Skip to main content

Advertisement

SpringerLink
Log in

New and Investigational Agents for Irritable Bowel Syndrome

  • Large Intestine (B Cash, Section Editor)
  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Irritable bowel syndrome (IBS) affects about 15 % of the US population and results in significant morbidity and health care costs. There remains a significant unmet need for effective treatments particularly for the pain component of IBS and other functional gastrointestinal disorders (FGIDs). Progress made in our understanding of pathophysiological mechanisms such as the role of altered bile acid metabolism, neurohormonal regulation, immune dysfunction, the epithelial barrier and secretory properties of the gut has led to advancements in therapeutic armamentarium for IBS. This review discusses the new drugs for constipation and diarrhea-predominant IBS subtypes that have been tested or have been under investigation over the last 3–4 years. Overall, there is a promising pipeline of investigational drugs for the future treatment of IBS and related FGIDs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Leong SA, Barghout V, Birnbaum HG, Thibeault CE, Ben-Hamadi R, Frech F, et al. The economic consequences of irritable bowel syndrome: a US employer perspective. Arch Intern Med. 2003;163(8):929–35. doi:10.1001/archinte.163.8.929.

    Article  PubMed  Google Scholar 

  2. Camilleri M. Peripheral mechanisms in irritable bowel syndrome. N Engl J Med. 2013;368(6):578–9. doi:10.1056/NEJMc1214185. Key review article outlining peripheral pathophysiological mechanisms for IBS providing insights into treatment targets.

    PubMed  CAS  Google Scholar 

  3. Dupont HL. Review article: evidence for the role of gut microbiota in irritable bowel syndrome and its potential influence on therapeutic targets. Aliment Pharmacol Ther. 2014;39(10):1033–42. doi:10.1111/apt.12728.

    Article  PubMed  CAS  Google Scholar 

  4. Spiller R, Garsed K. Postinfectious irritable bowel syndrome. Gastroenterology. 2009;136(6):1979–88. doi:10.1053/j.gastro.2009.02.074.

    Article  PubMed  Google Scholar 

  5. Matricon J, Meleine M, Gelot A, Piche T, Dapoigny M, Muller E, et al. Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome. Aliment Pharmacol Ther. 2012;36(11-12):1009–31. doi:10.1111/Apt.12080.

    Article  PubMed  CAS  Google Scholar 

  6. Wong BS, Camilleri M, Carlson P, McKinzie S, Busciglio I, Bondar O, et al. Increased bile acid biosynthesis is associated with irritable bowel syndrome with diarrhea. Clin Gastroenterol H. 2012;10(9):1009–15. doi:10.1016/j.cgh.2012.05.006.

    Article  CAS  Google Scholar 

  7. Shin A, Camilleri M, Vijayvargiya P, Busciglio I, Burton D, Ryks M, et al. Bowel functions, fecal unconjugated primary and secondary bile acids, and colonic transit in patients with irritable bowel syndrome. Clin Gastroenterol H. 2013;11(10):1270–75. doi:10.1016/j.cgh.2013.04.020.

    Article  CAS  Google Scholar 

  8. Busby RW, Bryant AP, Bartolini WP, Cordero EA, Hannig G, Kessler MM, et al. Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit. Eur J Pharmacol. 2010;649(1-3):328–35. doi:10.1016/j.ejphar.2010.09.019.

    Article  PubMed  CAS  Google Scholar 

  9. Castro J, Harrington AM, Hughes PA, Martin CM, Ge P, Shea CM, et al. Linaclotide inhibits colonic nociceptors and relieves abdominal pain via guanylate cyclase-C and extracellular cyclic guanosine 3',5'-monophosphate. Gastroenterology. 2013;145(6):1334–46. doi:10.1053/j.gastro.2013.08.017.

    Article  PubMed  CAS  Google Scholar 

  10. Rao S, Lembo AJ, Shiff SJ, Lavins BJ, Currie MG, Jia XD, et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol. 2012;107(11):1714–24. doi:10.1038/ajg.2012.255.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Rao SS, Quigley EM, Shiff SJ, Lavins BJ, Kurtz CB, MacDougall JE, et al. Effect of linaclotide on severe abdominal symptoms in patients with irritable bowel syndrome with constipation. Clin Gastroenterol Hepatol. 2014;12(4):616–23. doi:10.1016/j.cgh.2013.09.022.

