Crohn DiseaseNCT06073288
Unveiling the Microbial Impact on Intestinal Fibrosis
An observational study of Crohn Disease, run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
Crohn's disease (CD), belonging to the class of Inflammatory Bowel Diseases, is a chronic inflammatory disorder that may affect any location of the gastrointestinal tract. It is characterized by transmural inflammation and an overwhelming immune response of the gut mucosa, which leads to severe clinical symptoms. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Crohn Disease
- What is being tested?
- Surgical specimens of CD and no-IBD patients
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 1 Nov 2023to 1 Nov 2026
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 20 patients undergoing surgery: - 15 CD patients (5 patients/stage: (B1 (more inflammatory, non-structuring), B2 (structuring, non-penetrating) and B3 (structuring and penetrating). Patient stratification is based on previous classifications done in accordance with the standard of care through TC, RMI or Ecography. For this reason, patients classification is known before surgery. - 5 patients without IBD-related diseases (ex. diverticulitis)
Who may be able to join
- Adult patients ≥18 and <70 years
- All patients will sign the informed consent
- Given that it is an observational study, also pregnant and breastfeed patients could be included
- Additionally, for CD patients:
- classification on different stages: (B1 (more inflammatory, non-structuring), B2 (structuring, non-penetrating) and B3 (structuring and penetrating). Patient stratification is based on previous classifications done in accordance with the standard of care through TC, RMI or Ecography.
- Additionally, for non-IBD patients:
- subjects undergoing surgery for non-IBD diseases (ex. diverticulitis) in accordance with the standard of care
Who cannot join
- For CD patients:
- CD subjects without previously classification in B1, B2, B3
- Patients <18 years or > 70 years
- Patients without the signed informed consent
- For non-IBD patients:
- Patients <18 years or > 70 years
- Patients without the signed informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Unveiling the Microbial Impact on Intestinal Fibrosis: New Insights for the Pathogenesis and Treatment of Crohn's Disease-associated Complications
Crohn's disease (CD), belonging to the class of Inflammatory Bowel Diseases, is a chronic inflammatory disorder that may affect any location of the gastrointestinal tract. It is characterized by transmural inflammation and an overwhelming immune response of the gut mucosa, which leads to severe clinical symptoms. More than 50% of CD patients develop a penetrating or stricturing disease due to fibrostenosis, which most of the time requires surgical intervention since no therapies have been found as effective yet. Among the histological features of stricturing CD, the thickening of the muscularis mucosae and muscularis propria is the main hallmark, primarily due to the excessive proliferation of mesenchymal cells and the increased accumulation of a collagen-rich extracellular matrix in the submucosa, caused by multiple mechanisms, including i) the proliferation of existing local fibroblasts, the induction of both ii) epithelial-to-, and iii) endothelial-to-mesenchymal transition. Even if the alteration of these mucosal functions is mainly caused by the continuous tissue injury occurring during CD-associated chronic inflammation, recent reports suggested that CD associated fibrosis may be driven by inflammation-independent triggers, such as microbiota dysbiosis.
Shedding the light on this aspect of CD fibrosis may lead to the development of innovative therapeutic strategies eventually blocking the gut thickening.
Read the detailed description
This is a cross-sectional observational study involving patients with Crohn's Disease (CD) (n=15) and patients with non-Intestinal Bowel Disease (IBD) (n=5) undergoing surgery in the Gastroenterology and Digestive Endoscopy unit within Gastro Center (IRCCS Ospedale San Raffaele) according to the standard of care.
Specimens will be collected during the surgery, without other risks for the patients, since we will use only material left after pathologist analysis.
CD-derived surgical specimens will be processed to obtain a cell suspension, that will be frozen and stored for the following cell sorting. For non-IBD tissue processing, each surgical specimen will be cut into two pieces. One will be processed to obtain the cell suspension to be stored, whereas the remaining tissue will be processed to isolate lamina propria fibroblasts and endothelial cells, as well as to generate epithelial organoids.
Ospedale San Raffaele (OSR - Operative Unit (UO)1 (UO1)) is the promoter of this study. The other center participating in the study is University of Milan (UO2), which has in charge the development of 3D microfluidic devices for the in vitro experiments. Patients will be enrolled only in UO1.
