Inflammatory Bowel Disease (Crohn's Disease; Ulcerative Colitis)TOL-IBDNCT07740499
TOLerogenic Potential of Hematopoietic Stem and Progenitor Cells and Inflammatory Bowel Disease
An observational study of Inflammatory Bowel Disease (Crohn's Disease; Ulcerative Colitis), run by IRCCS San Raffaele at 2 sites in Italy.
Trial summary
Pediatric refractory Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, not responsive to current treatments. Since hematopoietic stem and progenitor cells (HSPCs) in the bone marrow display immunomodulatory functions and IL-10-producing regulatory cells regulate gut… Read more about this study
- Who is it for?
- Ages 2 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Inflammatory Bowel Disease (Crohn's Disease; Ulcerative Colitis)
- What is being tested?
- biological sample collection: an additional volume of peripheral blood (3-10 ml), biological sample collection: small fragment (1-5 mm) of intestinal tissue - residual or leftover material and biological sample collection: leftover peripheral blood samples from healthy subjects
- Type of treatment
- Surgery or procedure
- How many people
- 80 participants
- Where
- 2 sitesItaly
- Study dates
- Oct 2026to Nov 2029
- 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 2 to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: Eligible participants will be consecutively enrolled as they present to the clinical centers until the planned sample size is achieved. The Study will include pediatric subjects, both males and females belonging to the following study populations: 1. IBD patients: pediatric patients with chronic intestinal inflammation (i.e., inflammatory bowel disease (IBD), including Crohn Disease, Ulcerative Colitis) at diagnosis or follow-up (including responders to standard of care and refractory to treatment); 2. Non-IBD patients: patients with rectal bleeding with a negative colonoscopy and the exclusion of any inflammatory disorders of the gastrointestinal tract; 3. Healthy controls: healthy volunteers participating in the TIGET09 study protocol ("Collection of biological samples for the study of blood cells and their microenvironment, and for the development of novel therapeutic approaches for genetic diseases and cancer."), as control population.
Who may be able to join
- For all groups:
- Written informed consent from parent(s)/legal guardian(s);
- Sex: Males and Females;
- Age: ≥2 years and <18 years.
- For study group 1:
- Subjects with suspected or confirmed IBD diagnosis.
Show all 11Show fewer
- For study group 2:
- Subjects with rectal bleeding w/o inflammatory disorders of the gastrointestinal tract.
- For study group 3:
- Written consent for participation to TIGET09 study protocol;
- healthy subjects, without known immunodeficiencies, autoimmune, inflammatory or genetic diseases, undergoing genetic, hematological, hematochemical, or HLA compatibility screenings and participating in the TIGET09 study protocol (Title: "Collection of biological samples for the study of blood cells and their microenvironment, and for the development of novel therapeutic approaches for genetic diseases and cancer").
Who cannot join
- For all groups:
- Refusal or inability of the parent(s) or legal guardian(s) to provide written informed consent;
- Age: <2 years and ≥18 years;
- Presence of any medical, psychiatric, or clinical condition that, in the opinion of the clinician, may interfere with participation in the study or interpretation of the study results;
- For study group 1:
- patients without IBD diagnosis or suspect;
Show all 20Show fewer
- For study group 2:
- Subjects without rectal bleeding or with known inflammatory/autoimmune disorders of the gastrointestinal tract.
- For all groups:
- Refusal or inability of the parent(s) or legal guardian(s) to provide written informed consent;
- Age: <2 years and ≥18 years;
- Presence of any medical, psychiatric, or clinical condition that, in the opinion of the clinician, may interfere with participation in the study or interpretation of the study results;
- For study group 1:
- patients without IBD diagnosis or suspect;
- For study group 2:
- Subjects without rectal bleeding or with known inflammatory/autoimmune disorders of the gastrointestinal tract.