    Article  PubMed  CAS  Google Scholar 

  12. Videlock EJ, Cheng V, Cremonini F. Effects of linaclotide in patients with irritable bowel syndrome with constipation or chronic constipation: a meta-analysis. Clin Gastroenterol Hepatol. 2013;11(9):1084–92. doi:10.1016/j.cgh.2013.04.032. Important meta-analysis of treatment efficacy of linaclotide for management of IBS-C or chronic constipation.

    Article  PubMed  CAS  Google Scholar 

  13. Chey WD, Lembo AJ, Lavins BJ, Shiff SJ, Kurtz CB, Currie MG, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol. 2012;107(11):1702–12. doi:10.1038/Ajg.2012.254.

    Article  PubMed  CAS  Google Scholar 

  14. Shailubhai K, Comiskey S, Foss JA, Feng R, Barrow L, Comer GM, et al. Plecanatide, an oral guanylate cyclase C agonist acting locally in the gastrointestinal tract, is safe and well-tolerated in single doses. Dig Dis Sci. 2013;58(9):2580–6. doi:10.1007/s10620-013-2684-z.

    Article  PubMed  CAS  Google Scholar 

  15. Miner PB, Surowitz R, Fogel R, Koltun W, Drossman DA, Camilleri M, et al. Plecanatide, a novel guanylate cyclase-C (GC-C) receptor agonist, is efficacious and safe in patients with chronic idiopathic constipation (CIC): results from a 951 patient, 12 week, multi-center trial. Gastroenterology. 2013;144(5):S163-S. Large clinical trial of plecanatide.

    Article  Google Scholar 

  16. Jadav AM, Mcmullin CM, Smith J, Chapple K, Brown SR. The association between prucalopride efficacy and constipation type. Tech Coloproctol. 2013;17(5):555–9. doi:10.1007/s10151-013-1017-8.

    Article  PubMed  CAS  Google Scholar 

  17. Shin A, Camilleri M, Kolar G, Erwin P, West CP, Murad MH. Systematic review with meta-analysis: highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) in chronic constipation. Aliment Pharmacol Ther. 2014;39(3):239–53. doi:10.1111/apt.12571.

    Article  PubMed  CAS  Google Scholar 

  18. Piessevaux H, Corazziari E, Rey E, Simren M, Wiechowska-Kozlowska A, Kerstens R, et al. A randomized, double-blind, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of long-term treatment with prucalopride. Neurogastroenterol Motil. 2015;27:805–15. doi:10.1111/nmo.12553.

    Article  PubMed  CAS  Google Scholar 

  19. Shin A, Acosta A, Camilleri M, Boldingh A, Burton D, Ryks M, et al. A randomized trial of 5-hydroxytryptamine4-receptor agonist, YKP10811, on colonic transit and bowel function in functional constipation. Clin Gastroenterol Hepatol. 2015;13(4):701–8. doi:10.1016/j.cgh.2014.08.012. e1.

    Article  PubMed  CAS  Google Scholar 

  20. Scarpellini E, Tack J. Renzapride: a new drug for the treatment of constipation in the irritable bowel syndrome. Expert Opin Investig Drugs. 2008;17(11):1663–70. doi:10.1517/13543784.17.11.1663.

    Article  PubMed  CAS  Google Scholar 

  21. Lembo AJ, Cremonini F, Meyers N, Hickling R. Clinical trial: renzapride treatment of women with irritable bowel syndrome and constipation—a double-blind, randomized, placebo-controlled, study. Aliment Pharmacol Ther. 2010;31(9):979–90. doi:10.1111/j.1365-2036.2010.04265.x.

    PubMed  CAS  Google Scholar 

  22. Mozaffari S, Nikfar S, Abdollahi M. Efficacy and tolerability of renzapride in irritable bowel syndrome: a meta-analysis of randomized, controlled clinical trials including 2528 patients. Arch Med Sci. 2014;10(1):10–8. doi:10.5114/aoms.2014.40729.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  23. Camilleri M, Murphy R, Chadwick VS. Dose-related effects of chenodeoxycholic acid in the rabbit colon. Dig Dis Sci. 1980;25(6):433–8.

