L. Casei DG® in Patients With Irritable Bowel Syndrome.

IBS - Irritable Bowel Syndrome Clinical Trial

— PROBE2  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03449628
• Other study ID #: PSC-DS PROBE2-IBS/17
• Status: Completed
• Phase: N/A
• Start date: November 6, 2017
• Est. completion date: December 30, 2021

Study information

• Verified date: May 2022
• Source: SOFAR S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 264
• Est. completion date: December 30, 2021
• Est. primary completion date: May 4, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• IBS - Irritable Bowel Syndrome
• Irritable Bowel Syndrome
• Syndrome

Intervention

Dietary Supplement:
• L.casei DG
(At least 24 billion live cells per capsule) 1 capsule, b.i.d. for 12 weeks
• PLACEBO
1 capsule, b.i.d. for 12 weeks

Locations

Country	Name	City	State
Italy	Gastroenterologia Universitaria Policlinico Giovanni XXIII	Bari
Italy	Azienda ULSS 1	Belluno
Italy	Azienda Ospedaliero-Universitaria S. Orsola Malpighi	Bologna
Italy	A.O. "G. Brotzu"- Ospedale San Michele	Cagliari	CA
Italy	AOU di Cagliari - Policlinico di Monserrato	Cagliari	CA
Italy	Ospedale SS. Annunziata	Chieti
Italy	Ospedale Valduce	Como	CO
Italy	ASST-FTB-Sacco	Milano	MI
Italy	Fondazione IRCCS Policlinico	Milano
Italy	Policlinico	Napoli
Italy	Policlinico Federico II	Napoli
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Fondazione IRCCS Policlinico S. Matteo	Pavia
Italy	U.O. Gastroenterologia Universitaria	Pisa
Italy	A.O. San Camillo-Forlanini	Roma
Italy	Ospedale Sant'Andrea	Roma
Italy	Policlinico Universitario Campus Biomedico	Roma
Italy	Policlinico San Donato	San Donato Milanese	MI
Italy	A.O. Bolognini	Seriate	BG
Italy	Ospedale Sant'Andrea	Vercelli	VC

Sponsors (2)

Lead Sponsor	Collaborator
SOFAR S.p.A.	1Med

Country where clinical trial is conducted

Italy, 

References & Publications (10)

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. pii: S0016-5085(16)00219-5. doi: 10.1053/j.gastro.2016.02.028. [Epub ahead of print] — View Citation

Jalanka-Tuovinen J, Salojärvi 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. — View 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. — View Citation

Mearin F, Lacy BE, Chang L, Chey WD, Lembo AJ, Simren M, Spiller R. Bowel Disorders. Gastroenterology. 2016 Feb 18. pii: S0016-5085(16)00222-5. doi: 10.1053/j.gastro.2016.02.031. [Epub ahead of print] — View 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. Review. — View 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. — View 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. — View Citation

Schoepfer AM, Schaffer T, Seibold-Schmid B, Müller 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. — 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

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients who have a response in pain	Patients who record on = 50% of the days a reduction of = 30% from their average baseline score for their worst abdominal pain.The standard 11-point numeric rating scale (from 0=none to 10=worst possible pain) will be used to measure abdominal pain.	12 weeks
Primary	Proportion of patients who have a response in stool consistencies	Patients who record a stool-consistency score < 5 in the same days in which they record a reduction of = 30% from their average baseline score for their worst abdominal pain .For abnormal defecation, stool frequency and form will be measured using the Bristol Stool Form Scale (BSFS).	12 weeks
Secondary	Evaluation of Pain relief	reduction of = 30% from baseline in the score for the worst abdominal pain on = 50% of days	16 weeks
Secondary	Evaluation of global symptom score	Improvement in the global symptom score: a score of 0 or 1, or an improvement = 2 over the baseline score, on = 50% of days	16 weeks
Secondary	Relief of IBS symptoms	Adequate relief of IBS symptoms on = 50% of the past weeks (a response of "yes" on =50% of the weeks to the following question: "Over the past week, have you had adequate relief of your IBS symptoms?)"	16 weeks
Secondary	IBS-SSS score questionnaire (Severity Scoring System )	To assess the severity of symptoms related to Irritable Bowel Syndrome, assessed at baseline and at the end of treatment after 12 weeks (it is considered clinically significant a score reduction of at least 50 points). The questionnaire is composed by five questions wich generate a maximum score of 100 each using prompted visual analogue scales, leading to a total possible score of 500.	16 weeks
Secondary	Improvement in stool consistency	stool consistency score = 5 assessed with BSFS (Bristol Stool Form Scale) BSFS evaluates stool form and consistency (score from 1=dry stool to 7=liquid stoo. The ideal stool is generally 3 or 4)	16 weeks
Secondary	Satisfaction with treatment	Overall satisfaction with treatment assessed by VAS scale (Visual Analogue Scale)	16 weeks
Secondary	Quality of life	Quality of life assessment by validated Short-Form 12 Items Health Survey (SF-12) on a scale of 0 to 100	16 weeks
Secondary	Intake of rescue medication	type and frequencies of rescue medication	16 weeks
Secondary	gut microbiota composition	Evaluation of changes in the gut microbiota composition and the relative abundance of bacterial OTUs (Operational Taxonomic Unit).	16 weeks
Secondary	Short Chain Fatty Acids (SCFA)	Evaluation of Short Chain Fatty Acids levels in fecal samples	16 weeks
Secondary	Free Aminoacids	Evaluation of Free aminoacids levels in fecal samples	16 weeks
Secondary	Biogenic Amines	Evaluation of biogenic amines levels in fecal samples	16 weeks
Secondary	Gut permeability for zonulin	evaluation of serum levels of zonulin	16 weeks
Secondary	Gut permeability for citrulline	evaluation of serum levels of citrulline	16 weeks
Secondary	Gut permeability for PV-1 (Plasmalemma vesicle-associated) protein	evaluation of serum levels of PV-1 (Plasmalemma vesicle-associated) protein	16 weeks
Secondary	L. casei DG® strain in the feces	the recovery of L. casei DG® strain in the feces	16 weeks