Crohn Disease (CD)NCT06720961
The Microbial Impact on Intestinal Fibrosis and the Associated Immune Microenvironment in Crohn's Disease
An observational study of Crohn Disease (CD), run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
The goal of this study is to find out if there is a direct connection between an imbalance of gut bacteria and the development of scar tissue in the gut by identifying important bacterial proteins found in scarred gut tissue. Read more about this study
- Who is it for?
- Ages 18 to 69 yearsHealthy volunteers can take part
- Conditions the study is for
- Crohn Disease (CD)
- What is being tested?
- Collection of surgical specimen and Collection of stool sample
- Type of treatment
- Surgery or procedure
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- Apr 2025to Jan 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 69 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: We will enroll 15 CD patients and 5 patients without IBD-related diseases (ex. diverticulitis) undergoing surgery according to the normal clinical practice for a total of 20 patients as following: - 15 patients with CD (5 patients/stage: B1 (more inflammatory, non-structuring), B2 (structuring, non-penetrating) and B3 (structuring and penetrating). Patients will be stratified according to CT, MRI or ultrasound analysis (stratification already known before surgery) - 5 patients without IBD-related diseases (e.g. diverticulitis) All patients will be recruited only from San Raffaele Hospital (OSR). The participation is voluntary and the patient is allowed to refuse further participation in the protocol whenever he/she wants. Participation in the study will not change the diagnostic-therapeutic treatment that patients undergo following the clinical practice, since patients will continue to be treated in accordance with clinical practice regardless of the results of this study.
Who may be able to join
- Adult patients ≥18 and <70 years
- Patients able to autonomously sign the informed consent
- Non pregnant or breastfeeding patients
- For CD patients: CD patients with established diagnosis and additionally classified according to 3 stages: B1 (more inflammatory, non-stricturing), B2 (stricturing, non-penetrating) and B3 (stricturing and penetrating). Patients will be stratified on the basis of CT, MRI or ultrasound analysis (stratification already known before surgery)
- For non-IBD patients: patients with other pathologies but not affected by IBD according to the previously reported clinical and endoscopic evaluation criteria (ex. diverticulitis)
Who cannot join
- Patients <18 years or > 70 years
- Pregnant or breastfeeding patients
- For CD Patients: Subjects with CD who do not meet evaluation criteria described above
- For non-IBD patients: Patients undergoing anti-inflammatory and/or immunosuppressive treatments for IBD-related diseases
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
IRCCS San Raffaele
Milan, Italy, 20132
Federica Ungaro, PhD., +39 0226437864, ungaro.federica@hsr.it
Francesco Fiorio, +39 0226437159, fiorio.francesco@hsr.it
About this study
Official title: Unveiling the Microbial Impact on Intestinal Fibrosis and the Associated Immune Microenvironment: New Insights for the Pathogenesis and Treatment of Crohn's Disease-associated Complications
The goal of this study is to find out if there is a direct connection between an imbalance of gut bacteria and the development of scar tissue in the gut by identifying important bacterial proteins found in scarred gut tissue. Our aim is to identify which types of cells and biological processes are affected by these bacterial proteins in people with Crohn's Disease. We will also study how these bacterial proteins cause changes in 3D models of gut fibrosis.
Read the detailed description
More than 50% of CD patients develop a penetrating disease or stenosis due to fibrostenosis, which in most cases requires surgery, as no effective therapies have yet been found. The disease leads to both structural and functional alterations of the intestinal mucosa. Although the functional alteration of the mucosa is mainly caused by the continuous tissue damage that occurs during the chronic inflammation associated with CD, recent studies have suggested that the fibrosis associated with CD may be driven by triggering factors independent of inflammation, such as dysbiosis of the microbiota. Our proposal aims to establish the causal link between gut dysbiosis and fibrosis by studying the role of key bacterial proteins present in fibrotic gut tissue.
This project will ultimately offer new molecular targets for the development of possible tailor-made antifibrotic treatments, with likely benefits for healthcare, as it will facilitate the management of severe CD, avoiding surgery and reducing SSN costs.
- Conditions
- Crohn Disease (CD)
- Being tested
- Collection of surgical specimen, Collection of stool sample
- Keywords
- Crohn Disease, Fibrosis, Dysbiosis, Microbiota, Fibrostenosis
- Medical subject headings
- Crohn Disease, Fibrosis, Dysbiosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Collection of surgical specimenProcedure or surgery
Specimens of CD patients and non-IBD related patients will be collected during the surgery performed for clinical practice, without other risks for the patients, since we will use only leftover material after pathologist analysis. All of the collected surgical samples will be used for this project and, for this reason, they will not be conserved after the research period. Any residual samples will be destroyed.
