The Role of Irritable Bowel Syndrome in Lactose Intolerance (LION)

Summary

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease. There is no well-defined pharmacological treatment. This clinical trial is a prospective, double-blind, two-armed randomized controlled, single-center trial. It is created to examine the role of IBS in patients with lactose intolerance. IBS patients undergo lactose H2 breath test (LHBT) and lactose tolerance test (LTT). Those with positive LTT and LHBT will be randomized into two groups: alverine-citrate + simethicone and lactase group (1) or alverin-citrate + simethicone with the placebo group (2). The goal of this study is to compare the lactase enzyme with placebo in IBS patients with lactose intolerance.

Timeline

Start

2022-09

Primary completion

2026-09

Completion

2026-12

Publications

• Background Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006 Apr;130(5):1480-91. doi: 10.1053/j.gastro.2005.11.061.
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• Background Muller-Lissner SA, Bollani S, Brummer RJ, Coremans G, Dapoigny M, Marshall JK, Muris JW, Oberndorff-Klein Wolthuis A, Pace F, Rodrigo L, Stockbrugger R, Vatn MH. Epidemiological aspects of irritable bowel syndrome in Europe and North America. Digestion. 2001;64(3):200-4. doi: 10.1159/000048862.
• Background Drossman DA, Morris CB, Schneck S, Hu YJ, Norton NJ, Norton WF, Weinland SR, Dalton C, Leserman J, Bangdiwala SI. International survey of patients with IBS: symptom features and their severity, health status, treatments, and risk taking to achieve clinical benefit. J Clin Gastroenterol. 2009 Jul;43(6):541-50. doi: 10.1097/MCG.0b013e318189a7f9.
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• Background Simren M, Svedlund J, Posserud I, Bjornsson ES, Abrahamsson H. Health-related quality of life in patients attending a gastroenterology outpatient clinic: functional disorders versus organic diseases. Clin Gastroenterol Hepatol. 2006 Feb;4(2):187-95. doi: 10.1016/s1542-3565(05)00981-x.
• Background Bohn L, Storsrud S, Liljebo T, Collin L, Lindfors P, Tornblom H, Simren M. Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: a randomized controlled trial. Gastroenterology. 2015 Nov;149(6):1399-1407.e2. doi: 10.1053/j.gastro.2015.07.054. Epub 2015 Aug 5.
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• Background Simren M, Barbara G, Flint HJ, Spiegel BM, Spiller RC, Vanner S, Verdu EF, Whorwell PJ, Zoetendal EG; Rome Foundation Committee. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut. 2013 Jan;62(1):159-76. doi: 10.1136/gutjnl-2012-302167. Epub 2012 Jun 22.
• Background Miller V, Hopkins L, Whorwell PJ. Suicidal ideation in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol. 2004 Dec;2(12):1064-8. doi: 10.1016/s1542-3565(04)00545-2.
• Background Yang J, Fox M, Cong Y, Chu H, Zheng X, Long Y, Fried M, Dai N. Lactose intolerance in irritable bowel syndrome patients with diarrhoea: the roles of anxiety, activation of the innate mucosal immune system and visceral sensitivity. Aliment Pharmacol Ther. 2014 Feb;39(3):302-11. doi: 10.1111/apt.12582. Epub 2013 Dec 5.
• Background Lomer MC, Parkes GC, Sanderson JD. Review article: lactose intolerance in clinical practice--myths and realities. Aliment Pharmacol Ther. 2008 Jan 15;27(2):93-103. doi: 10.1111/j.1365-2036.2007.03557.x. Epub 2007 Oct 23.
• Background Suchy FJ, Brannon PM, Carpenter TO, Fernandez JR, Gilsanz V, Gould JB, Hall K, Hui SL, Lupton J, Mennella J, Miller NJ, Osganian SK, Sellmeyer DE, Wolf MA. National Institutes of Health Consensus Development Conference: lactose intolerance and health. Ann Intern Med. 2010 Jun 15;152(12):792-6. doi: 10.7326/0003-4819-152-12-201006150-00248. Epub 2010 Apr 19. No abstract available.
• Background Misselwitz B, Pohl D, Fruhauf H, Fried M, Vavricka SR, Fox M. Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment. United European Gastroenterol J. 2013 Jun;1(3):151-9. doi: 10.1177/2050640613484463.
