Inflammatory Bowel DiseasesPSC-VancNCT05376228
A Systems Biology Approach for Identification of Host and Microbial Mechanisms and Druggable Targets for the Treatment of PSC-IBD
An observational study of Inflammatory Bowel Diseases and Primary Sclerosing Cholangitis, run by University Hospital Birmingham NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). Although rare, PSC is associated with significant and disproportionate unmet needs; with heightened risks of colorectal cancer and colectomy, and greater all-cause mortality rates compared to matched… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Inflammatory Bowel Diseases, Primary Sclerosing Cholangitis
- What is being tested?
- Oral Vancomycin
- Type of treatment
- Pill or oral medicine
- How many people
- 15 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Feb 2022to 1 Apr 2023
- 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: 15 patients with active PSC-IBD will undergo 4 weeks of treatment with open label (standard of care) oral vancomycin.
Who may be able to join
- Patients with confirmed diagnosis of primary sclerosing cholangitis and concurrent colitis
- Mild to moderately active colitis based on partial Mayo score of ≥3 and ≤6
- Scheduled for a standard of care lower GI endoscopy as part of disease assessment / surveillance
Who cannot join
- History of previous colectomy
- Isolated small bowel disease
- Stricturing , fistulating or perianal phenotype
- Use of antibiotics and/or probiotics in the prior 3 months
- Use of steroids in last 2 weeks
- Commenced thiopurines / methotrexate in last 3 months
Show all 9Show fewer
- History of intolerance to oral vancomycin
- Decompensated liver disease (Child C cirrhosis)
- Active infectious diarrhoea
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
University Hospitals Birmingham NHS Foundation Trust
Birmingham, B15 2GW
Nabil Quraishi, 01213712000, nabil.quraishi@nhs.net
Nabil Quraishi
About this study
Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). Although rare, PSC is associated with significant and disproportionate unmet needs; with heightened risks of colorectal cancer and colectomy, and greater all-cause mortality rates compared to matched IBD patients. Unfortunately, no medical therapy has been proven to slow disease progression in PSC-IBD, and liver transplantation is the only lifesaving intervention for patients.
The strong association between PSC and IBD has led to several pathogenic hypotheses, in which dysregulated mucosal immune responses are proposed to contribute. Of note, the investigators recently identified distinct mucosal transcriptomic profiles in PSC-IBD; with regards bile acid metabolism, bile acid signalling, and a central role of enteric dysbiosis. In parallel, pilot data from other groups have shown that treatment with oral vancomycin (a non-absorbable, gut-specific antibiotic) attenuates colonic inflammation and improves biochemical markers of cholestasis in PSC. However, there is no mechanistic data exploring the host-microbial alterations under vancomycin treatment in PSC-IBD, neither the impact of vancomycin on bile acid circulation. The investigators of this study hypothesize that oral vancomycin attenuates colonic mucosal inflammation in PSC-IBD, by restoring gut microbiota mediated bile acid homeostatic pathways. Through these means the study aims to identify druggable gut microbial and host molecular pathways associated with bile acid mediated colonic mucosal inflammation in PSC-IBD.
Read the detailed description
Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). Although rare, PSC is associated with significant and disproportionate unmet needs; with heightened risks of colorectal cancer and colectomy, and greater all-cause mortality rates compared to age- and sex-matched IBD controls. Unfortunately, no medical therapy has been proven to slow disease progression in PSC-IBD, and liver transplantation is the only lifesaving intervention for patients. The strong association between PSC and IBD has led to several pathogenic hypotheses, in which dysregulated mucosal immune responses are proposed to contribute. Of note, the investigators of this study recently identified distinct mucosal transcriptomic profiles in PSC-IBD; with regards bile acid metabolism, bile acid signalling, and a central role of enteric dysbiosis. In parallel, pilot data from other groups have shown that treatment with oral vancomycin (a non-absorbable, gut-specific antibiotic) attenuates colonic inflammation and improves biochemical markers of cholestasis in PSC. However, there is no mechanistic data exploring the host-microbial alterations under vancomycin treatment in PSC-IBD, neither the impact of vancomycin on bile acid circulation.
In this study, fifteen PSC-IBD patients will be recruited through a large tertiary referral centre, who are undergoing lower gastrointestinal examination as per routine standard of care. Participants will be offered 4 weeks of treatment with oral vancomycin, and stool samples collected at different timepoints to evaluate changes in metagenomic, metatranscriptomic, and bile acid profiles. Colonic biopsies will be collected at baseline and at week 4 (flexible sigmoidoscopy) and subjected to FACS sorted RNA sequencing to identify changes in colonic epithelial cell pathways. Multi-omics data integration will be performed to uncover combinations of predictive profiles, model microbial networks, and host transcriptomic changes implicated in the response to oral vancomycin. This study will inform the downstream identification of specific host molecular and microbial pathways that has a potential for development of therapeutic targets for PSC-IBD in clinical practice.