Collection of stool sampleProcedure or surgery
One week before the surgery to remove the stricture, fecal samples from CD patients belonging to B1, B2, B3 groups will be collected. They will be used for the exploratory objective. All of the collected fecal samples will be used for this project and, for this reason, they will not be conserved after the research period. Any residual samples will be destroyed.
| Study group | Role | What they receive |
|---|---|---|
| CD Patients | CD patients with established diagnosis and additionally classified according to 3 stages: B1 (more inflammatory, non-stricturing), B2 (stricturing, non-penetrating) and B3 (stricturing and penetrating). Patients will be stratified on the basis of CT, MRI or ultrasound analysis (stratification already known before surgery) Receives: Procedure: Collection of surgical specimen; Procedure: Collection of stool sample | |
| Non-IBD Patients | Patients with other pathologies but not affected by IBD according to the previously reported clinical and endoscopic evaluation criteria (ex. diverticulitis) Receives: Procedure: Collection of surgical specimen; Procedure: Collection of stool sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
To identify the cellular subtypes and molecular pathways impacted by the specific bacterial factors during CD-associated fibrosis.
Control subjects' and CD-derived surgical specimens will be processed to obtain a cell suspension, that will be frozen and stored for the subsequent cell sorting. Frozen CD and healthy cell suspensions will be then thawed and undergo FACS for specific cell markers (CD31 for endothelial cells, EpCam for epithelial cells, CD90 for fibroblasts, CD45 for leukocytes, including CD4 and CD8 for T cells, CD20 for B cells, CD14 and CD163 for macrophages (MΦ), CD11b and c for dendritic cells (DCs). 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.
Measured: Experiments and analysis: 11th to 36th month
Secondary outcomes (1)
To unravel the cellular and molecular mechanisms and dynamics induced by the bacterial factors in 3D models of intestinal fibrosis
We will isolate and sequence RNA of specific cellular subtypes from the phenotype B1, B2, and B3 of fibrotic CD tissues and healthy non-IBD tissues.
We will profile the microbial composition by Metatranscriptomics as well as we will determine both the differential gene expression (DGE) and the Gene Set Enrichment Analysis (GSEA) through transcriptomics.
Moreover, to identify the cellular type(s) where bacterial proteins will be expected to exert the most prominent pro-fibrotic effects, we will set up the transwell-based experimental platform by plating epithelial cells (organoids) and/or endothelial cells, and/or fibroblasts in the upper chamber of the transwell, while lamina propria mononuclear cells (LPMCs) will be plated in the lower chamber
Measured: Experiments and analysis: 11th to 36th month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2024
- Study startApr 2025 (estimated)
- Primary completionJan 2026 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn Disease (CD)Studies 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Collaborators
- University of Florence, Humanitas Research Hospital IRCCS, Rozzano-Milan, Ministero dell'Istruzione, dell'Università e della Ricerca, Università Vita-Salute San Raffaele
- Responsible party
- Principal investigator, Silvio Danese, IRCCS San Raffaele
- Investigators
- Silvio Danese, PhD-MD, Principal investigator, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06720961
- Sponsor's protocol ID
- PRIN-2022RKE4L
- Other IDs
- Bando MUR 2022 PRIN-2022RKE4L
- Status last verified
- Feb 2025
- First submitted
- 3 Dec 2024
- Last updated
- 14 Feb 2025
- 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 14 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unveiling the Microbial Impact on Intestinal Fibrosis and the Associated Immune Microenvironment: New Insights for the Pathogenesis and Treatment of Crohn's Disease-associated Complications
- ClinicalTrials.gov ID
- NCT06720961
- Acronym / sponsor ID
- PRIN-2022RKE4L
- Conditions
- Crohn Disease (CD)
- Keywords
- Crohn Disease, Fibrosis, Dysbiosis, Microbiota, Fibrostenosis
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Collaborators
- University of Florence, Humanitas Research Hospital IRCCS, Rozzano-Milan, Ministero dell'Istruzione, dell'Università e della Ricerca, Università Vita-Salute San Raffaele
- Study start
- Apr 2025 (estimated)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 6 Dec 2024 (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 goal of this study is to find out if there is a direct connection between an imbalance of gut bacteria and the development of scar tissue in the gut by identifying important bacterial proteins found in scarred gut tissue. Our aim is to identify which types of cells and biological processes are affected by these bacterial proteins in people with Crohn's Disease. We will also study how these bacterial proteins cause changes in 3D models of gut fibrosis.
Detailed description
More than 50% of CD patients develop a penetrating disease or stenosis due to fibrostenosis, which in most cases requires surgery, as no effective therapies have yet been found. The disease leads to both structural and functional alterations of the intestinal mucosa. Although the functional alteration of the mucosa is mainly caused by the continuous tissue damage that occurs during the chronic inflammation associated with CD, recent studies have suggested that the fibrosis associated with CD may be driven by triggering factors independent of inflammation, such as dysbiosis of the microbiota. Our proposal aims to establish the causal link between gut dysbiosis and fibrosis by studying the role of key bacterial proteins present in fibrotic gut tissue.
