liver disease.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2018.
- Individual participant dataSharing planned: Undecided
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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.
David Adams, MD principal investigator
University of Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Caffeine citrate in people with Liver Disease, run by University of Birmingham 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 4 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: withdrawn, as of the sponsor's last update on 19 Apr 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
VAP-1 serum levels (time frame: VAP-1 serum levels at 60, 90 and 120 minutes post administration of caffeine citrate (Peyona)). 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 19 Apr 2018.