- Conditions
- Crohn Disease
- Being tested
- Surgical specimens of CD and no-IBD patients
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surgical specimens of CD and no-IBD patientsOther
Specimens of CD patients and patients without IBD-related disease (ex. diverticulitis) will be collected during the surgery, without other risks for the patients, since we will use only material left after pathologist analysis
| Study group | Role | What they receive |
|---|---|---|
| Crohn's Disease (CD) | 15 CD patients (5 patients/stage: (B1 (more inflammatory, non-structuring), B2 (structuring, non-penetrating) and B3 (structuring and penetrating).
Patient stratification is based on previous classifications done in accordance with the standard of care through TC, RMI or Ecography. For this reason, patients classification is known before surgery. Receives: Other: Surgical specimens of CD and no-IBD patients | |
| non-Intestinal Bowel Disease patients (no-IBD) | 5 patients without IBD-related diseases (ex. diverticulitis) Receives: Other: Surgical specimens of CD and no-IBD patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
To perform flow cytometry, RNAseq, metatranscriptomics, transcriptomics and lipidomics on CD and non-IBD cells
To evaluate how bacterial factors may impact the transcriptomic state of the different host cell compartments in terms of profibrotic pathway and gene activation. Cells will undergo FACS for CD31, EpCam, and CD90 markers for isolating endothelial cells, epithelial cells, and fibroblasts, respectively, as the well-known cellular players in the fibrotic process. Single-cell populations will undergo library preparation and will be analyzed by ribo-minus RNAseq at 30M reads of depth. Metatranscriptomics for profiling the microbial composition, as well as the transcriptomics to determine both the differential gene expression (DGE) and the Gene Set Enrichment Analysis (GSEA) will be performed. The relative abundances of Brevibacteriaceae, Caulobacteraceae, and Sphingomonadaceae-derived factors will be calculated using Kraken2 to identify which cell subtype(s) among CD-derived fibroblasts, endothelial cells, and epithelial organoids harbor(s) the fibrotic-specific microbial composition.
Measured: 1-36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2023
- Study start1 Nov 2023 (estimated)
- Primary completion1 Oct 2024 (estimated)
- Study completion1 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe 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
- Cross-sectional
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Silvio Danese, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06073288
- Sponsor's protocol ID
- RF-2021-12372637
- Status last verified
- Oct 2023
- First submitted
- 25 Sep 2023
- Last updated
- 10 Oct 2023
- Results posted
- 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 10 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unveiling the Microbial Impact on Intestinal Fibrosis: New Insights for the Pathogenesis and Treatment of Crohn's Disease-associated Complications
- ClinicalTrials.gov ID
- NCT06073288
- Acronym / sponsor ID
- RF-2021-12372637
- Conditions
- Crohn Disease
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- 1 Nov 2023 (estimated)
- Primary completion
- 1 Oct 2024 (estimated)
- Study completion
- 1 Nov 2026 (estimated)
- First posted
- 10 Oct 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.
Crohn's disease (CD), belonging to the class of Inflammatory Bowel Diseases, is a chronic inflammatory disorder that may affect any location of the gastrointestinal tract. It is characterized by transmural inflammation and an overwhelming immune response of the gut mucosa, which leads to severe clinical symptoms. More than 50% of CD patients develop a penetrating or stricturing disease due to fibrostenosis, which most of the time requires surgical intervention since no therapies have been found as effective yet. Among the histological features of stricturing CD, the thickening of the muscularis mucosae and muscularis propria is the main hallmark, primarily due to the excessive proliferation of mesenchymal cells and the increased accumulation of a collagen-rich extracellular matrix in the submucosa, caused by multiple mechanisms, including i) the proliferation of existing local fibroblasts, the induction of both ii) epithelial-to-, and iii) endothelial-to-mesenchymal transition. Even if the alteration of these mucosal functions is mainly caused by the continuous tissue injury occurring during CD-associated chronic inflammation, recent reports suggested that CD associated fibrosis may be driven by inflammation-independent triggers, such as microbiota dysbiosis.
Shedding the light on this aspect of CD fibrosis may lead to the development of innovative therapeutic strategies eventually blocking the gut thickening.
Detailed description
This is a cross-sectional observational study involving patients with Crohn's Disease (CD) (n=15) and patients with non-Intestinal Bowel Disease (IBD) (n=5) undergoing surgery in the Gastroenterology and Digestive Endoscopy unit within Gastro Center (IRCCS Ospedale San Raffaele) according to the standard of care.
