Vancomycin Efficacy in Response to Dysbiosis in Atypical Colitis (VERDA)

The goal of this clinical trial is to learn whether oral vancomycin therapy could be used to treat paediatric inflammatory bowel diseases (IBD), particularly atypical ulcerative colitis and ulcerative colitis associated with primary sclerosing cholangitis (PSC-UC). This trial will also investigate how oral vancomycin may affect gut microbiota (the community of bacteria in the gut) and change gut metabolism, influence disease progression, and exhibit overall safety during long-term use.

The main questions it aims to answer are:

1. Does oral vancomycin improve disease activity and lead to remission based on clinical symptoms (PUCAI score), biomarkers (such as faecal calprotectin), imaging, and endoscopy findings?
2. How does oral vancomycin change the gut microbiota and hut metabolism, and are these changes linked to treatment response?
3. Does oral vancomycin improve liver-related outcomes in children with PSC-UC (e.g., liver enzymes and liver stiffness)?
4. Does treatment improve the quality of life of children and their families?
5. What medical problems, side effects, or risks do participants have when taking oral vancomycin, including the development of antibiotic-resistant bacteria?

Researchers will compare groups of children receiving oral vancomycin together with conventional medical treatment (CMT) to those receiving conventional treatment alone in certain patient groups. They will also compare stool and gut metabolims findings with children who have typical ulcerative colitis, and with healthy controls.

The participants will:

• Be children aged 6-15 years who are planned for colonoscopy due to suspected inflammatory bowel disease
• Be assigned to different groups based on their colonoscopy results (e.g., PSC-UC, atypical UC without PSC, typical UC, or healthy controls); children with atypical UC will be randomly assigned to receive oral vancomycin plus conventional treatment or conventional treatment alone
• Take oral vancomycin capsules (if assigned) in addition to standard therapy, typically three times per day, for at least 3 months and up to 12 months depending on treatment response
• Continue standard treatments for IBD (such as mesalazine, thiopurines, or biologics) as part of routine care

Participants will attend clinic visits and follow-ups at baseline (before treatment) and then approximately every 3 months (at 3, 6, 9, and 12 months) while receiving oral vancomycin. After ceasing oral vancomycin, they will be followed-up for another 12 months - up to 2 years after the start of the study

During the study, participants will undergo a range of clinical assessments and tests, including:

• Symptom assessment using the Paediatric Ulcerative Colitis Activity Index (PUCAI)
• Blood tests to monitor inflammation, liver function, and general health
• Stool samples to measure faecal calprotectin and analyse gut microbiota
• Saliva samples to study microbiota composition
• Imaging tests such as intestinal ultrasound (to measure bowel wall thickness) and liver elastography (to assess liver stiffness)
• Magnetic resonance imaging (MRCP) in selected patients to assess bile duct disease
• Endoscopy and biopsies (at baseline and, if needed, during follow-up) to evaluate intestinal inflammation and healing
• Quality-of-life questionnaires completed by the child and/or their parents

Participants taking oral vancomycin will also be closely monitored for:

• side effects, including gastrointestinal symptoms such as nausea or diarrhoea
• Blood and stool testing will help identify potential complications, including development of vancomycin-resistant bacteria
• Treatment may be stopped early if the participant does not respond or if significant side effects occur

Researchers will analyse changes over time in clinical outcomes, microbiota composition, gut metabolism, and laboratory findings to determine whether oral vancomycin is effective and safe. They will also investigate whether changes in the microbiome can predict which patients respond to treatment.

Overall, this study aims to improve understanding of paediatric IBD, especially atypical forms linked to PSC, and to evaluate whether modifying gut bacteria with oral vancomycin can lead to better disease control, improved quality of life, and more personalised treatment strategies for children.