TOLerogenic Potential of Hematopoietic Stem and Progenitor Cells and Inflammatory Bowel Disease

NCT07740499 | Not Yet Recruiting

• 1 other identifier: RF-2024-12378919
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 2

Brief 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 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.

Conditions

Inflammatory Bowel Disease (Crohn's Disease; Ulcerative Colitis)

Keywords

hematopoietic stem and progenitor cells (HSPCs); immune tolerance; regulatory T cells; IL-10 producing cells; commensal-derived epitopes

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline timepoint

Secondary Outcomes (1)

• To explore the ability of HSPCs to induce in vitro the differentiation of Ag-specific Tr1 cells.

  Baseline and 1 year follow up

Study Arms (3)

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)

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

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)

Procedure: biological sample collection: leftover peripheral blood samples from healthy subjects

Interventions

biological sample collection: an additional volume of peripheral blood (3-10 ml) PROCEDURE

An additional volume of peripheral blood (3-10 ml) will be obtained in concomitance with clinically indicated procedures

Study Group 1; Study Group 2

biological sample collection: small fragment (1-5 mm) of intestinal tissue - residual or leftover material PROCEDURE

A small fragment (1-5 mm) of intestinal tissue - residual or leftover material -will be obtained from patients undergoing diagnostic or follow-up endoscopy

Study Group 1; Study Group 2

biological sample collection: leftover peripheral blood samples from healthy subjects PROCEDURE

Peripheral blood samples from healthy subjects, leftover from TIGET09 protocol analysis will be collected

Study Group 3

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.
• 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").

You may not qualify if:

• 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 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:

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (2)

Pediatric Immunohematology Unit, IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

UOC Pediatria, Azienda Ospedaliero-Universitaria Sant'Andrea

Rome, 00189, Italy

Location

Related Publications (8)

• 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.

  PMID: 35523139 BACKGROUND

• Omer-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.

  PMID: 35617958 BACKGROUND

• Capo 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.

  PMID: 31949009 BACKGROUND

• Passeri 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.

  PMID: 37224733 BACKGROUND

• Cook 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.

  PMID: 31513797 BACKGROUND

• Krawiec 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.

  PMID: 33691712 BACKGROUND

• Parigi 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.

  PMID: 37423233 BACKGROUND

• Neurath 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.

  PMID: 39025492 BACKGROUND

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases

Study Officials

• Silvia Gregori, PhD

  IRCCS Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

• Alessandro Aiuti, MD

  IRCCS Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Silvia Gregori, PhD

CONTACT

+390226434894; gregori.silvia@hsr.it

Laura Passerini, PhD

CONTACT

+390226439303; passerini.laura@hsr.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 23, 2026
• First Posted: July 31, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): November 1, 2029
• Last Updated: July 31, 2026

Record last verified: 2026-07

Locations

IT (2)