    Article  PubMed  CAS  Google Scholar 

  24. Mekjian HS, Phillips SF, Hofmann AF. Colonic secretion of water and electrolytes induced by bile acids: perfusion studies in man. J Clin Invest. 1971;50(8):1569–77. doi:10.1172/JCI106644.

    Article  PubMed  CAS  Google Scholar 

  25. Kirwan WO, Smith AN, Mitchell WD, Falconer JD, Eastwood MA. Bile acids and colonic motility in the rabbit and the human. Gut. 1975;16(11):894–902.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Rao AS, Wong BS, Camilleri M, Odunsi-Shiyanbade ST, McKinzie S, Ryks M, et al. Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis. Gastroenterology. 2010;139(5):1549. doi:10.1053/j.gastro.2010.07.052. Important proof of principle study suggestion important of bile acid modulation in management of functional GI disorders.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Wong BS, Camilleri M, McKinzie S, Burton D, Graffner H, Zinsmeister AR. Effects of A3309, an ileal bile acid transporter inhibitor, on colonic transit and symptoms in females with functional constipation. Am J Gastroenterol. 2011;106(12):2154–64. doi:10.1038/ajg.2011.285.

    Article  PubMed  CAS  Google Scholar 

  28. Chey WD, Camilleri M, Chang L, Rikner L, Graffner H. A randomized placebo-controlled phase IIb trial of A3309, a bile acid transporter inhibitor, for chronic idiopathic constipation. Am J Gastroenterol. 2011;106(10):1803–12. doi:10.1038/Ajg.2011.162.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Fukudo S, Hongo M, Kaneko H, Takano M, Ueno R. Lubiprostone increases spontaneous bowel movement frequency and quality of life in patients with chronic idiopathic constipation. Clin Gastroenterol H. 2015;13(2):294–U121. doi:10.1016/j.cgh.2014.08.026.

    Article  CAS  Google Scholar 

  30. A randomized, double-blind, placebo-controlled study to assess the safety and efficacy of AZD1722 for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) [database on the Internet]. clinicaltrials.gov. Available from: https://clinicaltrials.gov/ct2/show/NCT01923428?term=NCT01923428&rank=1. Accessed: 17th april 2015

  31. Trinkley KE, Nahata MC. Medication management of irritable bowel syndrome. Digestion. 2014;89(4):253–67. doi:10.1159/000362405.

    Article  PubMed  CAS  Google Scholar 

  32. Clinical study on the effect of Neu-P11 on symptoms in patients with diarrhea-irritable bowel syndrome (D-IBS) [database on the Internet]. clinicaltrials.gov. Available from: https://clinicaltrials.gov/ct2/show/NCT01558284?term=NCT01558284&rank=1. Accessed: 17th april 2015

  33. Goldberg M, Li YP, Johanson JF, Mangel AW, Kitt M, Beattie DT, et al. Clinical trial: the efficacy and tolerability of velusetrag, a selective 5-HT4 agonist with high intrinsic activity, in chronic idiopathic constipation—a 4-week, randomized, double-blind, placebo-controlled, dose-response study. Aliment Pharmacol Ther. 2010;32(9):1102–12. doi:10.1111/j.1365-2036.2010.04456.x.

    Article  PubMed  CAS  Google Scholar 

  34. Palme M, Milner PG, Ellis DJ, Marmon T, Canafax DM. 905 A novel gastrointestinal prokinetic, ATI-7505, increased spontaneous bowel movements (Sbms) in a phase II, randomized, placebo-controlled study of patients with chronic idiopathic constipation (CIC). Gastroenterology. 2010;138(5):S-128–S-9. doi:10.1016/s0016-5085(10)60590-2.

    Article  Google Scholar 

  35. Lee KJ, Kim NY, Kwon JK, Huh KC, Lee OY, Lee JS et al. Efficacy of ramosetron in the treatment of male patients with irritable bowel syndrome with diarrhea: a multicenter, randomized clinical trial, compared with mebeverine. Neurogastroent Motil. 2011;23(12):1098-E540. doi:DOI 10.1111/j.1365-2982.2011.01771.x.

  36. Fukudo S, Ida M, Akiho H, Nakashima Y, Matsuedak K. Effect of ramosetron on stool consistency in male patients with irritable bowel syndrome with diarrhea. Clin Gastroenterol H. 2014;12(6):953. doi:10.1016/j.cgh.2013.11.024. Important clinical trial showing efficacy and lack of significant side effects with Ramosetron which holds promise for IBS-D.

