Clinical trial NCT03449628: L. Casei DG® in Patients With Irritable Bowel Syndrome.
Official title: L. Casei DG® (Lactobacillus Paracasei CNCMI1572) in the Treatment of Patients With Irritable Bowel Syndrome: a Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo Controlled Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: IBS - Irritable Bowel Syndrome
Lead sponsor: SOFAR S.p.A.
Sponsor class: INDUSTRY
Collaborators: name: 1Med
First posted: 2018-02-28
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To assess the effect of L. casei DG® (Lactobacillus paracasei CNCMI1572; Enterolactis® plus) on abdominal symptoms and gut microbiota metabolism/composition in non constipated patients with IBS (Irritable Bowel Syndrome). Patients will be randomized to receive L. casei DG® capsules, b.i.d. for 12 weeks the a 4 weeks Follow Up period will follow.


Eligibility criteria: Inclusion Criteria:

* Age \> 18 years and ≤ 65 years
* A positive diagnosis of non constipated IBS (i.e., IBS-D and IBS-M, both males and females), according to Rome IV criteria.
* A negative outcome of colonoscopy performed within 5 years before screening if patient is at least 50 years old, or if patient meet any of the following alarm features:

  1. Has a documented weight loss within the past 6 months; or
  2. Has nocturnal symptoms; or
  3. Has a familiar history of colon cancer; or
  4. Has blood mixed with their stool (excluding blood from hemorroids).
* Negative relevant additional screening or consultation whenever appropriate
* Ability to conform to the study protocol.

Exclusion Criteria:

* Patients with IBS-C or IBS-U according to Rome IV 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, (i.e..liver or kidney functional levels 2-times greater than the upper reference values)
* Ascertained intestinal organic diseases, including celiac disease, food allergies or inflammatory bowel diseases (Crohn's disease, ulcerative colitis, diverticular disease, infectious colitis, ischemic colitis, microscopic colitis).
* Previous major abdominal surgery.
* 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.
* Use of probiotics or topical and/or systemic antibiotic therapy during the last month.
* Systematic/frequent use of contact laxatives.
* Pregnant females or females of childbearing potential in the absence of effective contraceptive methods.
* Inability to conform to protocol.
* Treatment with any investigational drug within the previous 30 days.
* Recent history or suspicion of alcohol abuse or drug addiction.
* Presence of red or white flags at the Rome IV Psychosocial Alarm Questionnaire for Functional gastrointestinal Disorders.