- For study group 3:
- Lack of written consent for participation to TIGET09 study protocol;
- patients belonging to study groups 1 and 2; patients with immunodeficiencies, autoimmune, inflammatory or genetic diseases;
- subjects with signs of systemic inflammation.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy2 sites
Pediatric Immunohematology Unit, IRCCS Ospedale San Raffaele
Milan, 20132
Federica Barzaghi, MD, +390226432979, barzaghi.federica@hsr.it
UOC Pediatria, Azienda Ospedaliero-Universitaria Sant'Andrea
Rome, 00189
Giovanni Di Nardo, MD, +390633775971, giovanni.dinardo@uniroma1.it
About this study
Official title: Exploring and Exploiting the TOLerogenic Potential of Hematopoietic Stem and Progenitor Cells to Cure Pediatric Inflammatory Bowel Disease
Pediatric refractory Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, not responsive to current treatments. Since hematopoietic stem and progenitor cells (HSPCs) in the bone marrow display immunomodulatory functions and IL-10-producing regulatory cells regulate gut homeostasis, by combining state-of-the-art strategies for the ex-vivo manipulation and expansion of HSPCs and gene delivery systems to drive HLA-class II-restricted antigen presentation and expression of tolerogenic molecules, the investigators propose to dissect the antigen- (Ag-) presenting capacity of HSPCs and to exploit their tolerogenic potential to induce IL-10-mediated tolerance in the intestinal mucosa of IBD patients. The investigators hypothesize that HSPCs can be engineered using commensal-derived Ags w/wo IL-10 to drive the differentiation of Tr1 cells with the desired Ag-specificity to control intestinal inflammation in IBD. The results of this study will pave the way for defining innovative cell-based approaches for treating refractory pediatric IBD.
Read the detailed description
Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract, with Crohn's Disease (CD) and Ulcerative Colitis (UC) being the main types. The causes of IBD are complex and include immune dysregulation with activation of immune cells, release of inflammatory cytokines, and intestinal tissue damage. Despite significant advances in the treatment of pediatric IBD, a large unmet need for a definitive cure remains, and cell immunotherapy is under investigation. The investigators are specifically interested in refractory IBD, a chronic active condition requiring continuous treatment for symptom relief, with detrimental side effects. Despite the several treatment options currently available, 30% of pediatric IBD patients are refractory, and none of the existing treatments results in complete remission.
Interleukin 10 (IL-10) is an immunoregulatory cytokine associated with IBD pathogenesis and regulating gut homeostasis. Type 1 regulatory T (Tr1) cells produce IL-10 and their function is crucial for suppression of inflammation in IBD. The investigators recently published that antigen (Ag)-specific immune responses in Celiac Disease can be controlled via IL-10-producing Ag-presenting cells engineered to express a gliadin epitope, demonstrating that Ag-presenting cells can be manipulated to promote Tr1 cell differentiation.
Significant advances in the field of hematopoietic stem and progenitor cells (HSPCs) engineering and biology have been achieved. The development of protocols for ex-vivo manipulation and expansion of circulating (c)HSPCs and of mobilization-based chemotherapy-free approaches broadens the applicability of HSPC-based therapies to diseases for which HSPC transplantation is not the standard of care. A recent report showed that Tr1 cells can be promoted by immunogenic HSPC, which present Ags via HLA class II to CD4+ T cells in the bone marrow. This discovery opens new avenues for the development of approaches exploiting the Ag-presenting capacity and the tolerogenic potential of HSPCs to counteract inflammation in target tissues.
Based on these premises, with the final goal of developing a procedure for the induction of IL-10-mediated tolerance to control intestinal inflammation in refractory IBD pediatric patients, the investigators will:
- Investigate the type and frequency of inflammatory and regulatory immune cells, including IL-10-related regulatory cells, infiltrating the gut mucosa of IBD and non-IBD control patients. Results will indicate whether enforcement of the regulatory arm would benefit IBD patients. To this aim, it is necessary to collect and analyze intestinal tissue fragments from IBD and non-IBD control patients.
- Investigate the type and frequency of immune cells, including IL-10-related regulatory cells, circulating in the peripheral blood of IBD patients and non-IBD control patients. Results will indicate whether enforcement of the regulatory arm would benefit IBD patients. To this aim it is necessary to collect PB from IBD and non-IBD control patients.
- Characterize the presence, phenotype, and expansion potential of CD34+ HSPCs circulating in the peripheral blood of IBD patients. To this end, the investigators will collect peripheral blood from IBD patients, and i) assess the frequency, composition, and Ag-presenting potential of and ii) apply ex-vivo expansion and engineering protocols to CD34+ HSPC circulating in the peripheral blood of IBD patients. These results will be pivotal for assessing the feasibility of HSPC-based approaches to restore homeostasis in the intestinal tissue in refractory pediatric IBD.
