Crohn Disease (CD)

This study will focus on the commonly used non-nutritive sweetener (NNS) sucralose (2 sachets/day resulting in daily dose: sucralose 2.5mg/kg) and its role in changing the gut microbiota in humans with IBD, compared to healthy non-IBD individuals. We will focus on studying IBD patients affected with CD as a proof of principle that could be tested later in other IBD subtype (ulcerative colitis or others specific surgical conditions).

Methodology: Randomized, double-blind, efficacy and safety study of allogeneic HB-adMSCs vs placebo for the treatment of Crohn's Disease with a 16-week treatment period and a safety and efficacy follow up period for 52 weeks post first treatment. Treatment Duration: 16 weeks General Objectives: To assess the efficacy and safety of multiple intravenous infusions of allogeneic HB-adMSCs by improving signs and symptoms of Crohn's Disease in this subject population. Number of Subjects: 46 (23 in each treatment arm) Indication: Crohn's Disease

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that can significantly impair patients' quality of life. Due to its transmural nature (affecting the entire thickness of the intestinal wall), it naturally progresses to intestinal destruction (stenosis, fistula), requiring intestinal resection in approximately half of patients during follow-up. The long-term goal for patients is to maintain a normal life, i.e., without symptoms and without intestinal destruction. To this end, short- and medium-term therapeutic goals have evolved in recent years. Clinical remission is not a sufficient goal, as it has not changed the natural history of the disease. The current goal is to achieve a combination of clinical remission and endoscopic mucosal healing, as this is associated with a reduced risk of adverse outcomes (recurrence of symptoms, hospitalization, intestinal resection). Transmural healing assessed by MRI is also a promising goal associated with a reduced risk of adverse outcomes (recurrence of symptoms, hospitalization, intestinal resection). Furthermore, it is associated with a lower risk of progression to intestinal destruction, unlike endoscopic remission. In this context, transmural healing could soon become the benchmark in terms of therapeutic objectives for Crohn's disease, particularly in the ileum. Although enteric MRI is better accepted than colonoscopy by patients with Crohn's disease, in the ACCEPT1 study, nearly half of patients (48.6%) reported the need to use an intestinal distension product (PEG, mannitol, etc.) as a significant obstacle to repeating entero-MRI, while more than a third complained of vomiting (33.7%) or severe diarrhea (35.0%) induced by these same products. Being able to do without the use of distension products would significantly improve the acceptability of entero-MRI. The investigators hypothesize that an enteric MRI without distension would lead to poorer ileal distension but would allow inflammatory activity scores to be assessed on MRI in a manner similar to an examination with distension, and thus would not impact the need for therapeutic intensification.

The PREDICT-CD study aims to validate a risk score for the development of Crohn's disease, based on serological biomarkers and lifestyle-related factors. Given that having a family member with the disease is the strongest known risk factor, the target population will consist of first-degree relatives (aged 16 to 35) of individuals diagnosed with Crohn's disease. This study will be conducted within Work Package 3 (WP3) of the INTERCEPT project, a consortium funded by the Innovative Health Initiative (IHI). The research will take place across 28 centres in seven countries: Portugal, Spain, France, Italy, the Netherlands, Sweden, and Poland. To achieve the study objectives, individuals with Crohn's disease (referred to as patients) will be invited to participate and to engage their eligible first-degree relatives. At the baseline visit, the patient's physician will complete a clinical questionnaire covering disease history, treatments, and previous interventions. At the same time, first-degree relatives (parents, siblings, or children) will donate a blood sample for serum isolation and, optionally, a whole blood and stool sample. They will also complete a questionnaire regarding their health status, habits, and preferences. Follow-up questionnaires will be administered every six months to monitor the onset of symptoms or behavioural changes.

