Protocol for a randomised, placebo-controlled pilot study for assessing feasibility and efficacy of faecal microbiota transplantation in a paediatric ulcerative colitis population: PediFETCh trial

Nikhil Pai, Jelena Popov, Nikhil Pai, Jelena Popov

Abstract

Introduction: Ulcerative colitis (UC) is a chronic, relapsing condition characterised by colonic inflammation. Increasing prevalence in early-age diagnosis provides opportunities for additional complications in later life as a result of prolonged exposure to inflammatory and therapeutic insults, necessitating novel avenues for therapeutics which may result in fewer side effects. Faecal microbiota transplantation (FMT) has previously demonstrated potential therapeutic benefit in an adult randomised-controlled trial and several recurrent Clostridium difficile infection studies. This phase Ib pilot will be the first randomised, single-blinded, placebo-controlled trial to assess feasibility and patient outcomes in a paediatric inflammatory bowel disease (IBD) population.

Methods and analysis: Fifty patients will be randomised 1:1 to receive normal saline control or active sample. Enema administrations will be performed two times per week for 6 weeks, followed at a 6-month follow-up period. Feasibility outcomes will include measures of patient eligibility, recruitment, willingness to participate, samples collections, hospitalizations and drop-out rate. Improvements in disease symptoms will determine the efficacy of treatment. Clinical disease scores will be taken throughout the study period using the Paediatric Ulcerative Colitis Activity Index (PUCAI). Monitoring of inflammatory markers in blood and stool will be performed at regular intervals. Microbiome analysis will be conducted on stool samples collected throughout the trials period. Imaging and endoscopic surveillance will be conducted if clinically necessary.

Ethics and dissemination: Ethics was obtained from local hospital research ethics boards across all three sites. Health Canada and FDA approval was obtained for the use of an Investigatory New Drug product. Results from this trial will be presented in international conferences and published in peer-review journals.

Trial registration number: Trial registration number: NCT02487238; preresults.

Keywords: IBD; fecal microbiota transplantation; microbiome; pediatrics; treatment.

Conflict of interest statement

Competing interests: None declared.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
Study protocol. IBD-U,inflammatory bowel disease-unclassified; PUCAI, Paediatric Ulcerative Colitis Activity Index; UC, ulcerative colitis.

