None listed
Conditions
Brief summary
UC is a destructive chronic inflammatory disorder of the gastrointestinal tract. Children have a 30 to 40% colectomy rate at 10 years (1). Paediatric onset UC accounts for 15 to 20% of all UC patients (1). Disease is extensive, pancolitis in 60-80% of children occurs twice as frequent as in adults (1). Currently, the pathogenesis of UC is unknown. It is thought that a complex dysregulated immune response to gut microflora plays a major role. Different phenotypes of UC appear to respond to different medical therapies. In particular, two phenotypes, that of moderate-severe UC and PSC-UC, have demonstrated response to newer "biologic agents" like anti-Tumour Necrosis Factor-alpha antibodies and oral vancomycin respectively. Biologics are considered for children with Acute severe presentations not responding to steroids and for chronic refractory UC, uncontrolled by aminosalicylates and thiopurines(1). Indeed, 5-10% of patients with UC require acute surgical intervention because of fulminant colitis refractory to medical therapy (1). Similarly, Antibiotics have gained interest in the management of Colitis, and in small study reported by our group, Vancomycin has shown significant improvement, even complete mucosal healing of the colitis associated with Primary Sclerosing Cholangitis, PSC-UC. There has also been improvement in blood tests of liver inflammation although the significance of these liver improvements remain to be determined.(2). PSC in conjunction with UC, whilst associated with milder bowel disease can lead to to liver cirrhosis, colorectal cancer and cholangiocarcinoma (1. However, these two therapies are new and the mechanisms and impact on mucosal healing and regain of liver function is not yet quantified. We propose to study these evolving treatment modalities in an open label study of patients with UC, including those with PSC-UC who are failing conventional therapies (5-ASA and/or immunosuppression). Children with UC considered for biologics and children with PSC-UC and considering oral Vancomycin will be considered for this study. Consistent with our current clinical practice, at initial enrolment and after 3 months therapy we will systematically assess: patients clinical characteristics, inflammatory markers (CRP, fecal calprotectin), mucosal healing by endoscopy and colonoscopy and features of PSC on Magnetic Resonance Cholangio Pancteatography (MRCP) in those with PSC-UC. We will also collect an additional 10 biopsies at each colonoscopy, each 1-2mm (consistent with our other Ethically approved biopsy study in Crohn's Disease with no additional risk) to assess activity of populations of white blood cells and microflora. Under GA, blood will be obtained to assess IBD genetic mutations. Stool for microbiome will be collected at same time as for faecal calprotectin, a clinical disease marker.
Interventions
This is an observation of clinical practice and determination of key alterations in immunomodulation, biomarkers and and gut microflora between those responding and not responding to Vancomycin and Infliximab with UC.
Patients with moderate to severe Ulcerative Colitis will be exposed to the drug Infliximab and patients with primary sclerosing cholangitis- ulcerative colitis will be exposed the antibiotic vancomycin. The duration of this observation period will be 5 years.
The treatment receive
This is an observation of clinical practice and determination of key alterations in immunomodulation, biomarkers and and gut microflora between those responding and not responding to Vancomycin and Infliximab with UC. Patients with moderate to severe Ulcerative Colitis will be exposed to the drug Infliximab and patients with primary sclerosing cholangitis- ulcerative colitis will be exposed the antibiotic vancomycin. The duration of this observation period will be 5 years. The treatment received by participants is as per standard of care and is not affected by enrolment in this study. Patients would receive the same treatment with or without the presence of the study.
Sponsors
Associate Professor Peter Lewindon
Eligibility
Sex/Gender
All
Age
6 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
Children must have either of the following conditions: Paediatric Primary Sclerosing Cholangitis- Ulcerative Colitis and are to be treated with Vancomycin Paediatric Moderate Severe- Ulcerative Colitis and are to be treated with Infliximab
Exclusion criteria
Children who are not requiring treatment for primary sclerosing cholangitis- ulcerative colitis with vancomycin and moderate to severe ulcerative colitis with biologics will be excluded from the trial
Outcome results
None listed