Specimens will be collected during the surgery, without other risks for the patients, since we will use only material left after pathologist analysis.
CD-derived surgical specimens will be processed to obtain a cell suspension, that will be frozen and stored for the following cell sorting. For non-IBD tissue processing, each surgical specimen will be cut into two pieces. One will be processed to obtain the cell suspension to be stored, whereas the remaining tissue will be processed to isolate lamina propria fibroblasts and endothelial cells, as well as to generate epithelial organoids.
Ospedale San Raffaele (OSR - Operative Unit (UO)1 (UO1)) is the promoter of this study. The other center participating in the study is University of Milan (UO2), which has in charge the development of 3D microfluidic devices for the in vitro experiments. Patients will be enrolled only in UO1.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Crohn's Disease (CD) | – | Other: Surgical specimens of CD and no-IBD patients15 CD patients (5 patients/stage: (B1 (more inflammatory, non-structuring), B2 (structuring, non-penetrating) and B3 (structuring and penetrating). Patient stratification is based on previous classifications done in accordance with the standard of care through TC, RMI or Ecography. For this reason, patients classification is known before surgery. |
| non-Intestinal Bowel Disease patients (no-IBD) | – | Other: Surgical specimens of CD and no-IBD patients5 patients without IBD-related diseases (ex. diverticulitis) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 20 patients undergoing surgery: - 15 CD patients (5 patients/stage: (B1 (more inflammatory, non-structuring), B2 (structuring, non-penetrating) and B3 (structuring and penetrating). Patient stratification is based on previous classifications done in accordance with the standard of care through TC, RMI or Ecography. For this reason, patients classification is known before surgery. - 5 patients without IBD-related diseases (ex. diverticulitis)
Key inclusion criteria (7 listed)
- Adult patients ≥18 and <70 years
- All patients will sign the informed consent
- Given that it is an observational study, also pregnant and breastfeed patients could be included
- classification on different stages: (B1 (more inflammatory, non-structuring), B2 (structuring, non-penetrating) and B3 (structuring and penetrating). Patient stratification is based on previous classifications done in accordance with the standard of care through TC, RMI or Ecography.
- subjects undergoing surgery for non-IBD diseases (ex. diverticulitis) in accordance with the standard of care
Key exclusion criteria (7 listed)
- CD subjects without previously classification in B1, B2, B3
- Patients <18 years or > 70 years
- Patients without the signed informed consent
- Patients <18 years or > 70 years
- Patients without the signed informed consent
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 |
|---|---|---|
| Surgical specimens of CD and no-IBD patientsSpecimens of CD patients and patients without IBD-related disease (ex. diverticulitis) will be collected during the surgery, without other risks for the patients, since we will use only material left after pathologist analysis | Other | Crohn's Disease (CD), non-Intestinal Bowel Disease patients (no-IBD) |
Primary outcome
To perform flow cytometry, RNAseq, metatranscriptomics, transcriptomics and lipidomics on CD and non-IBD cells
Time frame: 1-36 months
To evaluate how bacterial factors may impact the transcriptomic state of the different host cell compartments in terms of profibrotic pathway and gene activation. Cells will undergo FACS for CD31, EpCam, and CD90 markers for isolating endothelial cells, epithelial cells, and fibroblasts, respectively, as the well-known cellular players in the fibrotic process. Single-cell populations will undergo library preparation and will be analyzed by ribo-minus RNAseq at 30M reads of depth. Metatranscriptomics for profiling the microbial composition, as well as the transcriptomics to determine both the differential gene expression (DGE) and the Gene Set Enrichment Analysis (GSEA) will be performed. The relative abundances of Brevibacteriaceae, Caulobacteraceae, and Sphingomonadaceae-derived factors will be calculated using Kraken2 to identify which cell subtype(s) among CD-derived fibroblasts, endothelial cells, and epithelial organoids harbor(s) the fibrotic-specific microbial composition.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2023.
- 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 Crohn Disease, run by IRCCS San Raffaele at 1 site in Italy.
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 7 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: status not confirmed, as of the sponsor's last update on 10 Oct 2023. 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 Italy. 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 Federica Ungaro (0226437864, ungaro-federica@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To perform flow cytometry, RNAseq, metatranscriptomics, transcriptomics and lipidomics on CD and non-IBD cells (time frame: 1-36 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 10 Oct 2023.