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L. Casei DG® in Patients With Irritable Bowel Syndrome. (PROBE2)

Primary Purpose

IBS - Irritable Bowel Syndrome

Status
Completed
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
L.casei DG
PLACEBO
Sponsored by
SOFAR S.p.A.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for IBS - Irritable Bowel Syndrome

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • A.O. Bolognini
  • A.O. "G. Brotzu"- Ospedale San Michele
  • AOU di Cagliari - Policlinico di Monserrato
  • Ospedale Valduce
  • ASST-FTB-Sacco
  • Policlinico San Donato
  • Ospedale Sant'Andrea
  • Gastroenterologia Universitaria Policlinico Giovanni XXIII
  • Azienda ULSS 1
  • Azienda Ospedaliero-Universitaria S. Orsola Malpighi
  • Ospedale SS. Annunziata
  • Fondazione IRCCS Policlinico
  • Policlinico
  • Policlinico Federico II
  • Azienda Ospedaliera di Padova
  • Fondazione IRCCS Policlinico S. Matteo
  • U.O. Gastroenterologia Universitaria
  • Policlinico Universitario Campus Biomedico
  • A.O. San Camillo-Forlanini
  • Ospedale Sant'Andrea

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

L. casei DG®

Placebo

Arm Description

Interventions: Lactobacillus paracasei CNCMI1572 (At least 24 billion live cells per capsule) 1 capsule, b.i.d. for 12 weeks

Interventions : capsules for oral use, indistinguishable from active product. 1 capsule, b.i.d. for 12 weeks

Outcomes

Primary Outcome Measures

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.
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).

Secondary Outcome Measures

Evaluation of Pain relief
reduction of ≥ 30% from baseline in the score for the worst abdominal pain on ≥ 50% of days
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
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?)"
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.
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)
Satisfaction with treatment
Overall satisfaction with treatment assessed by VAS scale (Visual Analogue Scale)
Quality of life
Quality of life assessment by validated Short-Form 12 Items Health Survey (SF-12) on a scale of 0 to 100
Intake of rescue medication
type and frequencies of rescue medication
gut microbiota composition
Evaluation of changes in the gut microbiota composition and the relative abundance of bacterial OTUs (Operational Taxonomic Unit).
Short Chain Fatty Acids (SCFA)
Evaluation of Short Chain Fatty Acids levels in fecal samples
Free Aminoacids
Evaluation of Free aminoacids levels in fecal samples
Biogenic Amines
Evaluation of biogenic amines levels in fecal samples
Gut permeability for zonulin
evaluation of serum levels of zonulin
Gut permeability for citrulline
evaluation of serum levels of citrulline
Gut permeability for PV-1 (Plasmalemma vesicle-associated) protein
evaluation of serum levels of PV-1 (Plasmalemma vesicle-associated) protein
L. casei DG® strain in the feces
the recovery of L. casei DG® strain in the feces

Full Information

First Posted
February 7, 2018
Last Updated
May 5, 2022
Sponsor
SOFAR S.p.A.
Collaborators
1Med
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1. Study Identification

Unique Protocol Identification Number
NCT03449628
Brief Title
L. Casei DG® in Patients With Irritable Bowel Syndrome.
Acronym
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.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
November 6, 2017 (Actual)
Primary Completion Date
May 4, 2021 (Actual)
Study Completion Date
December 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SOFAR S.p.A.
Collaborators
1Med

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
IBS - Irritable Bowel Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
264 (Actual)