    Article  CAS  Google Scholar 

  37. Chiba T, Yamamoto K, Sato S, Suzuki K. Long-term efficacy and safety of ramosetron in the treatment of diarrhea-predominant irritable bowel syndrome. Clin Exp Gastroenterol. 2013;6:123–8. doi:10.2147/CEG.S32721.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  38. Prometheus, laboratories. Highlights of prescribing information. FDA. 2008. http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021107s013lbl.pdf.

  39. Freiman JJJ, Frazier KS, Yang QM, Liu Q, Brown P. LX1031: Inhibition of 5-HT synthesis as a new target in the management of irritable bowel syndrome (IBS). Neurogastroenterology Motility. 2009;21.

  40. Brown PM, Drossman DA, Wood AJJ, Cline GA, Frazier KS, Jackson JI, et al. The tryptophan hydroxylase inhibitor LX1031 shows clinical benefit in patients with nonconstipating irritable bowel syndrome. Gastroenterology. 2011;141(2):507–16. doi:10.1053/j.gastro.2011.05.005.

    Article  PubMed  CAS  Google Scholar 

  41. Nakamura A, Tanaka T, Imanishi A, Kawamoto M, Toyoda M, Mizojiri G, et al. Bidirectional regulation of human colonic smooth muscle contractility by tachykinin NK(2) receptors. J Pharmacol Sci. 2011;117(2):106–15.

    Article  PubMed  CAS  Google Scholar 

  42. Tack JF e. Efficacy of ibodutant, a selective antagonist of neurokinin 2 receptors, in irritable bowel syndrome with diarrhea (IBS-D): the results of a double-blind, randomized, placebo-controlled, parallel-group phase II study. Gastroenterology. 2013;144(5 supple 1):S92–S3. doi:10.1016/S0016-5085(13)60340-6. Results are encouraging and phase III study is already in process.

    Article  Google Scholar 

  43. 52-Week efficacy and safety study of ibodutant in women with irritable bowel syndrome with diarrhea [database on the Internet]. clinicaltrials.gov. Available from: https://clinicaltrials.gov/ct2/show/NCT02120027?term=ibodutant+ibs&rank=2. Accessed: 17th april 2015 Press release for recent drugs approved for IBS-D by the FDA.

  44. Dove LS, Lembo A, Randall CW, Fogel R, Andrae D, Davenport JM et al. Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology. 2013;145(2):329-38 e1. doi:10.1053/j.gastro.2013.04.006. Eluxadoline has been recently approved by the FDA for treatment of IBS-D.

  45. FDA. FDA approves two therapies to treat IBS D. FDA.gov. 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm448328.htm.

  46. Mangel AW, Bornstein JD, Hamm LR, Buda J, Wang J, Irish W, et al. Clinical trial: asimadoline in the treatment of patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2008;28(2):239–49. doi:10.1111/j.1365-2036.2008.03730.x.

    Article  PubMed  CAS  Google Scholar 

  47. Study of asimadoline to treat diarrhea-predominant irritable bowel syndrome (D-IBS) [database on the Internet]. clinicaltrials.gov. Available from: https://clinicaltrials.gov/ct2/show/NCT01100684?term=asimadoline&rank=4. Accessed: 17th April 2015.

  48. Tack JF, Miner Jr PB, Fischer L, Harris MS. Randomised clinical trial: the safety and efficacy of AST-120 in non-constipating irritable bowel syndrome—a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2011;34(8):868–77. doi:10.1111/j.1365-2036.2011.04818.x.

    Article  PubMed  CAS  Google Scholar 

  49. Wedlake L, A'Hern R, Russell D, Thomas K, Walters JRF, Andreyev HJN. Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2009;30(7):707–17. doi:10.1111/j.1365-2036.2009.04081.x.

    Article  PubMed  CAS  Google Scholar 

  50. Odunsi-Shiyanbade ST, Camilleri M, McKinzie S, Burton D, Carlson P, Busciglio IA, et al. Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam, on intestinal transit and bowel function. Clin Gastroenterol Hepatol. 2010;8(2):159–65. doi:10.1016/j.cgh.2009.10.020.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  51. Camilleri M, Acosta A, Busciglio I, Boldingh A, Dyer RB, Zinsmeister AR, et al. Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2015;41(5):438–48. doi:10.1111/Apt.13065. Important trial for modulation of bile acid pathway in management of IBS-D.