• Background Monsbakken KW, Vandvik PO, Farup PG. Perceived food intolerance in subjects with irritable bowel syndrome-- etiology, prevalence and consequences. Eur J Clin Nutr. 2006 May;60(5):667-72. doi: 10.1038/sj.ejcn.1602367.
• Background Di Stefano M, Miceli E, Mazzocchi S, Tana P, Moroni F, Corazza GR. Visceral hypersensitivity and intolerance symptoms in lactose malabsorption. Neurogastroenterol Motil. 2007 Nov;19(11):887-95. doi: 10.1111/j.1365-2982.2007.00973.x. Epub 2007 Aug 17.
• Background Zhu Y, Zheng X, Cong Y, Chu H, Fried M, Dai N, Fox M. Bloating and distention in irritable bowel syndrome: the role of gas production and visceral sensation after lactose ingestion in a population with lactase deficiency. Am J Gastroenterol. 2013 Sep;108(9):1516-25. doi: 10.1038/ajg.2013.198. Epub 2013 Aug 6.
• Background Vesa TH, Seppo LM, Marteau PR, Sahi T, Korpela R. Role of irritable bowel syndrome in subjective lactose intolerance. Am J Clin Nutr. 1998 Apr;67(4):710-5. doi: 10.1093/ajcn/67.4.710.
• Background Vernia P, Di Camillo M, Marinaro V. Lactose malabsorption, irritable bowel syndrome and self-reported milk intolerance. Dig Liver Dis. 2001 Apr;33(3):234-9. doi: 10.1016/s1590-8658(01)80713-1.
• Background Varju P, Gede N, Szakacs Z, Hegyi P, Cazacu IM, Pecsi D, Fabian A, Szepes Z, Vincze A, Tenk J, Balasko M, Rumbus Z, Garami A, Csupor D, Czimmer J. Lactose intolerance but not lactose maldigestion is more frequent in patients with irritable bowel syndrome than in healthy controls: A meta-analysis. Neurogastroenterol Motil. 2019 May;31(5):e13527. doi: 10.1111/nmo.13527. Epub 2018 Dec 17.
• Background Yang J, Deng Y, Chu H, Cong Y, Zhao J, Pohl D, Misselwitz B, Fried M, Dai N, Fox M. Prevalence and presentation of lactose intolerance and effects on dairy product intake in healthy subjects and patients with irritable bowel syndrome. Clin Gastroenterol Hepatol. 2013 Mar;11(3):262-268.e1. doi: 10.1016/j.cgh.2012.11.034. Epub 2012 Dec 13.
• Background Bohmer CJ, Tuynman HA. The clinical relevance of lactose malabsorption in irritable bowel syndrome. Eur J Gastroenterol Hepatol. 1996 Oct;8(10):1013-6. doi: 10.1097/00042737-199610000-00015.
• Background Vernia P, Ricciardi MR, Frandina C, Bilotta T, Frieri G. Lactose malabsorption and irritable bowel syndrome. Effect of a long-term lactose-free diet. Ital J Gastroenterol. 1995 Apr;27(3):117-21.
• Background Lisker R, Solomons NW, Perez Briceno R, Ramirez Mata M. Lactase and placebo in the management of the irritable bowel syndrome: a double-blind, cross-over study. Am J Gastroenterol. 1989 Jul;84(7):756-62.
• Background Hillila M, Farkkila MA, Sipponen T, Rajala J, Koskenpato J. Does oral alpha-galactosidase relieve irritable bowel symptoms? Scand J Gastroenterol. 2016 Jan;51(1):16-21. doi: 10.3109/00365521.2015.1063156. Epub 2015 Jul 2.
• Background Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K, Hrobjartsson A, Mann H, Dickersin K, Berlin JA, Dore CJ, Parulekar WR, Summerskill WS, Groves T, Schulz KF, Sox HC, Rockhold FW, Rennie D, Moher D. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013 Feb 5;158(3):200-7. doi: 10.7326/0003-4819-158-3-201302050-00583.
• Background Hayase M, Hashitani H, Suzuki H, Kohri K, Brading AF. Evolving mechanisms of action of alverine citrate on phasic smooth muscles. Br J Pharmacol. 2007 Dec;152(8):1228-38. doi: 10.1038/sj.bjp.0707496. Epub 2007 Oct 15.
• Background Ducrotte P, Grimaud JC, Dapoigny M, Personnic S, O'Mahony V, Andro-Delestrain MC. On-demand treatment with alverine citrate/simeticone compared with standard treatments for irritable bowel syndrome: results of a randomised pragmatic study. Int J Clin Pract. 2014 Feb;68(2):245-54. doi: 10.1111/ijcp.12333. Epub 2013 Oct 21.
• Results Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb 19:S0016-5085(16)00223-7. doi: 10.1053/j.gastro.2016.02.032. Online ahead of print.

Drugs

Indications