Inflammatory Bowel Disease (IBD) patients have an increased risk of ColoRectal Cancer (CRC). The cumulative risk of CRC development is estimated at 1% after 10 years of disease progression, 2% after 20 years, and 5% after more than 20 years of disease progression (1). The incidence of CRC in IBD has gradually declined, attributed to enhanced detection of preneoplastic lesions (dysplasia), improved adherence to screening recommendations, utilization of advanced high-definition endoscopes (2-4), and the implementation of more efficacious therapeutic strategies (5-9). Presently, there is no consensus on the endoscopic management of dysplastic lesions. Recent techniques such as submucosal dissection (ESD) enable the resection of non-polypoid flat lesions larger than 2 cm. Lesions previously treated with colectomy can now be resected by ESD with en-bloc resection rates of approximately 85.7% (17). However, long-term data on the risk of local or distant recurrence after endoscopic resection in IBD is lacking. It is crucial to evaluate complete (R0) and curative resection rates, as well as the rate of local recurrence, based on the type of endoscopic treatment. In light of the 21st century advancements, characterized by high-definition endoscopes and targeted treatments, it is imperative to: * Assess the prevalence and incidence of dysplasia in IBD and its risk of progression to CRC. * Specifically characterize the endoscopy and histology of pre-neoplastic lesions in IBD to facilitate better selection of lesions amenable to endoscopic treatment or surgery. * Evaluate the rates of local and distant recurrence over time, considering factors associated with this evolving risk (IBD characteristics, endoscopic appearance, histology, type of resection, etc.).

This study is investigating whether a cranberry-based dietary supplement, rich in polyphenols and fiber, can enhance gut health in individuals with Crohn's disease. People with Crohn's disease often have an imbalance in their gut microbiome (the community of bacteria in the gut). Previous research suggests that cranberry compounds may help support beneficial gut bacteria. In this study, adults with Crohn's disease will be randomly assigned to one of two groups: one group will receive a cranberry supplement to take once daily for 10 weeks, and the other group will receive a placebo (a supplement with no active ingredients). All participants will be asked to complete online questionnaires and collect samples of their blood, urine, and stool at four time points over a total of 15 weeks. These samples will help researchers understand how the cranberry supplement affects the gut microbiome, inflammation, and overall health. Participation is voluntary, and participants can withdraw from the study at any time. The results of this study may help identify new diet-based approaches to improve gut health in individuals with Crohn's disease.

This study explores whether simple nutrition education can help children and teens with inflammatory bowel disease (IBD) eat fewer ultra-processed foods (UPFs). UPFs include packaged snacks, sugary drinks, and fast food-items that are high in added sugars, fats, and artificial ingredients. Participants will complete online food recalls to measure what they eat and will then receive either nutrition handouts alone or handouts plus a short educational video about UPFs. Researchers will compare changes in UPF intake between the two groups after several weeks and ask families how useful and acceptable they found the materials. The goal is to identify an effective, practical way to support healthier eating habits and long-term gut health in pediatric IBD.

The SHIFT-IBD Study is being conducted at multiple medical centers across Canada to evaluate how well guselkumab (Tremfya) works for people with inflammatory bowel disease (IBD) who haven't responded well enough to ustekinumab. Patients will begin guselkumab based on their doctor's decision. If eligible, they may be invited to participate in the study, which involves monitoring symptoms, test results, and overall health over the course of one year. Guselkumab will be given according to local medical guidelines. Doctors can adjust the treatment as needed, just like in routine care. Researchers believe that switching to guselkumab may be as effective as other advanced treatments. For those who saw some improvement on ustekinumab but not enough, guselkumab may offer better symptom control-without worsening results on medical tests like endoscopy. The goal is to explore better treatment options for people whose IBD has not been well controlled with current therapies.

This retrospective cohort study aims to compare the efficacy of different biologics in preventing postoperative endoscopic recurrence in Crohn's disease (CD). It plans to include 198 adult patients who underwent bowel resection and initiated prophylactic biologic therapy between January 1, 2015, and April 1, 2025. Patients will be divided into anti-TNF (e.g., infliximab, adalimumab) and non-anti-TNF (e.g., vedolizumab, ustekinumab) groups based on the biologic started within 6 weeks post-surgery. The primary outcome is endoscopic recurrence (Rutgeerts score ≥ i2) at 6-12 months postoperatively. Secondary outcomes include severe endoscopic recurrence, clinical recurrence, recurrence at different anastomotic sites, CD-related rehospitalization, reoperation, drug persistence, the POCER postoperative endoscopic index, and histopathological changes in the bowel and mesenteric fat. Subgroup analyses will explore treatment effects by recurrence risk stratification and resection extent. Using retrospective data collection, the study will apply multivariate regression and survival analysis to provide real-world evidence for optimizing postoperative biologic selection.

