Clinical Research Directory

TNFi Plus Low-Dose Upadacitinib vs TNFi Intensification in Crohn's Disease With Suboptimal Response

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.

Study of Concordance Between Inflammatory Activity Assessed by Enteric MRI With and Without Intestinal Distension Product in Patients With Ileal 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. We 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.

Qualitative Exploration of Key Symptoms of Stricturing Crohn's Disease: Toward the Development of a Clinical Assessment Score.

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

Evaluation of Muscle Strength and Muscle Mass in Patients With Inflammatory Bowel Disease

This prospective observational study aims to evaluate the validity of ultrasonographic muscle measurements in patients with inflammatory bowel disease (IBD). Sarcopenia is commonly assessed using computed tomography (CT)-based skeletal muscle area measurements at the L3 vertebral level, which are considered a gold standard method. However, CT is not always feasible due to radiation exposure and accessibility limitations. In this study, muscle strength will be assessed using handgrip dynamometry, and muscle mass will be evaluated using ultrasonography of selected skeletal muscles. In patients with available recent abdominal CT imaging, L3 skeletal muscle area will be recorded. The primary objective is to compare ultrasonographic muscle measurements with CT-based assessments and to evaluate the agreement between these methods. This study aims to determine whether ultrasonography can serve as a practical and reliable alternative tool for muscle mass evaluation in patients with IBD.

Health-Related Quality of Life Among Patients With Inflammatory Bowel Disease

The primary aim of this study is to assess HRQOL and its associated factors among people with IBD. The target sample will be 385 adult patients diagnosed with IBD (both Crohn's Disease and Ulcerative Colitis). The data will be collected using a self-administered survey.

Virtual hIStology of Crohn's Disease Ex-vivo Resected Anatomical Lesions

Crohn's disease is a chronic, incurable inflammatory bowel disease with an unpredictable course, characterized by alternating remission and inflammatory flares. Current follow-up strategies are poorly suited to early flare detection, leading to uncontrolled disease progression and complications. A major clinical challenge is distinguishing reversible inflammatory activity from irreversible intestinal fibrosis, as existing imaging techniques lack specificity. This study aims to perform comprehensive ex vivo multiparametric MRI, combined with biophysical measurements and histopathology, on resected intestinal specimens to precisely map inflammation and fibrosis and to validate in vivo MRI-derived biomarkers for personalized therapeutic decision-making.

HB-adMSCs for the Treatment of Crohn's Disease

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

Safety and Efficiency of the Universal CNK-UT009 in Difficult-to-treat Inflammatory Bowel Disease Patients

Inflammatory bowel disease patients who failed from at least two types of biologics or suffered refractory after at least twice surgery are defiened as difficult-to-treat IBD. It is reported a low five-year suvival rate around 15% of difficult-to-treat IBD patients. Cell therapy is a promising new strategy in auto-immune diseases beyond malignant cancers. Inbalanced immune microenvironment contribute to IBD and cell therapy should be a brighting selection of difficult-to-treat IBD. CNK-UT009 is an universal cellular immunotherapy targeted to auto-reactive T cells whose safety and effect were proved in patients with GVHD and type 1 diabetes mellius. Here, we conducted a single-arm open-label exploratory clinical study of CNK-UT cell therapy on difficult-to-treat IBD patients, mainly to explore the safety and define the maximum tolerated dose. Besides, the preliminary effect would also be evaluated.

Switching to the IL-23 Inhibitor Guselkumab for People With Active IBD Who Previously Used Ustekinumab (SHIFT-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.

ALPCO/Calprotectin CLIA Assay: Expected Values of Calprotectin in Healthy Subjects

This study is evaluating the levels of calprotectin, a protein found in stool, in healthy adults. Calprotectin is a marker of inflammation in the intestines and can help doctors tell the difference between inflammatory bowel diseases (IBD), like Crohn's disease or ulcerative colitis, and non-inflammatory conditions like irritable bowel syndrome (IBS). In this study, healthy volunteers aged 22 and older will collect a stool sample at home using a simple kit and mail it to the study site. The samples will be tested using a new laboratory method called the ALPCO Calprotectin CLIA assay. The goal is to confirm what level of calprotectin is considered "normal" in people without intestinal disease. Participation involves just one stool sample, and there are no medical procedures. Volunteers will be compensated for their time. The study will help improve how doctors interpret calprotectin test results in clinical settings.