Primary outcomes:
measure: Proportion of patients who have a response in pain
timeFrame: 12 weeks
measure: Proportion of patients who have a response in stool consistencies
timeFrame: 12 weeks
Secondary outcomes:
measure: Evaluation of Pain relief
timeFrame: 16 weeks
measure: Evaluation of global symptom score
timeFrame: 16 weeks
measure: Relief of IBS symptoms
timeFrame: 16 weeks
measure: IBS-SSS score questionnaire (Severity Scoring System )
timeFrame: 16 weeks
measure: Improvement in stool consistency
timeFrame: 16 weeks
measure: Satisfaction with treatment
timeFrame: 16 weeks
measure: Quality of life
timeFrame: 16 weeks
measure: Intake of rescue medication
timeFrame: 16 weeks
measure: gut microbiota composition
timeFrame: 16 weeks
measure: Short Chain Fatty Acids (SCFA)
timeFrame: 16 weeks
measure: Free Aminoacids
timeFrame: 16 weeks
measure: Biogenic Amines
timeFrame: 16 weeks
measure: Gut permeability for zonulin
timeFrame: 16 weeks
measure: Gut permeability for citrulline
timeFrame: 16 weeks
measure: Gut permeability for PV-1 (Plasmalemma vesicle-associated) protein
timeFrame: 16 weeks
measure: L. casei DG® strain in the feces
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Seriate
country: Italy
facility: A.O. Bolognini
state: BG
city: Cagliari
country: Italy
facility: A.O. "G. Brotzu"- Ospedale San Michele
state: CA
city: Cagliari
country: Italy
facility: AOU di Cagliari - Policlinico di Monserrato
state: CA
city: Como
country: Italy
facility: Ospedale Valduce
state: CO
city: Milano
country: Italy
facility: ASST-FTB-Sacco
state: MI
city: San Donato Milanese
country: Italy
facility: Policlinico San Donato
state: MI
city: Vercelli
country: Italy
facility: Ospedale Sant'Andrea
state: VC
city: Bari
country: Italy
facility: Gastroenterologia Universitaria Policlinico Giovanni XXIII
city: Belluno
country: Italy
facility: Azienda ULSS 1
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria S. Orsola Malpighi
city: Chieti
country: Italy
facility: Ospedale SS. Annunziata
city: Milano
country: Italy
facility: Fondazione IRCCS Policlinico
city: Napoli
country: Italy
facility: Policlinico
city: Napoli
country: Italy
facility: Policlinico Federico II
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico S. Matteo
city: Pisa
country: Italy
facility: U.O. Gastroenterologia Universitaria
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico
city: Roma
country: Italy
facility: A.O. San Camillo-Forlanini
city: Roma
country: Italy
facility: Ospedale Sant'Andrea
Study officials:
affiliation: AUO Sant'Orsola Malpighi Bologna (Gastroenterology)
name: Giovanni Barbara, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mearin F, Lacy BE, Chang L, Chey WD, Lembo AJ, Simren M, Spiller R. Bowel Disorders. Gastroenterology. 2016 Feb 18:S0016-5085(16)00222-5. doi: 10.1053/j.gastro.2016.02.031. Online ahead of print.
citation: Barbara G, Feinle-Bisset C, Ghoshal UC, Quigley EM, Santos J, Vanner S, Vergnolle N, Zoetendal EG. The Intestinal Microenvironment and Functional Gastrointestinal Disorders. Gastroenterology. 2016 Feb 18:S0016-5085(16)00219-5. doi: 10.1053/j.gastro.2016.02.028. Online ahead of print.
citation: Spiller R, Garsed K. Postinfectious irritable bowel syndrome. Gastroenterology. 2009 May;136(6):1979-88. doi: 10.1053/j.gastro.2009.02.074. Epub 2009 May 7.
citation: Schoepfer AM, Schaffer T, Seibold-Schmid B, Muller S, Seibold F. Antibodies to flagellin indicate reactivity to bacterial antigens in IBS patients. Neurogastroenterol Motil. 2008 Oct;20(10):1110-8. doi: 10.1111/j.1365-2982.2008.01166.x. Epub 2008 Aug 6.
citation: Langhorst J, Junge A, Rueffer A, Wehkamp J, Foell D, Michalsen A, Musial F, Dobos GJ. Elevated human beta-defensin-2 levels indicate an activation of the innate immune system in patients with irritable bowel syndrome. Am J Gastroenterol. 2009 Feb;104(2):404-10. doi: 10.1038/ajg.2008.86. Epub 2009 Jan 20.
citation: Pimentel M, Morales W, Rezaie A, Marsh E, Lembo A, Mirocha J, Leffler DA, Marsh Z, Weitsman S, Chua KS, Barlow GM, Bortey E, Forbes W, Yu A, Chang C. Development and validation of a biomarker for diarrhea-predominant irritable bowel syndrome in human subjects. PLoS One. 2015 May 13;10(5):e0126438. doi: 10.1371/journal.pone.0126438. eCollection 2015.
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: Jalanka-Tuovinen J, Salojarvi J, Salonen A, Immonen O, Garsed K, Kelly FM, Zaitoun A, Palva A, Spiller RC, de Vos WM. Faecal microbiota composition and host-microbe cross-talk following gastroenteritis and in postinfectious irritable bowel syndrome. Gut. 2014 Nov;63(11):1737-45. doi: 10.1136/gutjnl-2013-305994. Epub 2013 Dec 5.
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: 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.