The goal of this observational study is to establish a multicenter prospective clinical and biospecimen platform for biomarker discovery and validation in inflammatory bowel disease, including Crohn's disease and ulcerative colitis. Researchers want to learn whether candidate biomarkers or combined biomarker models can help assess intestinal inflammation, monitor response to routine clinical treatment, predict treatment outcomes, and identify participants who may be at higher risk of disease progression. The study may enroll participants with inflammatory bowel disease, unaffected first-degree relatives of participants with inflammatory bowel disease, unrelated healthy controls, and non-IBD disease controls when appropriate. Clinical information and biological samples, including blood, stool, and intestinal tissue, may be collected. Biomarkers measured in blood, stool, intestinal tissue, genetic data, immune profiles, microbiome data, and other multi-omics data may be evaluated. The main questions this study aims to answer are: Can candidate biomarkers or combined biomarker models identify endoscopic disease activity when compared with endoscopic assessment? Can these biomarkers monitor or predict clinical response, clinical remission, endoscopic response, endoscopic remission, imaging response, or biomarker response during routine clinical care? Can these biomarkers help predict treatment failure, disease progression, hospitalization, surgery, treatment escalation, or complex Crohn's disease phenotypes? Participants will not be assigned to any treatment by the study. All treatments and clinical management decisions will be chosen by treating physicians as part of routine medical care.

Crohn's disease (CD) is a chronic and destructive inflammatory disease of the gastrointestinal tract characterized by phases of relapse and remission. Tumor necrosis factor (TNF) antagonists, anti-integrins and anti-interleukin (IL) 12/23 are the main therapeutic agents to obtain deep remission and prevent disability. Despite the significant advances these biologics represent in treating inflammatory bowel disease (IBD), many patients experience suboptimal responses, including primary non-response or a loss of effectiveness over time, often leading to treatment discontinuation. For all these medications, a dose-response relationship has been demonstrated and an increase in dose or dosing frequency is recommended. Dose escalation is now an essential therapeutic approach necessary in 30 to 50% of CD patients treated with biologics. This strategy, supported by international guidelines, allows for long-term efficacy to be maintained without compromising safety. Guselkumab (GUS) is a monoclonal antibody targeting the p19 subunit of IL-23. In a recent phase III trial (GALAXI), GUS demonstrated superiority of both subcutaneous (SC) maintenance doses (200 mg every 4 weeks \[q4w\] and 100 mg every 8 weeks \[q8w\]) compared to placebo and ustekinumab. In the GALAXI phase III program, at least 30% of patients did not achieve clinical response after a 12-week intravenous induction, and almost 20% experienced a loss of response by week 44. In these patients, the benefit of an intensified dose of GUS (200 mg q4w) maintenance remains to be determined to guide clinicians in optimizing its use in clinical practice. The investigator aimed to evaluate the one-year effectiveness of GUS in CD in real-world settings and under optimal conditions allowing dose intensification.

The aim of this study is to identify HRV changes predictive of IBD flares using patient-own wearable devices in a large cohort supplemented by additional data layers including sleep parameters, step count and clinical data extracted from electronic patient files.

The goal of this observational study is to measure changes in sleep quality before and after starting treatment with advance therapy in adult with Crohn disease. The main question it aims to answer is: what is the association between response to therapy and sleeping patterns? Participants who are about to begin advanced treatment will be asked to wear a Fitbit device before end after treatment initiation to monitor sleep patterns and sleep quality, complete a sleep diary and a sleep quality questionnaire. The follow-up period will last 26 weeks, during which disease severity and response to treatment will be assessed.

This observational study aims to identify genes that may affect how patients with inflammatory bowel disease respond to anti-TNF treatment and why some patients lose response to treatment over time. The study will examine whether genetic markers can help predict which patients are more likely to respond to anti-TNF therapy. Participants who have not previously received anti-TNF treatment and are about to start advanced therapy will provide a blood sample to test for the genetic markers. Participants will also undergo regular assessments of current treatment, disease activity, and inflammatory markers during follow-up.