A Prospective Randomised Study of Treatment Selection Based on Epigenetic Markers Versus Standard of Care Treatment Selection in Adults With CROHN's Disease

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).

Impact of Exclusion Diet in Addition to Anti-TNF Therapy in Crohn's Disease and Ulcerative Colitis: a Prospective, Randomized, Double-arm, Open-label Study

This clinical study protocol aims to prospectively compare the efficacy of standard therapy with anti-TNF agents combined with the Crohn's Disease Exclusion Diet (CDED) versus anti-TNF therapy alone in adult patients with active Crohn's disease or ulcerative colitis. The study will involve patients starting therapy with anti-TNF agents due to active Crohn's disease or ulcerative colitis as per standard clinical practice and in accordance with European (ECCO) guidelines. One group will receive standard medical therapy only, the other will additionally receive dietary advice on how to adhere on a specific exclusion diet, the CDED. By prospectively evaluating the impact of this combined approach, the study seeks to provide evidence on whether CDED can improve response to treatment and therefore improve quality of life for patients with Crohn's disease and ulcerative colitis.

Fluorescence Imaging of Adalimumab-680LT and Risankizumab-800CW in Inflammatory Bowel Disease

Inflammatory bowel diseases (IBD) are chronic relapsing inflammatory disorders of the gastrointestinal tract affecting 2.5 million patients in Europe alone. The majority of newly diagnosed patients are in adolescence or early adulthood and in the midst of their family life, career, and social development. IBD comes with significant morbidity and complex treatment strategies and is associated with a high social burden and medical costs. Besides other factors, the pathogenesis of IBD is attributed to proinflammatory cytokine tumor necrosis factor α (TNFα) and Interleukin 23 (IL-23). Adalimumab, a human monoclonal anti-TNF antibody, and risankizumab, a humanized monoclonal anti-IL-23 antibody, are used to treat patients with moderate to severely active IBD. However, IBD patients often only partially respond to such biological immunomodulating therapies, resulting in high primary nonresponse (30-60%) and loss of response over time (48-58%). The investigators are currently missing reliable tools for response prediction because the limitations of current technologies do not allow the visualization of the molecular phenotype or heterogeneity within patients. Therefore, patients are potentially exposed to a non-effective treatment and its potential side effects while clinical deterioration is ongoing. In addition, it remains completely unknown for most biologicals used for IBD therapy whether they reach their actual targets in the tissue and if a sufficient local concentration is present to achieve treatment response. To develop a predictive tool for assessment of therapeutic (non-)response to patients and gain insights into local drug concentrations in individual patients before initiating anti-TNF or anti-IL23 therapy, the University Medical Center Groningen (UMCG), fluorescently labeled adalimumab (adalimumab-680LT) and risankizumab (risankizumab-800CW) to visualize and quantify the labeled drugs in diseased tissue with dedicated optical fluorescence imaging systems. In previous studies, the investigators have proven that those tracers bind to TNFα/IL23 in the mucosa after intravenous injection and that the investigators can investigate the drug distribution in vivo due to the colocalization of the fluorescently labeled compound. The aim of this follow-up study is to assess the feasibility of simultaneous dual wavelength imaging of adalimumab-680LT and risankizumab-800CW at baseline and evaluate target saturation after at least 14 weeks of adalimumab or risankizumab therapy. The investigators will also use in vivo and ex vivo fluorescence molecular imaging (FMI) to visualize tracer target cells and the patient's molecular phenotype for potential treatment response prediction in IBD patients in the future. The investigators will determine the feasibility of dual wavelengths molecular fluorescence imaging using the GMPproduced near-infrared fluorescent tracers adalimumab-680LT and risankizumab-800CW for visualizing medicine distribution in and ex vivo IBD patients with dedicated fluorescence imaging systems. Furthermore, the investigators will evaluate TNF and IL23 target saturation after 14 weeks of adalimumab or risankizumab therapy and characterize the tissue microenvironment where the drug is abundant and identify potential drug target cells.