8. Arms, Groups, and Interventions

Arm Title
L. casei DG®
Arm Type
Experimental
Arm Description
Interventions: Lactobacillus paracasei CNCMI1572 (At least 24 billion live cells per capsule) 1 capsule, b.i.d. for 12 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Interventions : capsules for oral use, indistinguishable from active product. 1 capsule, b.i.d. for 12 weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
L.casei DG
Intervention Description
(At least 24 billion live cells per capsule) 1 capsule, b.i.d. for 12 weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
PLACEBO
Intervention Description
1 capsule, b.i.d. for 12 weeks
Primary Outcome Measure Information:
Title
Proportion of patients who have a response in pain
Description
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.
Time Frame
12 weeks
Title
Proportion of patients who have a response in stool consistencies
Description
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).
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Evaluation of Pain relief
Description
reduction of ≥ 30% from baseline in the score for the worst abdominal pain on ≥ 50% of days
Time Frame
16 weeks
Title
Evaluation of global symptom score
Description
Improvement in the global symptom score: a score of 0 or 1, or an improvement ≥ 2 over the baseline score, on ≥ 50% of days
Time Frame
16 weeks
Title
Relief of IBS symptoms
Description
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?)"
Time Frame
16 weeks
Title
IBS-SSS score questionnaire (Severity Scoring System )
Description
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.
Time Frame
16 weeks
Title
Improvement in stool consistency
Description
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)
Time Frame
16 weeks
Title
Satisfaction with treatment
Description
Overall satisfaction with treatment assessed by VAS scale (Visual Analogue Scale)
Time Frame
16 weeks
Title
Quality of life
Description
Quality of life assessment by validated Short-Form 12 Items Health Survey (SF-12) on a scale of 0 to 100
Time Frame
16 weeks
Title
Intake of rescue medication
Description
type and frequencies of rescue medication
Time Frame
16 weeks
Title
gut microbiota composition
Description
Evaluation of changes in the gut microbiota composition and the relative abundance of bacterial OTUs (Operational Taxonomic Unit).
Time Frame
16 weeks
Title
Short Chain Fatty Acids (SCFA)
Description
Evaluation of Short Chain Fatty Acids levels in fecal samples
Time Frame
16 weeks
Title
Free Aminoacids
Description
Evaluation of Free aminoacids levels in fecal samples
Time Frame
16 weeks
Title
Biogenic Amines
Description
Evaluation of biogenic amines levels in fecal samples
Time Frame
16 weeks
Title
Gut permeability for zonulin
Description
evaluation of serum levels of zonulin
Time Frame
16 weeks
Title
Gut permeability for citrulline
Description
evaluation of serum levels of citrulline
Time Frame
16 weeks
Title
Gut permeability for PV-1 (Plasmalemma vesicle-associated) protein
Description
evaluation of serum levels of PV-1 (Plasmalemma vesicle-associated) protein
Time Frame
16 weeks
Title
L. casei DG® strain in the feces
Description
the recovery of L. casei DG® strain in the feces
Time Frame
16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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: Has a documented weight loss within the past 6 months; or Has nocturnal symptoms; or Has a familiar history of colon cancer; or 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giovanni Barbara, MD
Organizational Affiliation
AUO Sant'Orsola Malpighi Bologna (Gastroenterology)
Official's Role
Principal Investigator
Facility Information:
Facility Name
A.O. Bolognini
City
Seriate
State/Province
BG
Country
Italy
Facility Name
A.O. "G. Brotzu"- Ospedale San Michele
City
Cagliari
State/Province
CA
Country
Italy
Facility Name
AOU di Cagliari - Policlinico di Monserrato
City
Cagliari
State/Province
CA
Country
Italy
Facility Name
Ospedale Valduce
City
Como
State/Province
CO
Country
Italy
Facility Name
ASST-FTB-Sacco
City
Milano
State/Province
MI
Country
Italy
Facility Name
Policlinico San Donato
City
San Donato Milanese
State/Province
MI
Country
Italy
Facility Name
Ospedale Sant'Andrea
City
Vercelli
State/Province
VC
Country
Italy
Facility Name
Gastroenterologia Universitaria Policlinico Giovanni XXIII
City
Bari
Country
Italy
Facility Name
Azienda ULSS 1
City
Belluno
Country
Italy
Facility Name
Azienda Ospedaliero-Universitaria S. Orsola Malpighi
City
Bologna
ZIP/Postal Code
40100
Country
Italy
Facility Name
Ospedale SS. Annunziata
City
Chieti
Country
Italy
Facility Name
Fondazione IRCCS Policlinico
City
Milano
Country
Italy
Facility Name
Policlinico
City
Napoli
ZIP/Postal Code
80100
Country
Italy
Facility Name
Policlinico Federico II
City
Napoli
Country
Italy
Facility Name
Azienda Ospedaliera di Padova
City
Padova
Country
Italy
Facility Name
Fondazione IRCCS Policlinico S. Matteo
City
Pavia
Country
Italy
Facility Name
U.O. Gastroenterologia Universitaria
City
Pisa
Country
Italy
Facility Name
Policlinico Universitario Campus Biomedico
City
Roma
ZIP/Postal Code
00128
Country
Italy
Facility Name
A.O. San Camillo-Forlanini
City
Roma
Country
Italy
Facility Name
Ospedale Sant'Andrea
City
Roma
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27144627
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.
Results Reference
background
PubMed Identifier
27144620
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.
Results Reference
background
PubMed Identifier
19457422
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.
Results Reference
background
PubMed Identifier
18694443
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.
Results Reference
background
PubMed Identifier
19174795
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.
Results Reference
background
PubMed Identifier
25970536
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.
Results Reference
background
PubMed Identifier
21820992
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.
Results Reference
background
PubMed Identifier
24310267
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.
Results Reference
background
PubMed Identifier
22730468
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.
Results Reference
background
PubMed Identifier
19091823
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.
Results Reference
background

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

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