Perianal fistulizing Crohn's disease (pCD) represents a severe phenotype of Crohn's disease, affecting approximately 20-30% of patients and resulting in chronic drainage, recurrent sepsis, impaired continence, and reduced quality of life. Despite optimization of biologics, antibiotics, and surgical drainage, durable healing remains difficult to achieve. Conventional surgical approaches such as curettage or seton management alone yield modest remission rates, and repeated procedures may compromise sphincter integrity. Autologous mechanically processed tissue stromal vascular fraction (tSVF) is derived from adipose tissue using non enzymatic methods and can be prepared and reinjected during the same operative session. Unlike culture-expanded or enzymatically isolated cell products, mechanical tSVF retains a native adipose micro architecture containing stromal cells, perivascular elements, endothelial progenitors, extracellular matrix components, and bioactive cytokines. This heterogeneous microenvironment is hypothesized to exert immunomodulatory, pro angiogenic, and regenerative effects that may enhance tract healing while preserving sphincter function. Mechanical processing avoids enzymatic digestion, cell expansion, and complex laboratory infrastructure, making it potentially more feasible and cost effective in real world settings. However, high quality prospective data evaluating mechanically processed autologous tSVF specifically in refractory complex pCD remain limited, and feasibility data are required before undertaking a large randomized trial. This single arm pilot feasibility study is therefore designed to evaluate procedural feasibility, safety, and preliminary signals of clinical and radiological healing following mechanical tSVF injection in refractory complex perianal Crohn's disease. The results will inform design parameters, outcome variability, and sample size estimation for a future definitive multicenter trial.

This research study is studying DB-3Q as a possible treatment for medically refractory Crohn's disease. The purpose of this study is to research and evaluate safety and effectiveness of the administration of bone marrow mesenchymal stem cell (bmMSC) derived extracellular vesicles product, DB-3Q, the study drug for Crohn's disease.

This multicenter, randomized, controlled trial aims to evaluate the efficacy and safety of standard-dose tumor necrosis factor inhibitor (TNFi) plus low-dose upadacitinib compared with TNFi dose intensification in patients with moderate-to-severe Crohn's disease who have a suboptimal response to standard-dose TNFi therapy. Eligible participants are adults with active Crohn's disease receiving standard-dose infliximab or adalimumab who remain inadequately controlled despite ongoing treatment. Participants will be randomly assigned in a 1:1 ratio to either continue standard-dose TNFi with oral upadacitinib 15 mg once daily, or receive TNFi dose intensification according to the protocol. Clinical assessments will be performed at baseline and during follow-up, with the primary endpoint assessed at Week 14. The primary outcome is the proportion of participants achieving clinical remission, defined as a Crohn's Disease Activity Index (CDAI) score \<150 at Week 14. Secondary outcomes include clinical response, endoscopic response and remission, changes in inflammatory biomarkers such as C-reactive protein and fecal calprotectin, quality of life, and safety outcomes including adverse events and serious adverse events. Participants will continue follow-up after Week 14 to evaluate treatment durability and longer-term safety. This study is designed to determine whether a dual-target strategy with standard-dose TNFi plus low-dose upadacitinib provides superior short-term efficacy and acceptable safety compared with conventional TNFi intensification in Crohn's disease patients with insufficient benefit from standard-dose TNFi therapy.

The purpose of this research study is to evaluate what type of treatment will be beneficial for people with Crohn's disease and difficult to treat inflammation in the small bowel. Current therapies are used to control the inflammation due to Crohn's disease in your digestive tract. In some patients, those therapies are not sufficient to fully treat the disease. This objective of this study is to evaluate the efficacy of a different type of therapy, tirzepatide, that may promote healing of the affected intestinal segment. To evaluate the efficacy of this medication, a member of the research team will ask patients questions about how they feel and observe whether this medication heals the their bowel at colonoscopy. A member of the research team will also use blood samples, stool samples and samples of the small intestine taken during a colonoscopy to understand how tirzepatide helps heal the intestine.