    Article  PubMed  CAS  Google Scholar 

  52. Pellicciari R, Costantino G, Camaioni E, Sadeghpour BM, Entrena A, Willson TM, et al. Bile acid derivatives as ligands of the farnesoid X receptor. Synthesis, evaluation, and structure-activity relationship of a series of body and side chain modified analogues of chenodeoxycholic acid. J Med Chem. 2004;47(18):4559–69. doi:10.1021/jm049904b.

    Article  PubMed  CAS  Google Scholar 

  53. Walters JR, Johnston IM, Nolan JD, Vassie C, Pruzanski ME, Shapiro DA. The response of patients with bile acid diarrhoea to the farnesoid X receptor agonist obeticholic acid. Aliment Pharmacol Ther. 2015;41(1):54–64. doi:10.1111/apt.12999. Promising Farnesoid X agonist for management of bile acid diarrhea.

    Article  PubMed  CAS  Google Scholar 

  54. Bajor A, Tornblom H, Rudling M, Ung KA, Simren M. Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS. Gut. 2015;64(1):84–92. doi:10.1136/gutjnl-2013-305965.

    Article  PubMed  CAS  Google Scholar 

  55. Clave P, Acalovschi M, Triantafillidis JK, Uspensky YP, Kalayci C, Shee V, et al. Randomised clinical trial: otilonium bromide improves frequency of abdominal pain, severity of distention and time to relapse in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2011;34(4):432–42. doi:10.1111/j.1365-2036.2011.04730.x.

    Article  PubMed  CAS  Google Scholar 

  56. Chmielewska-Wilkon D, Reggiardo G, Egan CG. Otilonium bromide in irritable bowel syndrome: a dose-ranging randomized double-blind placebo-controlled trial. World J Gastroenterol. 2014;20(34):12283–91. doi:10.3748/wjg.v20.i34.12283.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  57. Fukushima Y, Suzuki H, Matsuzaki J, Kiyosue A, Hibi T. Efficacy of solifenacin on irritable bowel syndrome with diarrhea: open-label prospective pilot trial. J Neurogastroenterol. 2012;18(3):317–23. doi:10.5056/jnm.2012.18.3.317.

    Article  Google Scholar 

  58. Zhou QQ, Souba WW, Croce CM, Verne GN. MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome. Gut. 2010;59(6):775–84. doi:10.1136/gut.2009.181834.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  59. Basra SVG, Zhou Q. Randomized placebo controlled trial of glutamine for the treatment of diarrhea-predominant irritable bowel syndrome. Gastroenterology. 2013;144(5 suppl 1):S160.

    Article  Google Scholar 

  60. Bertrand J, Ghouzali I, Guerin C, Bole-Feysot C, Gouteux M, Dechelotte P, et al. Glutamine restores tight junction protein claudin-1 expression in colonic mucosa of patients with diarrhea-predominant irritable bowel syndrome. JPEN J Parenter Enteral Nutr. 2015. doi:10.1177/0148607115587330.

    PubMed  Google Scholar 

  61. Takayanagi I, Hisayama T, Iwase M, Sakuma N, Nagai H. Pharmacological properties of tiropramide, an antispasmodic drug. Gen Pharmacol. 1989;20(3):335–9.

    Article  PubMed  CAS  Google Scholar 

  62. Uruno T, Shirane M, Wada K, Tsunematsu R, Nagahamaya K, Matsuoka Y, et al. Possible mechanisms of action of the antispasmodic agent tiropramide in the isolated detrusor from rats. Jpn J Pharmacol. 1992;60(3):275–80.

    Article  PubMed  CAS  Google Scholar 

  63. Lee KN, Lee OY, Choi MG, Sohn CI, Huh KC, Park KS, et al. Efficacy and safety of tiropramide in the treatment of patients with irritable bowel syndrome: a multicenter, randomized, double-blind, non-inferiority trial compared with octylonium. J Neurogastroenterol. 2014;20(1):113–21. doi:10.5056/jnm.2014.20.1.113.