- Evaluate the response to commensal-derived Ags (e.g., Bacteroides-derived peptides) of CD4+ T lymphocytes circulating by collecting the peripheral blood of IBD patients, non-IBD control patients, and healthy subjects as control. These results will indicate which Ag could be used for HSPC engineering and for inducing IL-10-producing regulatory T cells.
- Assess the ability of human HSPCs to promote Ag-specific Tr1 cells in vitro. To this end, selected IBD patients known to be responders commensal -derived Ags (as above) and peripheral blood will be collected at 1 year (6-18 months) follow-up. The investigators will engineer circulating HSPCs ex-vivo expanded from the peripheral blood of selected IBD patients and test for their ability to promote Ag-specific Tr1 cell upon in vitro culture with autologous CD4+ T cells.
- Being tested
- biological sample collection: an additional volume of peripheral blood (3-10 ml), biological sample collection: small fragment (1-5 mm) of intestinal tissue - residual or leftover material, biological sample collection: leftover peripheral blood samples from healthy subjects
- Keywords
- hematopoietic stem and progenitor cells (HSPCs), immune tolerance, regulatory T cells, IL-10 producing cells, commensal-derived epitopes
- Medical subject headings
- Inflammatory Bowel Diseases, Crohn Disease, Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
biological sample collection: an additional volume of peripheral blood (3-10 ml)Procedure or surgery
An additional volume of peripheral blood (3-10 ml) will be obtained in concomitance with clinically indicated procedures
biological sample collection: small fragment (1-5 mm) of intestinal tissue - residual or leftover materialProcedure or surgery
A small fragment (1-5 mm) of intestinal tissue - residual or leftover material -will be obtained from patients undergoing diagnostic or follow-up endoscopy
biological sample collection: leftover peripheral blood samples from healthy subjectsProcedure or surgery
Peripheral blood samples from healthy subjects, leftover from TIGET09 protocol analysis will be collected
| Study group | Role | What they receive |
|---|---|---|
| Study Group 1 | IBD patients: pediatric patients with chronic intestinal inflammation (i.e., inflammatory bowel disease (IBD), including Crohn Disease, Ulcerative Colitis) at diagnosis or follow-up (including responders to standard of care and refractory to treatment) Receives: Procedure: biological sample collection: an additional volume of peripheral blood (3-10 ml); Procedure: biological sample collection: small fragment (1-5 mm) of intestinal tissue - residual or leftover material | |
| Study Group 2 | Non-IBD patients: patients with rectal bleeding with a negative colonoscopy and the exclusion of any inflammatory disorders of the gastrointestinal tract Receives: Procedure: biological sample collection: an additional volume of peripheral blood (3-10 ml); Procedure: biological sample collection: small fragment (1-5 mm) of intestinal tissue - residual or leftover material | |
| Study Group 3 | Healthy volunteers (controls) Receives: Procedure: biological sample collection: leftover peripheral blood samples from healthy subjects |
What is being measured
The primary outcome is the main question the study is designed to answer.
To characterize pediatric IBD patients' peripheral blood and intestinal mucosa immune cell composition
Frequency (%) of predefined regulatory and inflammatory immune-cell subsets in peripheral blood and gut mucosa, including regulatory T cells (FOXP3+ Tregs and IL-10 producing Tr1 cells), T naïve/memory and effector cells, regulatory myeloid cells (DC-10), and inflammatory myeloid cells (cDC1 and cDC2), measured by flow cytometry.
The primary objective will be considered met if patients with IBD show a lower frequency of IL-10-producing cells than controls, with the estimated between-group difference supporting a defect in IL-10-producing cell responses.
Measured: Baseline timepoint
Secondary outcomes (1)
To explore the ability of HSPCs to induce in vitro the differentiation of Ag-specific Tr1 cells.
Induction of Tr1-like cells following T-cell/HSPC co-culture, assessed by: frequency (%) of cells expressing the Tr1-associated phenotype and expression of Tr1-associated genes.
Success criterion (exploratory): Generation of a T-cell population displaying Tr1-associated features.
