Clinical Research Directory

Afimkibart (RO7790121) for the Treatment of Moderate to Severe Active Crohn's Disease

This Phase 2, randomized, double-blind, multicenter, induction and maintenance study is designed to evaluate the safety and efficacy of Afimkibart (RO7790121, RVT-3101) in adult participants with moderate to severe active Crohn's disease.

Virtual Versus Dye-based Chromoendoscopy in Inflammatory Bowel Disease Surveillance Colonoscopy

People with inflammatory bowel disease (IBD), such as ulcerative colitis or Crohn's disease affecting the colon, have a higher risk of developing colon cancer over time. To catch early signs of cancer, regular colonoscopies are recommended. In this study, the investigators are comparing two advanced methods of examining the colon during these surveillance colonoscopies. One method uses a special dye sprayed inside the colon to highlight abnormal areas (called dye-based chromoendoscopy). The other method uses new technology built into the camera to enhance the view without needing any dye (called virtual chromoendoscopy). Both methods use modern, high-definition equipment. The purpose of this study is to find out if the newer, dye-free method is as good as the traditional dye method at detecting pre-cancerous changes (called dysplasia) in people with IBD. Adults with IBD who are due for a routine surveillance colonoscopy may be invited to take part. Participants will be randomly assigned to one of the two methods. No additional procedures are involved, and only the way the colon is viewed differs. The investigators will also look at how long the procedures take, how many biopsies are needed, any complications, and how patients experience the exam. Participants will be followed over time using national health records to check for long-term outcomes. This research will help doctors better understand which method is most effective and comfortable for patients, and may guide future recommendations for cancer screening in people with IBD.

Prospective Evaluation of the Carbon Footprint and Clinical Utility of IBUS Compared to Colonoscopy and Enterography in UC and CD

Healthcare contributes approximately 4.4% of global GHG emissions, with diagnostic imaging and endoscopic services being substantial contributors. Colonoscopy and cross-sectional imaging modalities, though indispensable, are associated with high carbon emissions due to electricity use, waste, sterilisation, and transportation. IBUS, a non-invasive, real-time diagnostic modality, is increasingly validated for disease activity assessment in both UC and CD.

A Long-term Extension (LTE) Study of Guselkumab in Pediatric Participants

The purpose of this study is to evaluate long-term safety of subcutaneous guselkumab in pediatric participants with moderately to severely active ulcerative colitis, or moderately to severely active Crohn's disease, or juvenile psoriatic arthritis (jPsA).

A Study of Surgical Interventions in Fistulizing Conditions

In this study, participants with complex fistulizing conditions will be treated with surgical interventions according to their clinic's standard practice. The aim of the study is to generate real-world evidence on standard of care for surgical interventions and related outcomes when treating complex fistulizing conditions. The study sponsor will not be involved in how participants are treated but will provide instructions on how the clinics will record what happens during the study.