    Article  Google Scholar 

  64. Strege PR, Evangelista S, Lyford GL, Sarr MG, Farrugia G. Otilonium bromide inhibits calcium entry through L-type calcium channels in human intestinal smooth muscle. Neurogastroenterol Motil. 2004;16(2):167–73. doi:10.1111/j.1365-2982.2004.00517.x.

    Article  PubMed  CAS  Google Scholar 

  65. Gallego D, Auli M, Aleu J, Martinez E, Rofes L, Marti-Rague J, et al. Effect of otilonium bromide on contractile patterns in the human sigmoid colon. Neurogastroenterol Motil. 2010;22(6):e180–91. doi:10.1111/j.1365-2982.2010.01495.x.

    Article  PubMed  CAS  Google Scholar 

  66. Alam MS, Roy PK, Miah AR, Mollick SH, Khan MR, Mahmud MC, et al. Efficacy of peppermint oil in diarrhea predominant IBS—a double blind randomized placebo - controlled study. Mymensingh Med J. 2013;22(1):27–30.

    PubMed  CAS  Google Scholar 

  67. Comparing a 182mg colon-targeted-delivery peppermint oil capsule (Tempocol-ColoPulse®) and a 182mg enteric-coated peppermint oil capsule (Tempocol®), a Pharmacokinetic Study [database on the Internet]. clinicaltrials.gov. Available from: https://clinicaltrials.gov/ct2/show/NCT02291445?term=peppermint+oil+ibs&rank=1. Accessed: 17th april 2015.

  68. A phase 2, randomized, double-blind, placebo-controlled pilot study to assess the efficacy, safety and tolerability, of ASP7147 in patients with diarrhea predominant irritable bowel syndrome (IBS-D) [database on the Internet]. clinicaltrials.gov. Available from: https://clinicaltrials.gov/ct2/show/NCT01896583?term=NCT01896583&rank=1. Accessed.

  69. Pimentel M, Chow EJ, Lin HC. Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. a double-blind, randomized, placebo-controlled study. Am J Gastroenterol. 2003;98(2):412–9. doi:10.1111/j.1572-0241.2003.07234.x.

    PubMed  Google Scholar 

  70. Yu D, Cheeseman F, Vanner S. Combined oro-caecal scintigraphy and lactulose hydrogen breath testing demonstrate that breath testing detects oro-caecal transit, not small intestinal bacterial overgrowth in patients with IBS. Gut. 2011;60(3):334–40. doi:10.1136/gut.2009.205476.

    Article  PubMed  Google Scholar 

  71. Paula H, Grover M, Halder SL, Locke 3rd GR, Schleck CD, Zinsmeister AR, et al. Non-enteric infections, antibiotic use, and risk of development of functional gastrointestinal disorders. Neurogastroenterol Motil. 2015. doi:10.1111/nmo.12655.

    PubMed  Google Scholar 

  72. Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364(1):22–32. doi:10.1056/Nejmoa1004409. Results instrumental in leading to recent approval of Rifaximin by the FDA.

    Article  PubMed  CAS  Google Scholar 

  73. Pimentel M, Chang C, Chua KS, Mirocha J, DiBaise J, Rao S, et al. Antibiotic treatment of constipation-predominant irritable bowel syndrome. Dig Dis Sci. 2014;59(6):1278–85. doi:10.1007/s10620-014-3157-8.

    Article  PubMed  CAS  Google Scholar 

  74. Corinaldesi R, Stanghellini V, Cremon C, Gargano L, Cogliandro RF, De Giorgio R, et al. Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof-of-concept study. Aliment Pharmacol Ther. 2009;30(3):245–52. doi:10.1111/j.1365-2036.2009.04041.x.

    Article  PubMed  CAS  Google Scholar 

  75. Barbara G, Cremon C, Annese V, Basilisco G, Bazzoli F, Bellini M, et al. Randomised controlled trial of mesalazine in IBS. Gut. 2014. doi:10.1136/gutjnl-2014-308188.

    Google Scholar 

  76. Lam C, Tan W, Leighton M, Hastings M, Lingaya M, Falcone Y, et al. A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D). Gut. 2015. doi:10.1136/gutjnl-2015-309122.

    Google Scholar 

  77. Klooker TK, Braak B, Koopman KE, Welting O, Wouters MM, van der Heide S, et al. The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome. Gut. 2010;59(9):1213–21. doi:10.1136/gut.2010.213108.