Measured: Baseline and 1 year follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2026
- Study startOct 2026 (estimated)
- Primary completionOct 2029 (estimated)
- Study completionNov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Inflammatory Bowel Disease (Crohn's Disease; Ulcerative Colitis)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
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Silvia Gregori, IRCCS San Raffaele
- Investigators
- Silvia Gregori, PhD, Principal investigator, IRCCS Ospedale San RaffaeleAlessandro Aiuti, MD, Principal investigator, IRCCS Ospedale San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07740499
- Sponsor's protocol ID
- RF-2024-12378919
- Other IDs
- RF-2024-12378919
- Acronym
- TOL-IBD
- Status last verified
- Jul 2026
- First submitted
- 23 Jul 2026
- Last updated
- 31 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Hernandez-Malmierca P, Vonficht D, Schnell A, Uckelmann HJ, Bollhagen A, Mahmoud MAA, Landua SL, van der Salm E, Trautmann CL, Raffel S, Grunschlager F, Lutz R, Ghosh M, Renders S, Correia N, Donato E, Dixon KO, Hirche C, Andresen C, Robens C, Werner PS, Boch T, Eisel D, Osen W, Pilz F, Przybylla A, Klein C, Buchholz F, Milsom MD, Essers MAG, Eichmuller SB, Hofmann WK, Nowak D, Hubschmann D, Hundemer M, Thiede C, Bullinger L, Muller-Tidow C, Armstrong SA, Trumpp A, Kuchroo VK, Haas S. Antigen presentation safeguards the integrity of the hematopoietic stem cell pool. Cell Stem Cell. 2022 May 5;29(5):760-775.e10. doi: 10.1016/j.stem.2022.04.007.
PubMed 35523139Omer-Javed A, Pedrazzani G, Albano L, Ghaus S, Latroche C, Manzi M, Ferrari S, Fiumara M, Jacob A, Vavassori V, Nonis A, Canarutto D, Naldini L. Mobilization-based chemotherapy-free engraftment of gene-edited human hematopoietic stem cells. Cell. 2022 Jun 23;185(13):2248-2264.e21. doi: 10.1016/j.cell.2022.04.039. Epub 2022 May 25.
PubMed 35617958Capo V, Penna S, Merelli I, Barcella M, Scala S, Basso-Ricci L, Draghici E, Palagano E, Zonari E, Desantis G, Uva P, Cusano R, Sergi Sergi L, Crisafulli L, Moshous D, Stepensky P, Drabko K, Kaya Z, Unal E, Gezdirici A, Menna G, Serafini M, Aiuti A, Locatelli SL, Carlo-Stella C, Schulz AS, Ficara F, Sobacchi C, Gentner B, Villa A. Expanded circulating hematopoietic stem/progenitor cells as novel cell source for the treatment of TCIRG1 osteopetrosis. Haematologica. 2021 Jan 1;106(1):74-86. doi: 10.3324/haematol.2019.238261.
PubMed 31949009Passeri L, Andolfi G, Bassi V, Russo F, Giacomini G, Laudisa C, Marrocco I, Cesana L, Di Stefano M, Fanti L, Sgaramella P, Vitale S, Ziparo C, Auricchio R, Barera G, Di Nardo G, Troncone R, Gianfrani C, Annoni A, Passerini L, Gregori S. Tolerogenic IL-10-engineered dendritic cell-based therapy to restore antigen-specific tolerance in T cell mediated diseases. J Autoimmun. 2023 Jul;138:103051. doi: 10.1016/j.jaut.2023.103051. Epub 2023 May 22.
PubMed 37224733Cook L, Stahl M, Han X, Nazli A, MacDonald KN, Wong MQ, Tsai K, Dizzell S, Jacobson K, Bressler B, Kaushic C, Vallance BA, Steiner TS, Levings MK. Suppressive and Gut-Reparative Functions of Human Type 1 T Regulatory Cells. Gastroenterology. 2019 Dec;157(6):1584-1598. doi: 10.1053/j.gastro.2019.09.002. Epub 2019 Sep 10.
PubMed 31513797Krawiec P, Pawlowska-Kamieniak A, Pac-Kozuchowska E. Interleukin 10 and interleukin 10 receptor in paediatric inflammatory bowel disease: from bench to bedside lesson. J Inflamm (Lond). 2021 Mar 10;18(1):13. doi: 10.1186/s12950-021-00279-3.
