Clinical trial NCT02371499: Effect of Lactobacillus Casei DG (Enterolactis Plus®) in Patient With Irritable Bowel Syndrome: a Pilot Study
Official title: Effect of Lactobacillus Casei dg (Enterolactis Plus®) in Patient With Irritable Bowel Syndrome: Multicenter, Randomized, Double-blind, Cross-over, Placebo Controlled, Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome
Keywords: Irritable Bowel Syndrome
Lactobacillus casei dg
microbiota
Lead sponsor: SOFAR S.p.A.
Sponsor class: INDUSTRY
First posted: 2015-02-25
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The aim of the study is to collect data for the assessment of the Lactobacillus casei DG (Enterolactis plus®) effect on overall abdominal pain/discomfort, symptoms and gut microbiota composition in patients with Irritable Bowel Syndrome.

Detailed description: The aim of the study is to collect data for the assessment of the Lactobacillus casei DG (Enterolactis plus®) effect on overall abdominal pain/discomfort, symptoms and gut microbiota composition in patients with Irritable Bowel Syndrome. The investigators suppose that, due to the immunomodulatory action of probiotics, overall abdominal pain/discomfort and symptoms will improve, fecal Immunoglobulin A levels will change, pro-inflammatory cytokine levels will decrease and the production of regulatory cytokines as Interleukin 10 will improve following consumption of Lactobacillus casei DG (Enterolactis plus®).

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years and ≤ 65 years.
* A positive diagnosis of Irritable Bowel Syndrome regardless of bowel habit (both males and females), according to Rome III criteria.
* Negative outcome of barium enema or left colonoscopy within the previous two years.
* Negative relevant additional screening or consultation whenever appropriate.
* Ability of conforming to the study protocol.

Exclusion Criteria:

* Presence of any relevant organic, systemic or metabolic disease (particularly significant history of cardiac, renal, neurological, psychiatric, oncology, endocrinology, metabolic or hepatic disease), or abnormal laboratory values that will be deemed clinically significant on the basis of predefined values.
* Ascertained intestinal organic diseases, including ascertained celiac disease or inflammatory bowel diseases (Crohn's disease, ulcerative colitis, diverticular disease, infectious colitis, ischemic colitis, microscopic colitis).
* Previous major abdominal surgeries.
* Active malignancy of any type, or history of a malignancy (patients with a history of other malignancies that have been surgically removed and who have no evidence of recurrence for at least five years before study enrolment are also acceptable).
* Untreated food intolerance such as ascertained or suspected lactose intolerance, as defined by anamnestic evaluation or, if appropriate, lactose breath test.
* Assumption of probiotics or topic and/or systemic antibiotic therapy during the last month.
* Systematical/frequent assumption of contact laxatives.
* Females of childbearing potential, in the absence of effective contraceptive methods.
* Pregnant women.
* Inability to conform with protocol.
* Treatment with any investigational drug within the previous 30 days.
* Recent history or suspicion of alcohol abuse or drug addiction.
* Previous participation in this study.