Combining Nutritional Therapy and Anti-TNFα Treatment in Pediatric Patients With Crohn's Disease

Children with Crohn's disease (CD), a type of Inflammatory Bowel Disease (IBD), often face serious health challenges, including poor growth, frequent hospital stays, and long-term medication use. Although biologic drugs like infliximab, an anti-TNFα (Tumor necrosis factor α) medication, have improved treatment, they don't work for everyone: many children still experience symptoms or disease flare-ups. Nutritional therapies, especially the Crohn's Disease Exclusion Diet (CDED), may help improve treatment outcomes. This study will assess whether starting CDED at the same time as infliximab leads to better responses to treatment. The goal of this study is to improve how well children respond to therapy, reduce drug exposure, and support better long-term health.

CEDUR - German IBD Registry

The CEDUR registry systematically collects real-world data on inflammatory bowel disease (IBD) patients in Germany. The registry aims to assess quality of care, disease activity, treatment effectiveness, safety, and pharmacoeconomic aspects under routine clinical conditions.

Prospective Risk Evaluation and Detection of Crohn's Disease in First-degree Relatives

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.

Kinetics of Transmural Healing in Patients With Crohns Disease Treated With Risankizumab (SKYRIZI®)

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that can highly alter patients' quality of life and lead to bowel damage due to its transmural pattern. The current guidelines recommend to use treat-to-target strategies to achieve the combination of steroid-free clinical remission and endoscopic remission. However, the implementation of these strategies and endpoints are limited by the need of repeated colonoscopies, which dramatically reduced patients' acceptability and adherence to such a management. The concept of transmural healing has emerged as a promising therapeutic target. It has been associated with longer time spent in steroid-free clinical remission, decreased risk of hospitalization, slower progression of bowel damage and reduced risk of subsequent surgery. Furthermore, recent works suggested that transmural healing could lead to better outcomes, such as prevention of bowel damage progression, than endoscopic remission. Recently, the DEVISE-CD project proposed validated definitions of transmural healing and response (TR50 and TR25) using the modified Clermont score (C-score). Thus, transmural healing will become the next reference target in the near future. Although most data were generated using MRI, intestinal ultrasound (IUS) is an interesting alternative to assess transmural response thanks to its lower cost and high patients' acceptability enabling repeated procedures. IUS is now part of routine practice in day-care units. Recently, Risankizumab, the first in-class anti-IL23 targeting p19 subunit in CD, demonstrated high level of efficacy to achieve and maintain clinical and endoscopic remission. However, no data are hitherto available on the kinetics and the efficacy of risankizumab to achieve transmural healing.

De-escalation of Ustekinumab Therapy in Patients With Crohn's Disease and Ulcerative Colitis

The goal of this clinical trial is to evaluate whether disease remission can be maintained when biologic therapy is reduced in patients with Crohn"s disease (CD) and ulcerative colitis (UC) taking ustekinumab (UST). The main question it aims to answer is: Can we de-escalate UST subcutaneous dose either from every 4 weeks (Q4) to every 8 weeks (Q8) or every 8 weeks (Q8) to every 12 weeks (Q12) in CD or UC patients in deep remission without loosing their response? Researchers will follow UST blood levels, inflammation markers and intestinal mucosa integrity and to see if UST dose can be reduced while maintaining clinical remission. Participants will: Change UST dosing from Q4 to Q8 or from Q8 to Q12. Visit the clinic once every 12 weeks for checkups and tests.

Food Limitations In Crohn's Disease and Ulcerative coliTis

The goal of this clinical trial is to increase the knowledge on what type of diet affects inflammation and how to better convay that information in patients with inflammatory bowel disease (IBD) and decrease selective eating in patients with IBD. The main questions it aims to answer are: * will the use of calprotectin as a control for changes in inflammation decrease selective food choices? * will the use of a digital information tool increase quality of life (QoL) och decrease selctive eating patterns? * will a diet based on nordic food choices decrease inflammation and increase QoL? Researchers will compare with IBD-patients in ordinary care. Participants will eat a test diet during six weeks or go through a digital information tool.