PubMed 33691712Parigi TL, D'Amico F, Abreu MT, Dignass A, Dotan I, Magro F, Griffiths AM, Jairath V, Iacucci M, Mantzaris GJ, O'Morain C, Reinisch W, Sachar DB, Turner D, Yamamoto T, Rubin DT, Peyrin-Biroulet L, Ghosh S, Danese S. Difficult-to-treat inflammatory bowel disease: results from an international consensus meeting. Lancet Gastroenterol Hepatol. 2023 Sep;8(9):853-859. doi: 10.1016/S2468-1253(23)00154-1. Epub 2023 Jul 6.
PubMed 37423233Neurath MF, Sands BE, Rieder F. Cellular immunotherapies and immune cell depleting therapies in inflammatory bowel diseases: the next magic bullet? Gut. 2024 Dec 10;74(1):9-14. doi: 10.1136/gutjnl-2024-332919.
PubMed 39025492
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploring and Exploiting the TOLerogenic Potential of Hematopoietic Stem and Progenitor Cells to Cure Pediatric Inflammatory Bowel Disease
- ClinicalTrials.gov ID
- NCT07740499
- Acronym / sponsor ID
- TOL-IBD / RF-2024-12378919
- Keywords
- hematopoietic stem and progenitor cells (HSPCs), immune tolerance, regulatory T cells, IL-10 producing cells, commensal-derived epitopes
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- Oct 2026 (estimated)
- Primary completion
- Oct 2029 (estimated)
- Study completion
- Nov 2029 (estimated)
- First posted
- 31 Jul 2026 (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.
Pediatric refractory Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, not responsive to current treatments. Since hematopoietic stem and progenitor cells (HSPCs) in the bone marrow display immunomodulatory functions and IL-10-producing regulatory cells regulate gut homeostasis, by combining state-of-the-art strategies for the ex-vivo manipulation and expansion of HSPCs and gene delivery systems to drive HLA-class II-restricted antigen presentation and expression of tolerogenic molecules, the investigators propose to dissect the antigen- (Ag-) presenting capacity of HSPCs and to exploit their tolerogenic potential to induce IL-10-mediated tolerance in the intestinal mucosa of IBD patients. The investigators hypothesize that HSPCs can be engineered using commensal-derived Ags w/wo IL-10 to drive the differentiation of Tr1 cells with the desired Ag-specificity to control intestinal inflammation in IBD. The results of this study will pave the way for defining innovative cell-based approaches for treating refractory pediatric IBD.
Detailed description
Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract, with Crohn's Disease (CD) and Ulcerative Colitis (UC) being the main types. The causes of IBD are complex and include immune dysregulation with activation of immune cells, release of inflammatory cytokines, and intestinal tissue damage. Despite significant advances in the treatment of pediatric IBD, a large unmet need for a definitive cure remains, and cell immunotherapy is under investigation. The investigators are specifically interested in refractory IBD, a chronic active condition requiring continuous treatment for symptom relief, with detrimental side effects. Despite the several treatment options currently available, 30% of pediatric IBD patients are refractory, and none of the existing treatments results in complete remission.
Interleukin 10 (IL-10) is an immunoregulatory cytokine associated with IBD pathogenesis and regulating gut homeostasis. Type 1 regulatory T (Tr1) cells produce IL-10 and their function is crucial for suppression of inflammation in IBD. The investigators recently published that antigen (Ag)-specific immune responses in Celiac Disease can be controlled via IL-10-producing Ag-presenting cells engineered to express a gliadin epitope, demonstrating that Ag-presenting cells can be manipulated to promote Tr1 cell differentiation.
Significant advances in the field of hematopoietic stem and progenitor cells (HSPCs) engineering and biology have been achieved. The development of protocols for ex-vivo manipulation and expansion of circulating (c)HSPCs and of mobilization-based chemotherapy-free approaches broadens the applicability of HSPC-based therapies to diseases for which HSPC transplantation is not the standard of care. A recent report showed that Tr1 cells can be promoted by immunogenic HSPC, which present Ags via HLA class II to CD4+ T cells in the bone marrow. This discovery opens new avenues for the development of approaches exploiting the Ag-presenting capacity and the tolerogenic potential of HSPCs to counteract inflammation in target tissues.
