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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05100719
Other study ID # IV/4455-3/2021/EKU
Secondary ID
Status Not yet recruiting
Phase N/A
First received
Last updated
Start date September 2022
Est. completion date December 2026

Study information

Verified date October 2021
Source University of Pecs
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

Irritable bowel syndrome (IBS) is one of the most frequently diagnosed gastroenterological disorders and can lead to significant deterioration of quality of life and an increase in health care and societal costs. Patients with lactose intolerance are unable to fully digest lactose caused by lactose malabsorption. The undigested lactose moves into the large intestine, fermented by bacteria, and causes bloating, gas, and diarrhea symptoms. The two, most frequently used diagnostic methods are the lactose H2 breath test (LHBT) and the lactose tolerance test (LTT). The restriction of lactose input or the replacement of the lactase enzyme can lead to the relief of the symptoms. Lactose intolerance is a common disorder among patients with IBS, it is more frequent than in the general population. There are no studies that assess the link between lactose intolerance and IBS. Our primary objective is the examination of the relationship between lactose intolerance and IBS with or without the replacement of lactase enzyme. Our secondary objectives are to compare the lactase/beta-galactosidase enzyme replacement with placebo with the evaluation of a TSS (Total symptom score), VAS (Visual Analog Scale), QoL (Quality of life) questionnaires. The other secondary outcomes are to compare the severity of baseline symptoms during and after lactose administration. Patients diagnosed with IBS according to the Rome IV criteria will test with LTT and LHBT. Who has positive LTT and LHBT will randomize into two groups: (1) alverine-citrate + simethicone and lactase; (2) alverin-citrate + simethicone with placebo.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 200
Est. completion date December 2026
Est. primary completion date September 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility Inclusion Criteria: - age 18-80 years - patients diagnosed with irritable bowel syndrome based on the ROME IV. criteria - positive LHBT (lactose H2 breath test) and LTT (lactose tolerance test) results - negative abdominal ultrasound/CAT scan/MRI results within one year - signed the informed consent Exclusion Criteria: - organic gastroenterological disorders which can explain symptoms (e.g. positive serological screening: anti-gliadin IgG / IgA, anti-tissue transglutaminase IgG / IgA, high level of fecal calprotectin tested by endoscopy or positive colonoscopy for IBD, currently active diverticulitis - Alarm symptoms: fever (> 38 Co), anaemia (Hgb < 120 g/l), unintended weight loss (> 4.5 kg / 3 months), gastrointestinal bleeding (hematemesis, hematochesia, melena) - cardiac failure (NYHA III-IV) - liver cirrhosis (Child-Pugh C) - active malignancy - major abdominal surgery in the history - pregnant or breastfeeding women - any circumstances which can lead to false results of LHBT and LTT: cigarette smoking or physical exercise within 2 hours before the test, ingestion of dietary fibers on the evening before the test, recent use of antibiotics, lung disease, baseline H2 concentration in the exhaled air is higher than 20 ppm, not properly treated diabetes mellitus, following lactose restricted or another special diet within 1 week prior to study enrolment (ingestion of less than 12 g lactose - less than 250 ml milk - per day) - small intestinal bacterial overgrowth (SIBO): if there is a rapid increase of H2 level in the exhaled air (=20 ppm above baseline within 90 minutes), SIBO is suspected and antibiotic therapy will be started (peroral rifaximin for 5 days) after negative Helicobacter pylori serology. After this procedure, lactulose H2 breath test will be performed to exclude SIBO (=20 ppm H2 rise only after 90 min). In case of negative lactulose H2 breath test, another LHBT will be carried out - slow oro-cecal transit: clinical signs and typical findings on the tests (the LHBT is normal, but the increase of blood glucose level is less than 1.1 mmol/l and/or no H2 rise during lactulose H2 breath test) - milk allergy (positive IgE test)

Study Design


Intervention

Drug:
alverine-citrate + simethicone and lactase
Patients who randomized in the first arm are treated with alverine-citrate + simethicone and lactase.
alverin-citrate + simethicone with placebo
Patients in the second arm receive alverin-citrate + simethicone with placebo without lactase.