- Being tested
- Oral Vancomycin
- Keywords
- primary sclerosing cholangitis, inflammatory bowel disease, microbiome, vancomycin
- Medical subject headings
- Inflammatory Bowel Diseases, Cholangitis, Sclerosing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral VancomycinDrug
As part of standard of care
What is being measured
The primary outcome is the main question the study is designed to answer.
Identify stool metagenomic, metatranscriptomic and bile acid profiles following treatment with oral vancomycin in PSC-IBD
Measured: 12 months
Investigate changes in colonic mucosal epithelial bile acid and immunological pathways through FACS sorted RNA-sequencing following oral vancomycin
Measured: 12 months
Identification of druggable host molecular and microbial targets through multi-omic integration analysis
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 posted17 May 2022
- Study start1 Feb 2022
- Primary completion1 Feb 2023 (estimated)
- Study completion1 Apr 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Inflammatory Bowel DiseasesStudies 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
- Prospective
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Birmingham NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohammed Nabil Quraishi, University Hospital Birmingham NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05376228
- Sponsor's protocol ID
- RRK7338
- Acronym
- PSC-Vanc
- Status last verified
- May 2022
- First submitted
- 11 May 2022
- Last updated
- 1 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Quraishi MN, Acharjee A, Beggs AD, Horniblow R, Tselepis C, Gkoutos G, Ghosh S, Rossiter AE, Loman N, van Schaik W, Withers D, Walters JRF, Hirschfield GM, Iqbal TH. A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways. J Crohns Colitis. 2020 Jul 30;14(7):935-947. doi: 10.1093/ecco-jcc/jjaa021.
PubMed 32016358Quraishi MN, Cheesbrough J, Rimmer P, Mullish BH, Sharma N, Efstathiou E, Acharjee A, Gkoutus G, Patel A, Marchesi JR, Camuzeaux S, Chappell K, Valdivia-Garcia MA, Ferguson J, Brookes MJ, Walmsley M, Rossiter AE, van Schaik W, McInnes RS, Cooney R, Trauner M, Beggs AD, Iqbal TH, Trivedi PJ. Open Label Vancomycin in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Improved Colonic Disease Activity and Associations With Changes in Host-Microbiome-Metabolomic Signatures. J Crohns Colitis. 2025 Feb 4;19(2):jjae189. doi: 10.1093/ecco-jcc/jjae189.
PubMed 39673746
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Systems Biology Approach for Identification of Host and Microbial Mechanisms and Druggable Targets for the Treatment of PSC-IBD
- ClinicalTrials.gov ID
- NCT05376228
- Acronym / sponsor ID
- PSC-Vanc / RRK7338
- Keywords
- primary sclerosing cholangitis, inflammatory bowel disease, microbiome, vancomycin
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- University Hospital Birmingham NHS Foundation TrustUniversity, hospital or other
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 1 Feb 2023 (estimated)
- Study completion
- 1 Apr 2023 (estimated)
- First posted
- 17 May 2022 (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.
Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). Although rare, PSC is associated with significant and disproportionate unmet needs; with heightened risks of colorectal cancer and colectomy, and greater all-cause mortality rates compared to matched IBD patients. Unfortunately, no medical therapy has been proven to slow disease progression in PSC-IBD, and liver transplantation is the only lifesaving intervention for patients.
The strong association between PSC and IBD has led to several pathogenic hypotheses, in which dysregulated mucosal immune responses are proposed to contribute. Of note, the investigators recently identified distinct mucosal transcriptomic profiles in PSC-IBD; with regards bile acid metabolism, bile acid signalling, and a central role of enteric dysbiosis. In parallel, pilot data from other groups have shown that treatment with oral vancomycin (a non-absorbable, gut-specific antibiotic) attenuates colonic inflammation and improves biochemical markers of cholestasis in PSC. However, there is no mechanistic data exploring the host-microbial alterations under vancomycin treatment in PSC-IBD, neither the impact of vancomycin on bile acid circulation. The investigators of this study hypothesize that oral vancomycin attenuates colonic mucosal inflammation in PSC-IBD, by restoring gut microbiota mediated bile acid homeostatic pathways. Through these means the study aims to identify druggable gut microbial and host molecular pathways associated with bile acid mediated colonic mucosal inflammation in PSC-IBD.