Primary outcomes:
measure: Abdominal pain/discomfort as measured by 11-point Numerical Rating Scale
timeFrame: 1 day
measure: Irritable Bowel Syndrome degree-of-relief as measured by 7-point balanced ordinal scale
timeFrame: 1 week
measure: Stool frequency and consistency as assessed by Bristol Scale
timeFrame: 1 day
measure: Microbiota of fecal sample as characterized by Ion Torrent Personal Genome Machine sequencing of 16S ribosomal RNA-based amplicons
timeFrame: 4 weeks
measure: Overall satisfaction with treatment as measured by Visual Analogue Scale
timeFrame: 4 weeks
measure: Quality of life as measured by Short-Form 12 Items Health Survey
timeFrame: 4 weeks
measure: Anxiety and Depression as assessed by Hospital Anxiety and Depression Scale (HADS)
timeFrame: 4 weeks
measure: Consumption of rescue medication
timeFrame: 1 day
measure: Secretory Immunoglobulin A and cytokines levels in fecal samples as measured by ELISA test.
timeFrame: 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: San Donato
country: Italy
facility: Policlinico S.Donato
state: Milano
city: Belluno
country: Italy
facility: Azienda ULSS 1
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria S. Orsola Malpighi
city: Pisa
country: Italy
facility: U.O. Gastroenterologia Universitaria
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico
Study officials:
affiliation: Policlinico S. Orsola-Malpighi - Azienda Ospedaliero-Universitaria di Bologna
name: Giorvanni Barbara, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Barbara G, Stanghellini V. Biomarkers in IBS: when will they replace symptoms for diagnosis and management? Gut. 2009 Dec;58(12):1571-5. doi: 10.1136/gut.2008.169672. No abstract available.
citation: Cremon C, Carini G, De Giorgio R, Stanghellini V, Corinaldesi R, Barbara G. Intestinal dysbiosis in irritable bowel syndrome: etiological factor or epiphenomenon? Expert Rev Mol Diagn. 2010 May;10(4):389-93. doi: 10.1586/erm.10.33.
citation: 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.
citation: Rajilic-Stojanovic M, Biagi E, Heilig HG, Kajander K, Kekkonen RA, Tims S, de Vos WM. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology. 2011 Nov;141(5):1792-801. doi: 10.1053/j.gastro.2011.07.043. Epub 2011 Aug 5.
citation: Jeffery IB, O'Toole PW, Ohman L, Claesson MJ, Deane J, Quigley EM, Simren M. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut. 2012 Jul;61(7):997-1006. doi: 10.1136/gutjnl-2011-301501. Epub 2011 Dec 16.
citation: Moayyedi P, Ford AC, Talley NJ, Cremonini F, Foxx-Orenstein AE, Brandt LJ, Quigley EM. The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut. 2010 Mar;59(3):325-32. doi: 10.1136/gut.2008.167270. Epub 2008 Dec 17.
citation: Madsen K, Cornish A, Soper P, McKaigney C, Jijon H, Yachimec C, Doyle J, Jewell L, De Simone C. Probiotic bacteria enhance murine and human intestinal epithelial barrier function. Gastroenterology. 2001 Sep;121(3):580-91. doi: 10.1053/gast.2001.27224.
citation: Eun CS, Kim YS, Han DS, Choi JH, Lee AR, Park YK. Lactobacillus casei prevents impaired barrier function in intestinal epithelial cells. APMIS. 2011 Jan;119(1):49-56. doi: 10.1111/j.1600-0463.2010.02691.x. Epub 2010 Oct 25.
citation: Corinaldesi R, Stanghellini V, Cremon C, Gargano L, Cogliandro RF, De Giorgio R, Bartesaghi G, Canovi B, Barbara G. Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof-of-concept study. Aliment Pharmacol Ther. 2009 Aug;30(3):245-52. doi: 10.1111/j.1365-2036.2009.04041.x. Epub 2009 May 12.
citation: Quigley EM, Tack J, Chey WD, Rao SS, Fortea J, Falques M, Diaz C, Shiff SJ, Currie MG, Johnston JM. Randomised clinical trials: linaclotide phase 3 studies in IBS-C - a prespecified further analysis based on European Medicines Agency-specified endpoints. Aliment Pharmacol Ther. 2013 Jan;37(1):49-61. doi: 10.1111/apt.12123. Epub 2012 Nov 1.
citation: Cremon C, Guglielmetti S, Gargari G, Taverniti V, Castellazzi AM, Valsecchi C, Tagliacarne C, Fiore W, Bellini M, Bertani L, Gambaccini D, Cicala M, Germana B, Vecchi M, Pagano I, Barbaro MR, Bellacosa L, Stanghellini V, Barbara G. Effect of Lactobacillus paracasei CNCM I-1572 on symptoms, gut microbiota, short chain fatty acids, and immune activation in patients with irritable bowel syndrome: A pilot randomized clinical trial. United European Gastroenterol J. 2018 May;6(4):604-613. doi: 10.1177/2050640617736478. Epub 2017 Oct 8.