Oral N-acetylglucosamine in Crohn's Disease

Protein glycosylation is a critical post-translational modification that regulates protein trafficking and protein-protein interactions impacting a host of physiological processes. There is a growing appreciation of glycosylation defects in chronic human diseases, including Crohns disease. Crohns disease (CD), and the related condition of ulcerative colitis, are chronic inflammatory bowel diseases (IBD) that impact 3.1 million Americans. While the development of medications has revolutionized care of CD patients, clinical remission is only achieved in \~40% of patients a therapeutic ceiling that has not changed in 20 years. These data underscore the need for new CD treatment strategies. The investigators are focused on understanding the role of defective N-glycosylation in CD, as an innovative strategy to identify and develop new therapeutics. Depending on ancestral background, 7-25% of CD patients carry a pathogenic, missense mutation in the manganese (Mn) transporter ZIP8 (rs13107325; ZIP8 A391T). ZIP8 regulates systemic Mn homeostasis with ZIP8 391-Thr causing a relative Mn insufficiency. Mn is a required metal cofactor for enzymes regulating key cellular processes, like N-glycosylation. In the gut, protein N-glycosylation plays key roles in host-pathogen interactions, inflammation, and cell-cell interactions. The investigator's central hypothesis is that in patients carrying ZIP8 391-Thr - CD is exacerbated by aberrant N-glycosylation and that this defect can be targeted by specific, safe therapy. Supporting this hypothesis, Mn levels are reduced (\~15%) in ZIP8 391-Thr allele carriers and this is associated with a decrease in complex N-glycan branching in plasma. Further, the investigators uncovered a microbiota signature in the ileal mucosa that implicated altered bile acid homeostasis in ZIP8 391-Thr carriers. To better understand CD in ZIP8 391 carriers, the investigators generated a knock-in mouse model of ZIP8 391-Thr (Zip8393T/393T). Like patient data, the investigators observe reduced branching of N-glycans and disrupted bile acid homeostasis in the Zip8393T/393T mice. Promising human trials have shown that defects in N-glycan branching can be safely restored by raising levels of the rate-limiting metabolite UDP-N-acetylglucosamine (GlcNAc) via supplementation with free GlcNAc. The investigator's preliminary data in Zip8393T/393T mice have demonstrated that GlcNAc supplementation restores N-glycan branching deficits, rescues the defect in bile acid homeostasis, and ameliorates colitis susceptibility. Thus, the objective of the proposed research is to test a safe and effective therapy for patients carrying ZIP8 391-Thr and others who may have underlying changes in N-glycosylation. The investigators will perform a multi-center, randomized, double-blind, placebo-controlled cross-over study to test the safety and tolerability of oral GlcNAc as a proof-of-concept study. The investigators will use two cohorts stratified by ZIP8 391-Thr genotype status (carriers and non-carriers, n= 20 participants in each cohort, total= 40 participants).

Magnesium in Gastrointestinal Disease

Individuals with gastrointestinal diseases - such as Crohn's disease, ulcerative colitis, ileostomy, or bile acid diarrhoea - are at increased risk of magnesium deficiency. Magnesium is a vital mineral that supports many essential functions in the body, including muscle contraction, nerve signalling, heart rhythm, and bone health. Deficiency may contribute to fatigue, muscle cramps, abnormal heart rhythms, and reduce the quality of life. The purpose of this study is to investigate the prevalence of magnesium deficiency in individuals with these conditions and to identify the most accurate and practical methods for assessing magnesium status in clinical care. Although plasma magnesium is commonly used in routine blood tests, it represents only about 1% of the body's total magnesium and may not reflect true magnesium levels within cells or tissues. Hence, this study compares several different ways of measuring magnesium, including: * Plasma magnesium * Magnesium levels in red and white blood cells (PBMC, RBC, and buffy coat) * Magnesium levels in muscle tissue (via biopsy) * A magnesium retention test, based on how much magnesium is excreted after an infusion The study includes four groups: 1. Patients with inflammatory bowel disease. 2. Patients with an ileostomy. 3. Patients with bile acid diarrhoea. 4. Healthy individuals (control group). All participants will provide blood and urine samples, and some may undergo optional biopsies of muscle or intestinal tissue. Participants will also complete questionnaires and undergo tests of muscle strength and body composition. The findings are expected to enhance the understanding and detection of magnesium deficiency in patients with gastrointestinal diseases and to aid in the development of more effective tools for identifying and treating this common yet often overlooked condition.

Pregnant Women With and Without Crohns Disease to Explore the Role of Plastics and Toxins in Intestinal Inflammation

The PLANET Study aims to determine the impact of microplastics on intestinal inflammation and gut microbiome in order to understand the role of this pollutant on the risk of developing inflammatory bowel disease (IBD) as well as other diseases. With this information, the researchers hope to characterize better the role of environmental pollutants on IBD and develop novel strategies towards prevention.