This project will ultimately offer new molecular targets for the development of possible tailor-made antifibrotic treatments, with likely benefits for healthcare, as it will facilitate the management of severe CD, avoiding surgery and reducing SSN costs.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CD Patients | – | Procedure: Collection of surgical specimen, Procedure: Collection of stool sampleCD patients with established diagnosis and additionally classified according to 3 stages: B1 (more inflammatory, non-stricturing), B2 (stricturing, non-penetrating) and B3 (stricturing and penetrating). Patients will be stratified on the basis of CT, MRI or ultrasound analysis (stratification already known before surgery) |
| Non-IBD Patients | – | Procedure: Collection of surgical specimen, Procedure: Collection of stool samplePatients with other pathologies but not affected by IBD according to the previously reported clinical and endoscopic evaluation criteria (ex. diverticulitis) |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- We will enroll 15 CD patients and 5 patients without IBD-related diseases (ex. diverticulitis) undergoing surgery according to the normal clinical practice for a total of 20 patients as following: - 15 patients with CD (5 patients/stage: B1 (more inflammatory, non-structuring), B2 (structuring, non-penetrating) and B3 (structuring and penetrating). Patients will be stratified according to CT, MRI or ultrasound analysis (stratification already known before surgery) - 5 patients without IBD-related diseases (e.g. diverticulitis) All patients will be recruited only from San Raffaele Hospital (OSR). The participation is voluntary and the patient is allowed to refuse further participation in the protocol whenever he/she wants. Participation in the study will not change the diagnostic-therapeutic treatment that patients undergo following the clinical practice, since patients will continue to be treated in accordance with clinical practice regardless of the results of this study.
Key inclusion criteria (5 listed)
- Adult patients ≥18 and <70 years
- Patients able to autonomously sign the informed consent
- Non pregnant or breastfeeding patients
- For CD patients: CD patients with established diagnosis and additionally classified according to 3 stages: B1 (more inflammatory, non-stricturing), B2 (stricturing, non-penetrating) and B3 (stricturing and penetrating). Patients will be stratified on the basis of CT, MRI or ultrasound analysis (stratification already known before surgery)
- For non-IBD patients: patients with other pathologies but not affected by IBD according to the previously reported clinical and endoscopic evaluation criteria (ex. diverticulitis)
Key exclusion criteria (4 listed)
- Patients <18 years or > 70 years
- Pregnant or breastfeeding patients
- For CD Patients: Subjects with CD who do not meet evaluation criteria described above
- For non-IBD patients: Patients undergoing anti-inflammatory and/or immunosuppressive treatments for IBD-related diseases
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 |
|---|---|---|
| Collection of surgical specimenSpecimens of CD patients and non-IBD related patients will be collected during the surgery performed for clinical practice, without other risks for the patients, since we will use only leftover material after pathologist analysis. All of the collected surgical samples will be used for this project and, for this reason, they will not be conserved after the research period. Any residual samples will be destroyed. | Procedure or surgery | CD Patients, Non-IBD Patients |
| Collection of stool sampleOne week before the surgery to remove the stricture, fecal samples from CD patients belonging to B1, B2, B3 groups will be collected. They will be used for the exploratory objective. All of the collected fecal samples will be used for this project and, for this reason, they will not be conserved after the research period. Any residual samples will be destroyed. | Procedure or surgery | CD Patients, Non-IBD Patients |
Primary outcome
To identify the cellular subtypes and molecular pathways impacted by the specific bacterial factors during CD-associated fibrosis.
Time frame: Experiments and analysis: 11th to 36th month
Control subjects' and CD-derived surgical specimens will be processed to obtain a cell suspension, that will be frozen and stored for the subsequent cell sorting. Frozen CD and healthy cell suspensions will be then thawed and undergo FACS for specific cell markers (CD31 for endothelial cells, EpCam for epithelial cells, CD90 for fibroblasts, CD45 for leukocytes, including CD4 and CD8 for T cells, CD20 for B cells, CD14 and CD163 for macrophages (MΦ), CD11b and c for dendritic cells (DCs). 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.
1 secondary outcome
To unravel the cellular and molecular mechanisms and dynamics induced by the bacterial factors in 3D models of intestinal fibrosis
Time frame: Experiments and analysis: 11th to 36th month
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2025.
- 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.
Silvio Danese, PhD-MD principal investigator
IRCCS San Raffaele
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 (CD), 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 5 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: opening soon, as of the sponsor's last update on 14 Feb 2025. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Silvio Danese, PhD.-MD (+39 0226432807, danese.silvio@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To identify the cellular subtypes and molecular pathways impacted by the specific bacterial factors during CD-associated fibrosis. (time frame: Experiments and analysis: 11th to 36th month). 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 14 Feb 2025.