Antimicrobial Therapy for Ulcerative Colitis (UC)

Summary

The Aim of this randoized controlled pilot study is to find a better treatment strategy for active UC based on the recent knowledge regarding the microbiota in UC and the beneficial or detrimental effects of antibiotics in restoring gut health and reducing inflammation. This study is designed to determine whether therapy with two antibiotics during a flare - amoxicillin and doxycillin, will be better than the current published antibiotic treatment combination using these antibiotics with metronidazole ( as the latter which may degrade beneficial species without adding benefit towards reducing pathobionts)

Timeline

Start

2019-07-25

Primary completion

2022-05-29

Completion

2022-05-30

Publications

• Background Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA, Essers J, Mitrovic M, Ning K, Cleynen I, Theatre E, Spain SL, Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L, Ananthakrishnan AN, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, Bitton A, Boucher G, Brand S, Buning C, Cohain A, Cichon S, D'Amato M, De Jong D, Devaney KL, Dubinsky M, Edwards C, Ellinghaus D, Ferguson LR, Franchimont D, Fransen K, Gearry R, Georges M, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, Hedl M, Hu X, Karlsen TH, Kupcinskas L, Kugathasan S, Latiano A, Laukens D, Lawrance IC, Lees CW, Louis E, Mahy G, Mansfield J, Morgan AR, Mowat C, Newman W, Palmieri O, Ponsioen CY, Potocnik U, Prescott NJ, Regueiro M, Rotter JI, Russell RK, Sanderson JD, Sans M, Satsangi J, Schreiber S, Simms LA, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, De Vos M, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhao H; International IBD Genetics Consortium (IIBDGC); Silverberg MS, Annese V, Hakonarson H, Brant SR, Radford-Smith G, Mathew CG, Rioux JD, Schadt EE, Daly MJ, Franke A, Parkes M, Vermeire S, Barrett JC, Cho JH. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012 Nov 1;491(7422):119-24. doi: 10.1038/nature11582.
• Background Manichanh C, Borruel N, Casellas F, Guarner F. The gut microbiota in IBD. Nat Rev Gastroenterol Hepatol. 2012 Oct;9(10):599-608. doi: 10.1038/nrgastro.2012.152. Epub 2012 Aug 21.
• Background Noor SO, Ridgway K, Scovell L, Kemsley EK, Lund EK, Jamieson C, Johnson IT, Narbad A. Ulcerative colitis and irritable bowel patients exhibit distinct abnormalities of the gut microbiota. BMC Gastroenterol. 2010 Nov 12;10:134. doi: 10.1186/1471-230X-10-134.
• Background Davenport M, Poles J, Leung JM, Wolff MJ, Abidi WM, Ullman T, Mayer L, Cho I, Loke P. Metabolic alterations to the mucosal microbiota in inflammatory bowel disease. Inflamm Bowel Dis. 2014 Apr;20(4):723-31. doi: 10.1097/MIB.0000000000000011.
• Background David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014 Jan 23;505(7484):559-63. doi: 10.1038/nature12820. Epub 2013 Dec 11.
• Background James SL, Christophersen CT, Bird AR, Conlon MA, Rosella O, Gibson PR, Muir JG. Abnormal fibre usage in UC in remission. Gut. 2015 Apr;64(4):562-70. doi: 10.1136/gutjnl-2014-307198. Epub 2014 Jul 18.
• Background Khalil NA, Walton GE, Gibson GR, Tuohy KM, Andrews SC. In vitro batch cultures of gut microbiota from healthy and ulcerative colitis (UC) subjects suggest that sulphate-reducing bacteria levels are raised in UC and by a protein-rich diet. Int J Food Sci Nutr. 2014 Feb;65(1):79-88. doi: 10.3109/09637486.2013.825700. Epub 2013 Aug 13.
• Background De Preter V, Arijs I, Windey K, Vanhove W, Vermeire S, Schuit F, Rutgeerts P, Verbeke K. Decreased mucosal sulfide detoxification is related to an impaired butyrate oxidation in ulcerative colitis. Inflamm Bowel Dis. 2012 Dec;18(12):2371-80. doi: 10.1002/ibd.22949. Epub 2012 Mar 20.
• Background Jowett SL, Seal CJ, Pearce MS, Phillips E, Gregory W, Barton JR, Welfare MR. Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study. Gut. 2004 Oct;53(10):1479-84. doi: 10.1136/gut.2003.024828.
• Background Pitcher MC, Beatty ER, Cummings JH. The contribution of sulphate reducing bacteria and 5-aminosalicylic acid to faecal sulphide in patients with ulcerative colitis. Gut. 2000 Jan;46(1):64-72. doi: 10.1136/gut.46.1.64.
• Background Ohkusa T, Nomura T, Terai T, Miwa H, Kobayashi O, Hojo M, Takei Y, Ogihara T, Hirai S, Okayasu I, Sato N. Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis: a randomized, controlled pilot trial with long-term follow-up. Scand J Gastroenterol. 2005 Nov;40(11):1334-42. doi: 10.1080/00365520510023648.
• Background Ohkusa T, Kato K, Terao S, Chiba T, Mabe K, Murakami K, Mizokami Y, Sugiyama T, Yanaka A, Takeuchi Y, Yamato S, Yokoyama T, Okayasu I, Watanabe S, Tajiri H, Sato N; Japan UC Antibiotic Therapy Study Group. Newly developed antibiotic combination therapy for ulcerative colitis: a double-blind placebo-controlled multicenter trial. Am J Gastroenterol. 2010 Aug;105(8):1820-9. doi: 10.1038/ajg.2010.84. Epub 2010 Mar 9.
• Background Turner D, Levine A, Kolho KL, Shaoul R, Ledder O. Combination of oral antibiotics may be effective in severe pediatric ulcerative colitis: a preliminary report. J Crohns Colitis. 2014 Nov;8(11):1464-70. doi: 10.1016/j.crohns.2014.05.010. Epub 2014 Jun 20.
• Background Terao S, Yamashiro K, Tamura I, Hirano T, Ohkusa T, Kato K. Antibiotic combination therapy for steroid withdrawal in steroid-dependent ulcerative colitis. Digestion. 2011;83(3):198-203. doi: 10.1159/000321811. Epub 2011 Jan 21.
• Background Kato K, Ohkusa T, Terao S, Chiba T, Murakami K, Yanaka A, Uehara T, Ishii Y, Soma M, Tajiri H. Adjunct antibiotic combination therapy for steroid-refractory or -dependent ulcerative colitis: an open-label multicentre study. Aliment Pharmacol Ther. 2014 May;39(9):949-56. doi: 10.1111/apt.12688. Epub 2014 Mar 13.
• Background Knoop KA, McDonald KG, Kulkarni DH, Newberry RD. Antibiotics promote inflammation through the translocation of native commensal colonic bacteria. Gut. 2016 Jul;65(7):1100-9. doi: 10.1136/gutjnl-2014-309059. Epub 2015 Jun 4.

Drugs

Indications