Treatment of Moderate to Severe Refractory Crohn's Disease

This research study is testing an investigational research product called TRX103 as a possible treatment for individuals suffering from Crohn's Disease (CD). The primary purpose of this study is to learn how safe and effective different doses of TRX103 are when administered to individuals with CD.

OPTImization of Inflammatory Bowel Disease Treatment Through Understanding of Gut VIRome Heterogeneity

Title: The Role of Good Viruses in Inflammatory Bowel Disease Background An imbalance in the bacteria in the gut - called gut dysbiosis - is linked to chronic bowel diseases such as Crohn's disease and ulcerative colitis (IBD). A special and more severe form of IBD, called primary sclerosing cholangitis-associated IBD (PSC-IBD), affects both the gut and the bile ducts, and in serious cases can lead to liver failure. There is currently no cure for IBD. Research suggests that microorganisms in the gut, especially bacteria and viruses called bacteriophages, play an important role in how the disease develops. Treatment with stool from healthy donors, known as fecal microbiota transplantation (FMT), has proven effective against certain infections and has shown promising results in IBD. A newer and possibly safer method is fecal virome transplantation (FVT), where only the virus part (the gut virome) of the stool is used. Bacteriophages can kill harmful bacteria and help restore balance in the gut, but their use is still experimental. Therefore, we aim to develop a new treatment by growing bacteriophages from healthy individuals in the lab and using them to restore a healthy balance of bacteria and viruses in the gut of patients with IBD. Purpose of the study The long-term goal of the study is to improve treatment for IBD by gaining a better understanding of differences in the gut virome between IBD patients and healthy people. We also want to explore whether "fermented" bacteriophages from donor stool can be developed into a future bacteriophage-based therapy. This will be studied using experimental lab setups and animal models. The study will include 10 healthy stool donors and 30 IBD patients (10 with ulcerative colitis, 10 with Crohn's disease, and 10 with PSC-IBD). The study does not involve any treatments - only the collection of biological samples and access to information about your health from your medical record.

Development of a Novel Endoscopic Index and Patient-reported Outcome Measure for Clinical Trials in Participants With Permanent Ileostomy

To date, patients with Crohn's Disease (CD) and permanent ileostomies have been excluded from clinical trials for new treatments. To allow this patient population to be included in clinical trials, outcome and measurement tools are needed. This study aims to develop a Patient Reported Outcome (PRO) and Endoscopic Index (EI) for patients with Crohn's Disease (CD) and permanent ileostomy. The study will enroll about 50 participants and collect videos of endoscopies that are done as part of standard of care. The videos will be centrally read to identify features that represent a broad range of inflammation and will be used to develop the EI. Participants will also be asked to participate in interviews, to understand the symptoms and impacts that are most important to participants for the development of a PRO.

Protease Regulation and Impact of Sodium as Mechanisms of Inflammation in IBD

The study looks at how eating salt affects gut health in people with Crohn's disease. The aim of the study is to find out whether eating more salt increases the breakdown of proteins in the gut and if this makes inflammation and symptoms worse. By studying the link between salt, gut bacteria and inflammation, the study hopes to improve diet advice for people with Crohn's disease. This research may help find specific foods that affect the disease and lead to better, more personalized nutrition plans.

Evaluating the Efficacy and Safety of Mirikizumab in Adults Over 60 With Moderate to Severe Crohn's Disease and Ulcerative Colitis

This research study looks at how safe and effective a medicine called Mirikizumab is for treating older adults (aged 60 and above) who have moderate to severe Crohn's disease (CD) or ulcerative colitis (UC). These two conditions, known as inflammatory bowel diseases (IBD), cause inflammation (swelling and irritation) in the digestive tract. Older adults with these conditions often have other health issues and face increased risks and complications, making it challenging for them to use certain treatments. Mirikizumab is already approved by the FDA for adults with IBD, but there's limited information about how well it works specifically for older adults. This study aims to fill that gap by seeing if Mirikizumab can help these patients safely manage their condition. The study plans to enroll around 150 people from various locations across the United States. Everyone participating will receive Mirikizumab according to the standard, FDA-approved guidelines. The main goal is to see how many participants achieve clinical remission, meaning their symptoms significantly improve or disappear, after 24 weeks of treatment. Researchers will also look at whether this remission lasts up to 48 weeks, how well symptoms are controlled without steroids, how treatment affects indicators of inflammation (such as blood tests), and how the participants feel overall based on their own reports. The safety of Mirikizumab will also be closely monitored throughout the study by regularly checking for any side effects. This study hopes to provide clearer information to help older adults with IBD and their doctors make better treatment decisions, ultimately improving health outcomes and quality of life.