Based on these premises, with the final goal of developing a procedure for the induction of IL-10-mediated tolerance to control intestinal inflammation in refractory IBD pediatric patients, the investigators will:
- Investigate the type and frequency of inflammatory and regulatory immune cells, including IL-10-related regulatory cells, infiltrating the gut mucosa of IBD and non-IBD control patients. Results will indicate whether enforcement of the regulatory arm would benefit IBD patients. To this aim, it is necessary to collect and analyze intestinal tissue fragments from IBD and non-IBD control patients.
- Investigate the type and frequency of immune cells, including IL-10-related regulatory cells, circulating in the peripheral blood of IBD patients and non-IBD control patients. Results will indicate whether enforcement of the regulatory arm would benefit IBD patients. To this aim it is necessary to collect PB from IBD and non-IBD control patients.
- Characterize the presence, phenotype, and expansion potential of CD34+ HSPCs circulating in the peripheral blood of IBD patients. To this end, the investigators will collect peripheral blood from IBD patients, and i) assess the frequency, composition, and Ag-presenting potential of and ii) apply ex-vivo expansion and engineering protocols to CD34+ HSPC circulating in the peripheral blood of IBD patients. These results will be pivotal for assessing the feasibility of HSPC-based approaches to restore homeostasis in the intestinal tissue in refractory pediatric IBD.
- Evaluate the response to commensal-derived Ags (e.g., Bacteroides-derived peptides) of CD4+ T lymphocytes circulating by collecting the peripheral blood of IBD patients, non-IBD control patients, and healthy subjects as control. These results will indicate which Ag could be used for HSPC engineering and for inducing IL-10-producing regulatory T cells.
- Assess the ability of human HSPCs to promote Ag-specific Tr1 cells in vitro. To this end, selected IBD patients known to be responders commensal -derived Ags (as above) and peripheral blood will be collected at 1 year (6-18 months) follow-up. The investigators will engineer circulating HSPCs ex-vivo expanded from the peripheral blood of selected IBD patients and test for their ability to promote Ag-specific Tr1 cell upon in vitro culture with autologous CD4+ T cells.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Study Group 1 | – | Procedure: biological sample collection: an additional volume of peripheral blood (3-10 ml), Procedure: biological sample collection: small fragment (1-5 mm) of intestinal tissue - residual or leftover materialIBD patients: pediatric patients with chronic intestinal inflammation (i.e., inflammatory bowel disease (IBD), including Crohn Disease, Ulcerative Colitis) at diagnosis or follow-up (including responders to standard of care and refractory to treatment) |
| Study Group 2 | – | Procedure: biological sample collection: an additional volume of peripheral blood (3-10 ml), Procedure: biological sample collection: small fragment (1-5 mm) of intestinal tissue - residual or leftover materialNon-IBD patients: patients with rectal bleeding with a negative colonoscopy and the exclusion of any inflammatory disorders of the gastrointestinal tract |
| Study Group 3 | – | Procedure: biological sample collection: leftover peripheral blood samples from healthy subjectsHealthy volunteers (controls) |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Eligible participants will be consecutively enrolled as they present to the clinical centers until the planned sample size is achieved. The Study will include pediatric subjects, both males and females belonging to the following study populations: 1. IBD patients: pediatric patients with chronic intestinal inflammation (i.e., inflammatory bowel disease (IBD), including Crohn Disease, Ulcerative Colitis) at diagnosis or follow-up (including responders to standard of care and refractory to treatment); 2. Non-IBD patients: patients with rectal bleeding with a negative colonoscopy and the exclusion of any inflammatory disorders of the gastrointestinal tract; 3. Healthy controls: healthy volunteers participating in the TIGET09 study protocol ("Collection of biological samples for the study of blood cells and their microenvironment, and for the development of novel therapeutic approaches for genetic diseases and cancer."), as control population.
Key inclusion criteria (11 listed)
- Written informed consent from parent(s)/legal guardian(s);
- Sex: Males and Females;
- Age: ≥2 years and <18 years.
- Subjects with suspected or confirmed IBD diagnosis.
- Subjects with rectal bleeding w/o inflammatory disorders of the gastrointestinal tract.