References

    1. Rocchi A, Benchimol EI, Bernstein CN, et al. . Inflammatory bowel disease: a canadian burden of illness review. Can J Gastroenterol 2012;26:811–7. 10.1155/2012/984575
    1. Kappelman MD, Rifas-Shiman SL, Kleinman K, et al. . The prevalence and geographic distribution of crohn's disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol 2007;5:1424–9. 10.1016/j.cgh.2007.07.012
    1. Benchimol EI, Bernstein CN, Bitton A, et al. . Trends in epidemiology of pediatric inflammatory bowel disease in Canada: Distributed network analysis of multiple population-based provincial health administrative databases. Am J Gastroenterol 2017. 10.1038/ajg.2017.97
    1. El Mouzan MI, Al Mofarreh MA, Saadah OI, et al. . Impact of pediatric inflammatory bowel disease on linear growth: data from a national cohort study in Saudi Arabia. Saudi J Gastroenterol 2016;22:396–8. 10.4103/1319-3767.191147
    1. Sanderson IR. Growth problems in children with IBD. Nat Rev Gastroenterol Hepatol 2014;11 10.1038/nrgastro.2014.102
    1. Fuller-Thomson E, Sulman J. Depression and inflammatory bowel disease: findings from two nationally representative canadian surveys. Inflamm Bowel Dis 2006;12:697–707. 10.1097/00054725-200608000-00005
    1. de Ridder L, Turner D, Wilson DC, et al. . Malignancy and mortality in pediatric patients with inflammatory bowel disease: a multinational study from the porto pediatric IBD group. Inflamm Bowel Dis 2014;20:291–300. 10.1097/01.MIB.0000439066.69340.3c
    1. Talley NJ, Abreu MT, Achkar JP, et al. . American College of Gastroenterology IBD Task Force. An evidence-based systematic review on medical therapies for inflammatory bowel disease. Am J Gastroenterol 2011;106:S2–S25. 10.1038/ajg.2011.58
    1. Torres J, Danese S, Colombel JF. New therapeutic avenues in ulcerative colitis: thinking out of the box. Gut 2013;62:1642–52. 10.1136/gutjnl-2012-303959
    1. Kassam Z, Lee CH, Yuan Y, et al. . Fecal Microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol 2013;108:500–8. 10.1038/ajg.2013.59
    1. Michail S, Durbin M, Turner D, et al. . Alterations in the gut microbiome of children with severe ulcerative colitis. Inflamm Bowel Dis 2012;18:1799–808. 10.1002/ibd.22860
    1. Nell S, Suerbaum S, Josenhans C. The impact of the Microbiota on the pathogenesis of IBD: lessons from mouse infection models. Nat Rev Microbiol 2010;8:564–77. 10.1038/nrmicro2403
    1. Kunde S, Pham A, Bonczyk S, et al. . Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis. J Pediatr Gastroenterol Nutr 2013;56:597–601. 10.1097/MPG.0b013e318292fa0d
    1. Kellermayer R, Nagy-Szakal D, Harris RA, et al. . Serial fecal Microbiota transplantation alters mucosal gene expression in pediatric ulcerative colitis. Am J Gastroenterol 2015;110:604–6. 10.1038/ajg.2015.19
    1. Suskind DL, Brittnacher MJ, Wahbeh G, et al. . Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active crohn's disease. Inflamm Bowel Dis 2015;21:556–63. 10.1097/MIB.0000000000000307
    1. Suskind DL, Singh N, Nielson H, et al. . Fecal microbial transplant via nasogastric tube for active pediatric ulcerative colitis. J Pediatr Gastroenterol Nutr 2015;60:27–9. 10.1097/MPG.0000000000000544
    1. Vandenplas Y, Veereman G, van der Werff Ten Bosch J, et al. . Fecal microbial transplantation in early onset colitis: caution advised. J Pediatr Gastroenterol Nutr 2015;61:e12–14. 10.1097/MPG.0000000000000281
    1. Shimizu H, Arai K, Abe J, Nakabayashi K, et al. . Repeated fecal microbiota transplantation in a child with ulcerative colitis. Pediatr Int 2016;58:781–5. 10.1111/ped.12967
    1. Kumagai H, Yokoyama K, Imagawa T, et al. . Failure of fecal Microbiota transplantation in a Three-Year-Old child with severe refractory ulcerative colitis. Pediatr Gastroenterol Hepatol Nutr 2016;19:214–20. 10.5223/pghn.2016.19.3.214
    1. Moayyedi P, Surette MG, Kim PT, et al. . Fecal Microbiota transplantation induces remission in patients with active ulcerative colitis in a Randomized Controlled Trial. Gastroenterology 2015;149:102–9. 10.1053/j.gastro.2015.04.001
    1. Turner D, Otley AR, Mack D, et al. . Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology 2007;133:423–32. 10.1053/j.gastro.2007.05.029
    1. Turner D, Mack DR, Hyams J, et al. . C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) or both? A systematic evaluation in pediatric ulcerative colitis. J Crohns Colitis 2011;5:423–9. 10.1016/j.crohns.2011.05.003
    1. Turner D, Levine A, Escher JC, et al. . Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-based consensus guidelines. J Pediatr Gastroenterol Nutr 2012;55:340–61. 10.1097/MPG.0b013e3182662233
    1. Snapper SB. Very-Early-Onset inflammatory bowel disease. Gastroenterol Hepatol 2015;11:554–6.
    1. Turner D, Muise AM. Very Early Onset IBD: how very Different 'on Average'? J Crohns Colitis 2017;11:jjw217–2. 10.1093/ecco-jcc/jjw217
    1. Kelly CR, Ihunnah C, Fischer M, et al. . Fecal Microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol 2014;109:1065–71. 10.1038/ajg.2014.133
    1. Benchimol EI, Guttmann A, Griffiths AM, et al. . Increasing incidence of paediatric inflammatory bowel disease in Ontario, Canada: evidence from health administrative data. Gut 2009;58:1490–7. 10.1136/gut.2009.188383
    1. Paramsothy S, Kamm MA, Kaakoush NO, et al. . Multidonor intensive faecal Microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet 2017;389:1218–28. 10.1016/S0140-6736(17)30182-4

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