Modafinil For Fatigue in IBD: A Feasibility Randomised Controlled Trial

Fatigue is a big problem in people with inflammatory bowel disease (IBD). Even when IBD is well controlled, 50% of patients remain fatigued most of the time. Fatigue can be physical (e.g. feeling tired or weak) and mental (e.g. brain fog). However, there are no effective treatments for IBD fatigue. Modafinil is a medication that can rapidly improve fatigue. It usually acts within 30 minutes and improves wakefulness. It can also improve brain fog. Modafinil has been used for over 30 years in people with narcolepsy, which is a condition where people fall asleep during the day. Modafinil has also been used in people who do not have narcolepsy. This study will compare modafinil with a dummy tablet (placebo) in people with IBD. This is a feasibility study. This means it primarily aims to test whether a trial like this can be conducted in people with IBD. Half of the patients in the study will receive modafinil and half will receive placebo. Treatment will be 12 weeks. Patients will start by taking 1 tablet and will then increase to 2 tablets and then 3 tablets if needed. A computer will randomly allocate treatment, meaning there is an equal chance of being allocated modafinil or placebo. They will be followed up after 6 weeks and 12 weeks. Being a feasibility study, the investigators will measure how many patients consent to the study; how many complete treatment; and how acceptable the treatment is. Participants will complete a range of questionnaires measuring fatigue, mental health and gut health, primarily to look at the completeness and spread of data, and to obtain estimates of treatment effects and their variance. If feasible, this study will support a larger version of the trial.

Efficacy of MIrikizumab to Achieve Transmural Healing in patiENTs With Crohn's Disease

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

Clostridium Butyricum in Stenosing Crohn's Desease

Crohn's disease is a condition of unknown etiology with an immune-mediated pathogenesis. The subgroup of Crohn's disease with a stricturing phenotype represents a particular challenge for clinicians, as currently no effective medical therapies are available for the prevention or treatment of fibrosis. Autophagy is a key mechanism in the regulation of cellular homeostasis, and preliminary reports from our group and others have suggested a potential role in the pathogenesis of fibrostenotic complications in Crohn's disease. The next-generation probiotic Clostridium butyricum has recently been proposed as a treatment option in several conditions, including inflammatory bowel diseases (IBD). Its beneficial effects are mainly exerted through the production of butyric acid, which in turn plays important roles at the intestinal mucosal level, including the stimulation of autophagy. The possibility of stimulating autophagy in patients with stricturing Crohn's disease may represent a promising therapeutic approach for the prevention and treatment of fibrosis. This study involves the collection of biopsy and blood samples from 40 patients with stricturing Crohn's disease undergoing colonoscopy. In the two months preceding colonoscopy, patients will be randomized into four groups: Patients treated with C. butyricum Patients treated with the autophagy stimulator trehalose Patients treated with C. butyricum + trehalose Patients treated with placebo Laboratory analyses will be performed on biopsy and blood samples to evaluate and quantify molecular mediators involved in inflammation, fibrosis, and autophagy.

Real-World Study on Fecal Microbiota Transplantation: Long-Term Effectiveness and Safety Statistics

This is a large-scale observational study aiming to evaluate the long-term effectiveness and safety of Fecal Microbiota Transplantation (FMT). FMT is a procedure that transfers gut bacteria from healthy donors to patients to restore a balanced gut microbiome. The study will follow approximately 4,000 patients who have received or will receive FMT for conditions like recurrent C. difficile infection, inflammatory bowel disease, functional gastrointestinal disorders, and certain neurological conditions. The main goals are to: * Assess the disease remission rates at 3 months, 1 year, and 5 years after FMT. * Monitor the long-term safety and any potential side effects. * Identify factors that may influence how well a patient responds to the treatment. This research will use both existing patient data (retrospective cohort) and newly collected data from future patients (prospective cohort). The findings are expected to help improve and standardize FMT treatment for better patient care.

Evaluation of Therapeutic Strategy to Prevent Crohn's Disease Endoscopic poSToperatIve recurreNce Based on earlY Dosage of Faecal Calprotectin

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.