Key exclusion criteria (20 listed)
- Refusal or inability of the parent(s) or legal guardian(s) to provide written informed consent;
- Age: <2 years and ≥18 years;
- Presence of any medical, psychiatric, or clinical condition that, in the opinion of the clinician, may interfere with participation in the study or interpretation of the study results;
- patients without IBD diagnosis or suspect;
- Subjects without rectal bleeding or with known inflammatory/autoimmune disorders of the gastrointestinal tract.
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 |
|---|---|---|
| biological sample collection: an additional volume of peripheral blood (3-10 ml)An additional volume of peripheral blood (3-10 ml) will be obtained in concomitance with clinically indicated procedures | Procedure or surgery | Study Group 1, Study Group 2 |
| biological sample collection: small fragment (1-5 mm) of intestinal tissue - residual or leftover materialA small fragment (1-5 mm) of intestinal tissue - residual or leftover material -will be obtained from patients undergoing diagnostic or follow-up endoscopy | Procedure or surgery | Study Group 1, Study Group 2 |
| biological sample collection: leftover peripheral blood samples from healthy subjectsPeripheral blood samples from healthy subjects, leftover from TIGET09 protocol analysis will be collected | Procedure or surgery | Study Group 3 |
Primary outcome
To characterize pediatric IBD patients' peripheral blood and intestinal mucosa immune cell composition
Time frame: Baseline timepoint
Frequency (%) of predefined regulatory and inflammatory immune-cell subsets in peripheral blood and gut mucosa, including regulatory T cells (FOXP3+ Tregs and IL-10 producing Tr1 cells), T naïve/memory and effector cells, regulatory myeloid cells (DC-10), and inflammatory myeloid cells (cDC1 and cDC2), measured by flow cytometry. The primary objective will be considered met if patients with IBD show a lower frequency of IL-10-producing cells than controls, with the estimated between-group difference supporting a defect in IL-10-producing cell responses.
1 secondary outcome
To explore the ability of HSPCs to induce in vitro the differentiation of Ag-specific Tr1 cells.
Time frame: Baseline and 1 year follow up
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 31 Jul 2026.
- Background: PubMed 35523139Hernandez-Malmierca P, Vonficht D, Schnell A, Uckelmann HJ, Bollhagen A, Mahmoud MAA, Landua SL, van der Salm E, Trautmann CL, Raffel S, Grunschlager F, Lutz R, Ghosh M, Renders S, Correia N, Donato E, Dixon KO, Hirche C, Andresen C, Robens C, Werner PS, Boch T, Eisel D, Osen W, Pilz F, Przybylla A, Klein C, Buchholz F, Milsom MD, Essers MAG, Eichmuller SB, Hofmann WK, Nowak D, Hubschmann D, Hundemer M, Thiede C, Bullinger L, Muller-Tidow C, Armstrong SA, Trumpp A, Kuchroo VK, Haas S. Antigen presentation safeguards the integrity of the hematopoietic stem cell pool. Cell Stem Cell. 2022 May 5;29(5):760-775.e10. doi: 10.1016/j.stem.2022.04.007.
- Background: PubMed 35617958Omer-Javed A, Pedrazzani G, Albano L, Ghaus S, Latroche C, Manzi M, Ferrari S, Fiumara M, Jacob A, Vavassori V, Nonis A, Canarutto D, Naldini L. Mobilization-based chemotherapy-free engraftment of gene-edited human hematopoietic stem cells. Cell. 2022 Jun 23;185(13):2248-2264.e21. doi: 10.1016/j.cell.2022.04.039. Epub 2022 May 25.
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- 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.
Silvia Gregori, PhD principal investigator
IRCCS Ospedale San Raffaele
Alessandro Aiuti, MD principal investigator
IRCCS Ospedale San Raffaele
2 sites 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 Disease (Crohn's Disease; Ulcerative Colitis), run by IRCCS San Raffaele at 2 sites 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 11 inclusion and 20 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 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 Silvia Gregori, PhD (+390226434894, gregori.silvia@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To characterize pediatric IBD patients' peripheral blood and intestinal mucosa immune cell composition (time frame: Baseline timepoint). 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 NCT07740499, which also lists 8 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 31 Jul 2026.