Locations

Country Name City State
Hungary Institute for Translational Medicine, University of Pécs Pécs

Sponsors (1)

Lead Sponsor Collaborator
University of Pecs

Country where clinical trial is conducted

Hungary, 

References & Publications (31)

Agarwal N, Spiegel BM. The effect of irritable bowel syndrome on health-related quality of life and health care expenditures. Gastroenterol Clin North Am. 2011 Mar;40(1):11-9. doi: 10.1016/j.gtc.2010.12.013. Review. — View Citation

Böhmer CJ, Tuynman HA. The clinical relevance of lactose malabsorption in irritable bowel syndrome. Eur J Gastroenterol Hepatol. 1996 Oct;8(10):1013-6. — View Citation

Böhn L, Störsrud S, Liljebo T, Collin L, Lindfors P, Törnblom H, Simrén 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. — View Citation

Borghini R, Donato G, Alvaro D, Picarelli A. New insights in IBS-like disorders: Pandora's box has been opened; a review. Gastroenterol Hepatol Bed Bench. 2017 Spring;10(2):79-89. Review. — View Citation

Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jeric K, Hróbjartsson A, Mann H, Dickersin K, Berlin JA, Doré 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. — View Citation

Dean BB, Aguilar D, Barghout V, Kahler KH, Frech F, Groves D, Ofman JJ. Impairment in work productivity and health-related quality of life in patients with IBS. Am J Manag Care. 2005 Apr;11(1 Suppl):S17-26. — View Citation

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. Epub 2007 Aug 17. — View Citation

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. — View Citation

Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb 19. pii: S0016-5085(16)00223-7. doi: 10.1053/j.gastro.2016.02.032. [Epub ahead of print] — View Citation

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. — View Citation

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. Epub 2007 Oct 15. — View Citation

Hillilä M, Färkkilä MA, Sipponen T, Rajala J, Koskenpato J. Does oral a-galactosidase relieve irritable bowel symptoms? Scand J Gastroenterol. 2016 Jan;51(1):16-21. doi: 10.3109/00365521.2015.1063156. Epub 2015 Jul 2. — View Citation

Hillilä MT, Färkkilä NJ, Färkkilä MA. Societal costs for irritable bowel syndrome--a population based study. Scand J Gastroenterol. 2010 May;45(5):582-91. doi: 10.3109/00365521003637211. — View Citation

Lisker R, Solomons NW, Pérez Briceño R, Ramírez 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. — View Citation

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. Epub 2007 Oct 23. Review. — View Citation

Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006 Apr;130(5):1480-91. Review. Erratum in: Gastroenterology. 2006 Aug;131(2):688. — View Citation

Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012 Jul;10(7):712-721.e4. doi: 10.1016/j.cgh.2012.02.029. Epub 2012 Mar 15. — View Citation

Miller V, Hopkins L, Whorwell PJ. Suicidal ideation in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol. 2004 Dec;2(12):1064-8. — View Citation

Misselwitz B, Pohl D, Frühauf 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. — View Citation

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. — View Citation

Müller-Lissner SA, Bollani S, Brummer RJ, Coremans G, Dapoigny M, Marshall JK, Muris JW, Oberndorff-Klein Wolthuis A, Pace F, Rodrigo L, Stockbrügger R, Vatn MH. Epidemiological aspects of irritable bowel syndrome in Europe and North America. Digestion. 2001;64(3):200-4. — View Citation

Simrén 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. — View Citation

Simrén M, Svedlund J, Posserud I, Björnsson 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. Erratum in: Clin Gastroenterol Hepatol. 2006 Jun;4(6):803. — View Citation

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. — View Citation

Varjú P, Gede N, Szakács Z, Hegyi P, Cazacu IM, Pécsi D, Fábián A, Szepes Z, Vincze Á, Tenk J, Balaskó 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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 31 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary change of the symptoms measured by TSS (total symptom score) The primary outcome is the number of enrolled patients with significant improvement in each treatment arm. Significant improvement is considered if there is >50% reduction in the TSS, compared to the baseline symptoms. The one- and two-week total symptom score (TSS) change compared to baseline value.
Secondary improvement in stool consistency stool consistency score of <5, according to the Bristol stool chart The two time points at which the measurement is assessed are the time of enrollment and after 2 weeks.
Secondary the absence of a bowel movement The absence of a bowel movement is accompanied by an improvement of =30 mm in the VAS (visual analogue scale) for the worst abdominal pain. The three time points at which the measurement is assessed are the time of enrollment, after 1 and 2 weeks.
Secondary relief of IBS-related bloating The number of patients with acceptable relief of IBS-related bloating determined by a questionnaire, from the response (yes or no) compare to the baseline IBS-related bloating. The three time points at which the measurement is assessed are the time of enrollment, after 1 and 2 weeks.
Secondary Onset and duration of relief of bloating Onset and duration of relief of bloating is measured by a questionnaire. The three time points at which the measurement is assessed are the time of enrollment, after 1 and 2 weeks.
Secondary incidence of Small intestinal bacterial overgrowth (SIBO) Early (within 90 minutes), significant (=20 ppm) H2 rise during LHBT or lactulose breath test compared to the baseline value. At the time of patient enrollment and after two weeks of treatments this test will be carried out again.
Secondary results of LHBT and LTT Results of LHBT (lactose H2 breath test) and LTT (lactose tolerance test). At the time of patient enrollment and after two weeks of treatments LHBT and LTT will be carried out again.
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