Crohn's disease (CD) (\> 200,000 patients in France) is a chronic inflammatory disease that can lead to progression of intestinal destruction and impaired quality of life. Despite the widespread use of biotherapies, intestinal resections remain frequent (50% of patients over time). Unfortunately, surgery is not curative since 75% of patients experienced post-endoscopic operative recurrence (POR) (i.e., recurrence of ulcerations) during the first year after surgery. Prevention of endoscopic POR (defined as a Rutgeerts index ≥ i2) is essential because endoscopic POR is highly predictive of clinical POR (i.e., recurrence of CD-related symptoms): \> 40% and \> 80% within 5 years for a Rutgeerts index ≥ i2 or ≥ i3, respectively. The recommended management is to start treatment after surgery to avoid endoscopic POR, and to perform a colonoscopy at 6 months (M6) with therapeutic escalation if endoscopic POR. Despite anti-TNF or ustekinumab treatment, the endoscopic POR rate remains high (30-40% at M6) leading to \> 40% clinical POR despite therapeutic escalation (90 mg/4 weeks with ustekinumab) potentially due to late therapeutic escalation. Innovative strategies are therefore needed to prevent endoscopic POR, such as the use of fecal calprotectin, a non-invasive biomarker associated with endoscopic CD activity. We have previously demonstrated that its variation between surgery and M3 allows for a value at M3 predictive of endoscopic POR at M6. In this study, we hypothesize, for the first time, that a strategy integrating fecal calprotectin measurement at M3 with earlier therapeutic escalation (M3 vs M6) in case of abnormal value or kinetics could decrease the rate of endoscopic POR at M6.

The ADICROHN-3 study is a prospective, multicenter, open-label cohort study. Its design is supported by the following elements: * The results of the ADICROHN pilot study (EudraCT No. 2013-002602-31) and our 3-year study, which demonstrate an excellent safety profile with a promising efficacy signal. * Data from the literature confirming that cryopreservation of FVS does not compromise the clonogenic and differentiation potential of mesenchymal progenitors, nor its regenerative effect. * The ongoing ADICROHN-2 study (PHRC N 2019; EudraCT No. 2019-001948-21) confirming the feasibility of patient recruitment, mastery of the therapeutic approach, and the absence of adverse events related to the experimental treatment. * The opportunity for a second FVS injection for patients initially treated but who did not respond to the treatment. * The opportunity for a first FVS injection in patients in the placebo arm, thereby providing access to an innovative therapy available to patients included in this trial who are untreated and remain refractory to standard care. To avoid compromising the results of the ongoing ADICROHN-2 study, enrolled patients will remain blinded to the treatment arm to which they belonged in the ADICROHN-2 study.

Prospectively study the correlation between Leucine-rich α2-glycoprotein (LRG) and clinical/endoscopic/histological disease activity in patients with inflammatory bowel disease (IBD) in Europe.

This is a multicentre, prospective, randomised, controlled, open-label study to assess the efficacy, safety, and cost-effectiveness of epigenome-guided treatment selection compared to usual standard-of-care (SOC) treatment selection in patients initiating biologic therapy for the treatment of their active Crohn's Disease (CD).

Efficacy of Mirikizumab to achieve transmural healing in patients with Crohn's Disease

The goal of this qualitative study is to identify and better understand the symptoms of stricturing Crohn's disease in order to inform the development of more appropriate clinical evaluation scores. This study focuses on adult patients diagnosed with stricturing Crohn's disease who are followed in hospital gastroenterology departments. The main questions it aims to answer are: * Which symptoms are perceived by patients as the most specific and significant features of stenosing Crohn's disease? * Which symptoms are perceived by patients as early warning signs of a stenosing flare? * How does stenosing Crohn's disease impact daily life, mental health, and quality of life, and what coping strategies do patients use to manage symptoms and limit their impact? Participants will: * Take part in a one-hour individual semi-structured interview, conducted in person (at the hospital, at home, or in another agreed location) or by videoconference * Have the interview audio-recorded for transcription and qualitative analysis * Be offered the opportunity to review and validate the transcript and summary of their interview before final anonymized analysis

Through a pilot randomized controlled trial (RCT), the aim is to test the clinical impact and feasibility of a AI-enhanced Virtual Reality (VR) Cognitive Behavioral therapy (CBT) program versus distraction VR among patients with inflammatory bowel disease (IBD) and anxiety. It is hypothesized that using VR/AI CBT may reduce anxiety and IBD symptoms, leading to improved overall physical, psychological, and social functioning when compared to distraction VR.