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

Official title

The Role of Irritable Bowel Syndrome in Lactose Intolerance (LION Trial): Protocol of a Multicentre Randomized Controlled Clinical Trial

Overview

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.

Detailed 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.

Interventions

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

Primary outcome measures

• change of the symptoms measured by TSS (total symptom score) [Time frame: The one- and two-week total symptom score (TSS) change compared to baseline value.]

Secondary outcome measures (6)

• improvement in stool consistency [Time frame: The two time points at which the measurement is assessed are the time of enrollment and after 2 weeks.]
• the absence of a bowel movement [Time frame: The three time points at which the measurement is assessed are the time of enrollment, after 1 and 2 weeks.]
• relief of IBS-related bloating [Time frame: The three time points at which the measurement is assessed are the time of enrollment, after 1 and 2 weeks.]
• Onset and duration of relief of bloating [Time frame: The three time points at which the measurement is assessed are the time of enrollment, after 1 and 2 weeks.]
• incidence of Small intestinal bacterial overgrowth (SIBO) [Time frame: At the time of patient enrollment and after two weeks of treatments this test will be carried out again.]
• results of LHBT and LTT [Time frame: At the time of patient enrollment and after two weeks of treatments LHBT and LTT will be carried out again.]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Hungary · 1 center

• Institute for Translational Medicine, University of Pécs — Pécs

Publications

• 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. PMID 16678561
• 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. PMID 28702130
• 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. PMID 22426087
• 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. PMID 11786669
• 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. PMID 19384249
• 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. PMID 21333898
• 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. PMID 15926760
• 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. PMID 16469679

Identifiers

NCT: NCT05100719 · IV/4455-3/2021/EKU

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