    Article  PubMed  CAS  Google Scholar 

  78. van Wanrooij SWM, Van Oudenhove L, Vermeire S, Rutgeerts PJ, Boeckxstaens GE. Effect of the H1-receptor antagonist ebastin on visceral perception and clinical symptoms in IBS. Gastroenterology. 2013;144(5 supple 1):S160.

    Article  Google Scholar 

  79. IBS treatment with H1-receptor antagonists [database on the Internet]. clinicaltrials.gov. 2012. Available from: https://clinicaltrials.gov/ct2/show/record/NCT01144832?term=ebastine+ibs&rank=2. Accessed: 2nd june 2015.

  80. Peripheral histamine 1 receptor blockade in IBS [database on the Internet]. clinicaltrials.gov. 2015. Available from: https://clinicaltrials.gov/ct2/show/NCT01908465?term=ebastine+ibs&rank=1. Accessed: 2nd june 2015.

  81. Hellstrom PM, Hein J, Bytzer P, Bjornsson E, Kristensen J, Schambye H. Clinical trial: the glucagon-like peptide-1 analogue ROSE-010 for management of acute pain in patients with irritable bowel syndrome: a randomized, placebo-controlled, double-blind study. Aliment Pharmacol Ther. 2009;29(2):198–206. doi:10.1111/j.1365-2036.2008.03870.x.

    Article  PubMed  CAS  Google Scholar 

  82. Hellstrom PM, Naslund E, Edholm T, Schmidt PT, Kristensen J, Theodorsson E, et al. GLP-1 suppresses gastrointestinal motility and inhibits the migrating motor complex in healthy subjects and patients with irritable bowel syndrome. Neurogastroent Motil. 2008;20(6):649–59. doi:10.1111/j.1365-2982.2007.01079.x.

    Article  CAS  Google Scholar 

  83. Camilleri M, Vazquez-Roque M, Iturrino J, Boldingh A, Burton D, McKinzie S, et al. Effect of a glucagon-like peptide 1 analog, ROSE-010, on GI motor functions in female patients with constipation-predominant irritable bowel syndrome. Am J Physiol-Gastr L. 2012;303(1):G120–G8. doi:10.1152/ajpgi.00076.2012.

    CAS  Google Scholar 

  84. A double-blind, randomised, placebo-controlled study on the efficacy of iberogast (STW 5) in patients with irritable bowel syndrome [database on the Internet]. clinicaltrials.gov. 2015. Available from: https://clinicaltrials.gov/ct2/show/NCT01940848?term=iberogast&rank=1. Accessed: 17th April 2015.

  85. Effect of daikenchuto (TU 100), a gastrointestinal nerve modulator, on rectal sensation in patients with irritable bowel syndrome [database on the Internet]. clinicaltirals.gov. Available from: https://clinicaltrials.gov/ct2/show/NCT01890837?term=NCT01890837&rank=1. Accessed: 17th april 2015.

  86. Nielsen LM, Olesen AE, Andresen T, Simren M, Tornblom H, Drewes AM. Efficacy and safety of PPC-5650 on experimental rectal pain in patients with irritable bowel syndrome. Basic Clin Pharmacol Toxicol. 2015;116(2):140–5. doi:10.1111/bcpt.12294.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Akhilesh Wadhwa

  2. Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Michael Camilleri & Madhusudan Grover

Authors
  1. Akhilesh Wadhwa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Camilleri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Madhusudan Grover
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Michael Camilleri or Madhusudan Grover.

Ethics declarations

Conflict of Interest

Akhilesh Wadhwa declares that he has no conflict of interest; Michael Camilleri reports grants from SmithKline, grants from Albireo, during the conduct of the study; Madhusudan Grover reports grants from Takeda, Dong-A and NIDDK K23 DK 103911 during the conduct of the study.

Human and Animal Rights and Informed Consent

This article does not contain any studies with animal subjects performed by any of the authors. With regard to the authors’ research cited in this paper, all procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000 and 2008.

Additional information

This article is part of the Topical Collection on Large Intestine

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wadhwa, A., Camilleri, M. & Grover, M. New and Investigational Agents for Irritable Bowel Syndrome. Curr Gastroenterol Rep 17, 46 (2015). https://doi.org/10.1007/s11894-015-0473-x

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11894-015-0473-x

Keywords

Search

Navigation