Pouchitis

Ulcerative colitis (UC) is a chronic intestinal disease, often debuting early in life, and affecting the colon and rectum. The therapy is mainly medical and based on 5-aminosalicylic acid (5-ASA) and steroids. The last 20 years numerous new advanced therapies have become available and introduced more and more early after diagnosis. Surgery is still needed in refractory disease and will cure most patients, while ending up with a stoma. There is conflicting data on whether advanced therapies are decreasing the need for surgery or not. Reconstruction of bowel continuity is usually possible but somehow performed in less than 50% of Swedish patients. Restorative proctectomy with ileal pouch (created of the last part of the small bowel) anal anastomosis (IPAA) is gold standard. As of this year it is centralized to 4 units in Sweden. One complication after IPAA is pouchitis, an inflammation in the pouch that behaves like UC. More than half of all patients will have at least one flare of pouchitis, and some will develop chronic or recurrent pouchitis. Recent publications have shown an increased risk of pouchitis after the introduction of advanced therapies, but the reasons for this are still unknown. Prophylactic therapy with 5-ASA after IPAA surgery have been suggested. All patients in Sweden going through IPAA surgery due to UC will be invited to be part of this randomized controlled study to evaluate if 5-ASA can diminish the risk of pouchitis in UC.

The purpose of this research study is to assess the safety and efficacy of fecal microbiota transplant (FMT) in the treatment of chronic pouchitis.

When some people have their large bowel removed, a surgeon can make a "pouch" from part of the small bowel to connect it to the back passage (anus). Pouchitis is when the pouch becomes inflamed (swollen) or infected. The main aim of this study is to find out if vedolizumab improves pouchitis symptoms and pouch inflammation. Other aims include to find out if vedolizumab is well tolerated and if it causes any medical problems (adverse events or side effects) and to look for any changes in the well-being of participants during their treatment with vedolizumab. This study consists of two parts: Part 1 includes the induction and maintenance periods, and Part 2 includes the continued maintenance period. Participants will receive up to 12 infusions of vedolizumab. In Part 1 of the study, first 3 infusions are in first 6 weeks (Day 1, Week 2 and Week 6). Participants who are getting benefit may continue with the treatment for up to 7.5 months (30 weeks) in the maintenance period for Part 1. After completing treatment with vedolizumab in Part 1, participants will visit their clinic for a health check at Week 34. Participants who show clinical response at Week 34 will continue to Part 2, receiving vedolizumab every 8 weeks for an additional 40 weeks, starting at Week 38 and ending with the last dose being at Week 78. Final efficacy assessments, including a pouchoscopy will be performed at Week 82.

Although many people will develop recurrent pouchitis (inflammation of the ileal pouch-anal anastomosis or J-pouch after colectomy for ulcerative colitis) after an initial episode of pouchitis, there are currently no effective treatments to prevent recurrent pouchitis. The goal of this study is to evaluate the potential for rifaximin, an antibiotic, to prevent recurrent pouchitis after treatment for an initial episode of pouchitis. In this study, all patients will be given daily rifaximin for one year after being treated for an initial episode of pouchitis. This study will examine whether people are willing to take rifaximin for one year with the goal of preventing recurrent pouchitis. Additionally, this study will examine whether patients experience any unexpected side effects of rifaximin therapy. The information gained through this study will potentially be helpful in improving the ability to prevent recurrent pouchitis in patients who have a colectomy for ulcerative colitis.

This study will evaluate the effectiveness of hyperbaric oxygen therapy (HBOT) on treating emerging indications (i.e., conditions that have shown to potentially benefit from HBOT) using the Multicenter Registry for Hyperbaric Oxygen Treatment. The study team aims to collect ongoing data on how well HBOT treats these emerging indications, and to add these data to the growing HBO Registry. The research team hypothesizes that HBOT will result in improvements of the condition of the various emerging indications.

The researchers propose conducting a multi-center, randomized, placebo-controlled study to investigate the potential role of etrasimod for the primary and secondary prevention of pouchitis among high-risk patients submitted to total proctocolectomy (TPC) with ileal-pouch anal anastomosis (IPAA) for medically refractory disease. The trial will be conducted in compliance with this protocol, Good Clinical Practice guidelines, and Institutional Review Board requirements.

Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) is considered the procedure of choice in patients with ulcerative colitis (UC) refractory to medical therapy or with neoplasia. The most common complication after IPAA is the development of pouchitis. Pouchitis is clinically characterized by variable symptoms including increased stool frequency, altered consistency, bloody stools, abdominal cramping, urgency, and incontinence. Symptomatic pouchitis longer than four weeks is considered chronic pouchitis. The conventional treatment for acute and chronic pouchitis is antibiotics, such as metronidazole and ciprofloxacin. The disease course of antibiotic responsive pouchitis may evolve into antibiotic dependent (requiring antibiotic maintenance therapy) pouchitis and then antibiotic refractory (no response to antibiotic treatment) pouchitis. Although many patients respond to antibiotic therapy, there is also evidence that suggest that aberrant regulation of the mucosal immune system might play a part in the pathogenesis of pouchitis arising from an abnormal mucosal immune response to a dysbiosis of the pouch microbiota. If individuals fail to respond to antibiotics, anti-tumor necrosis factor (anti-TNF) agents and vedolizumab have been proposed for the treatment of chronic pouchitis. Guselkumab, an interleukin-23 (IL-23) p19 subunit antagonist monoclonal antibody, is proven to be efficacious in patients with moderately-to-severely active UC. Efficacy of guselkumab in treating UC has been shown in multiple large clinical trials. However, patients with pouchitis were never the targeted population and were even often excluded from the trials. Pouchitis becomes a chronic problem with a huge impact in the quality of life of these patients. The incidence of pouchitis has been rising in the last decades. This increase might be explained by a change in dietary habits of this population. This open label single center trial at UZ Leuven aims to evaluate the efficacy and safety of guselkumab in the treatment of chronic antibiotic refractory pouchitis during a 48-week treatment period, with or without a dietary intervention. Twenty subjects with a proctocolectomy and IPAA for UC who have developed chronic or relapsing pouchitis will be enrolled.

The goal of this clinical trial is to learn if mirikizumab works to treat pouch disorders in adults. The main questions it aims to answer are: Does mirikizumab reduce symptoms of pouch disorders Participants will: Take mirikizumab every 4 weeks for one year Visit the clinic once every month for two months and at the end of the study Keep a diary of their symptoms

Patients with a pouch frequently suffer from chronic inflammation of the intestinal tract, called pouchitis. Pouchitis is routienly treated with repeated courses of antibiotics and probiotics, which does not stop the inflammation from recurring and exposes the patients to the risk of developing antibiotic -resistant pouchitis. Experimental data suggest that the effectiveness of the antibiotic and probiotic treatment can be prolonged by high consumption of trypotophan, an aminoacid present in everyday food. The Try Pro Pouch study aims to compare the consumption of high amounts of tryptophan against placebo in patients with pouchitis.