TOLerogenic Potential of Hematopoietic Stem and Progenitor Cells and Inflammatory Bowel Disease
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age2-18
SponsorIRCCS San Raffaele
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Written informed consent from parent(s)/legal guardian(s);
Sex: Males and Females;
Age: ≥2 years and <18 years.
Written consent for participation to TIGET09 study protocol;
Disqualifiers
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;
Refusal or inability of the parent(s) or legal guardian(s) to provide written informed consent;
Trial 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.
Trial design
Design model
Case-control
Time perspective
Prospective
Treatments tested in this trial
biological sample collection: an additional volume of peripheral blood (3-10 ml)
Procedure/SurgeryAn 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 material
Procedure/SurgeryA 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 subjects
Procedure/SurgeryPeripheral blood samples from healthy subjects, leftover from TIGET09 protocol analysis will be collected
Treatment groups
80 Participants
are divided into 3 treatment groupsGroup A: Study Group 12 interventions
Group B: Study Group 22 interventions
Group C: Study Group 31 intervention
Trial outcomes
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.
Time frame
Baseline timepointSecondary 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.
Time frame
Baseline and 1 year follow upSponsors and contacts
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Source ClinicalTrials.gov
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