Detailed description
Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). Although rare, PSC is associated with significant and disproportionate unmet needs; with heightened risks of colorectal cancer and colectomy, and greater all-cause mortality rates compared to age- and sex-matched IBD controls. Unfortunately, no medical therapy has been proven to slow disease progression in PSC-IBD, and liver transplantation is the only lifesaving intervention for patients. The strong association between PSC and IBD has led to several pathogenic hypotheses, in which dysregulated mucosal immune responses are proposed to contribute. Of note, the investigators of this study recently identified distinct mucosal transcriptomic profiles in PSC-IBD; with regards bile acid metabolism, bile acid signalling, and a central role of enteric dysbiosis. In parallel, pilot data from other groups have shown that treatment with oral vancomycin (a non-absorbable, gut-specific antibiotic) attenuates colonic inflammation and improves biochemical markers of cholestasis in PSC. However, there is no mechanistic data exploring the host-microbial alterations under vancomycin treatment in PSC-IBD, neither the impact of vancomycin on bile acid circulation.
In this study, fifteen PSC-IBD patients will be recruited through a large tertiary referral centre, who are undergoing lower gastrointestinal examination as per routine standard of care. Participants will be offered 4 weeks of treatment with oral vancomycin, and stool samples collected at different timepoints to evaluate changes in metagenomic, metatranscriptomic, and bile acid profiles. Colonic biopsies will be collected at baseline and at week 4 (flexible sigmoidoscopy) and subjected to FACS sorted RNA sequencing to identify changes in colonic epithelial cell pathways. Multi-omics data integration will be performed to uncover combinations of predictive profiles, model microbial networks, and host transcriptomic changes implicated in the response to oral vancomycin. This study will inform the downstream identification of specific host molecular and microbial pathways that has a potential for development of therapeutic targets for PSC-IBD in clinical practice.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 15 patients with active PSC-IBD will undergo 4 weeks of treatment with open label (standard of care) oral vancomycin.
Key inclusion criteria (3 listed)
- Patients with confirmed diagnosis of primary sclerosing cholangitis and concurrent colitis
- Mild to moderately active colitis based on partial Mayo score of ≥3 and ≤6
- Scheduled for a standard of care lower GI endoscopy as part of disease assessment / surveillance
Key exclusion criteria (9 listed)
- History of previous colectomy
- Isolated small bowel disease
- Stricturing , fistulating or perianal phenotype
- Use of antibiotics and/or probiotics in the prior 3 months
- Use of steroids in last 2 weeks
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 |
|---|---|---|
| Oral VancomycinAs part of standard of care | Drug | – |
Primary outcome
Identify stool metagenomic, metatranscriptomic and bile acid profiles following treatment with oral vancomycin in PSC-IBD
Time frame: 12 months
Investigate changes in colonic mucosal epithelial bile acid and immunological pathways through FACS sorted RNA-sequencing following oral vancomycin
Time frame: 12 months
Identification of druggable host molecular and microbial targets through multi-omic integration analysis
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2022.
- Background: PubMed 32016358Quraishi MN, Acharjee A, Beggs AD, Horniblow R, Tselepis C, Gkoutos G, Ghosh S, Rossiter AE, Loman N, van Schaik W, Withers D, Walters JRF, Hirschfield GM, Iqbal TH. A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways. J Crohns Colitis. 2020 Jul 30;14(7):935-947. doi: 10.1093/ecco-jcc/jjaa021.
- Derived from this study: PubMed 39673746Quraishi MN, Cheesbrough J, Rimmer P, Mullish BH, Sharma N, Efstathiou E, Acharjee A, Gkoutus G, Patel A, Marchesi JR, Camuzeaux S, Chappell K, Valdivia-Garcia MA, Ferguson J, Brookes MJ, Walmsley M, Rossiter AE, van Schaik W, McInnes RS, Cooney R, Trauner M, Beggs AD, Iqbal TH, Trivedi PJ. Open Label Vancomycin in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Improved Colonic Disease Activity and Associations With Changes in Host-Microbiome-Metabolomic Signatures. J Crohns Colitis. 2025 Feb 4;19(2):jjae189. doi: 10.1093/ecco-jcc/jjae189.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- 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.
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 Inflammatory Bowel Diseases and Primary Sclerosing Cholangitis, run by University Hospital Birmingham NHS Foundation Trust 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 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: status not confirmed, as of the sponsor's last update on 1 Jun 2022. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nabil Quraishi, PhD, MRCP (01213712000, nabil.quraishi@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identify stool metagenomic, metatranscriptomic and bile acid profiles following treatment with oral vancomycin in PSC-IBD (time frame: 12 months). The study lists 3 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 NCT05376228, which also lists 2 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 1 Jun 2022.