A Study to Evaluate the Effect of Fecal Transplant and Dietary Changes on Disease Activity in Patients With Crohn Disease on Advanced Therapies

Advanced therapies including biologics and small molecules target specific inflammatory pathways. IBD's multifactorial etiology means that blocking a single pathway may not be sufficient for all patients. Even when combination of advanced therapies are used, the incremental benefits often diminish, reflecting the therapeutic ceiling. Furthermore, safety concerns also limit the potential to push beyond this ceiling. Increasing the dose or adding more immunosuppressive agents can lead to a higher risk of infections, malignancies, and other adverse effects, making it impractical to continually intensify treatment. Understanding the therapeutic ceiling in IBD highlights the need for innovative approaches that go beyond current strategies. Given the diverse microbial and immunological landscapes in IBD combining fecal microbiota transplantation (FMT) and Crohn's Disease Exclusion Diet (CDED) with advanced therapies represents a promising approach to break the therapeutic ceiling in CD. This strategy leverages the complementary mechanisms of action of FMT/CDED and advance therapies, potentially offering a more comprehensive treatment modality that addresses the complex and multifactorial nature of IBD. FMT involves the transfer of gut microbiota from a healthy donor to a patient, aiming to restore a balanced microbial community in the intestines. This can help modulate the immune system and reduce inflammation, which are central to Crohn's disease pathology. This study seeks to provide evidence on whether addition of microbiota manipulation by FMT and CDED offers additional benefits when used alongside advance therapies in active CD. The findings from this RCT are expected to significantly enhance treatment strategies, ensuring that patients receive the most effective and appropriate care based on robust scientific evidence. This multi-center double blind placebo-controlled RCT will randomize patients in 1:1:1:1 ratio to FMT, CDED and advance therapy vs sham FMT with advance therapy and CDED vs FMT, Advance therapy and sham diet vs Advance therapy with sham FMT and sham diet for induction and maintenance of remission in patients of active Crohn's disease. Randomization will be held centrally to ensure concealment of allocation. Random numbers will be generated by computerized random number schedule (The RAND), and the randomization list and numbered packing of the intervention will be prepared by a person not involved in the study. Randomization will be performed using permuted blocks of 8. Both the patient and the investigator will be blinded to the intervention

Development and Validation of a New Paediatric Inflammatory Bowel Disease NUTrition Risk Score (PIBD-NUTS)

Children with inflammatory bowel disease (IBD) including both Crohn's disease (CD) and ulcerative colitis (UC) can be at high risk of developing malnutrition due to the nature of their condition. It is also believed that some children with IBD, in need of nutritional care, are not identified quickly by their healthcare professionals. This may negatively affect their nutrition, disease progression and general well-being. Hence, it has been proposed that nutritional screening tools or scores (NSTs) should be used to promptly identify children needing further dietetic review and input. Although there are a few NSTs for generic use in sick children at hospital admission, NSTs or scores to use for children with IBD are currently missing. In this study, we would like to test the performance of an existing tool that is routinely used for all sick children at hospital admission (The Paediatric Yorkhill Malnutrition Score or PYMS)(5) and test whether PYMS can detect children with IBD who are at risk of malnutrition. If PYMS doesn't work well, we will develop a specific tool for children with IBD (The Paediatric IBD Nutrition Score or PIBD-NUTS).