- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02204891
Probiotics in Intestinal Bacterial Overgrowth
A Clinical Study of the Efficacy of a Formulation of Four Probiotics in Patients With Syndrome of Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder. Pathogenesis remains multifactorial. Better understanding of the interaction of the host with intestinal microbiota the last decade led to the knowledge that many of the symptoms of IBS, mainly bloating and diarrhea, are related with the overgrowth of bacteria of colonic type in the small intestine. This overgrowth frames the syndrome of intestinal bacterial overgrowth (SIBO) where colonic type of bacteria predominate in the proximal parts of the small intestine. Fermentation of dietary carbohydrates by the bacteria colonizers of SIBO ends with the over-production of gas generating thus symptoms of IBS. The relationship between IBS and SIBO was found by a series of prospective observational studies using the lactulose and the glucose tolerance tests for the diagnosis of SIBO. Using this test, the prevalence of SIBO in patients with IBS ranged between 65 and 85%. The gold-standard technique for the diagnosis of SIBO is the quantitative culture of the content of the proximal intestine i.e. of the duodenum after upper GI tract endoscopy. Few studies are available with this design and they suggest a growth of colonic type of flora at counts equal to or greater than 10^5 cfu/ml as diagnostic of SIBO. Based on systematic review of the literature but also on data generated in a cohort of 320 consecutive patients undergoing upper GI tract endoscopy, normal subjects are never greater than 10^3 cfu/m in the duodenum. In the latter publication coming from Athens, using variable cut-offs greater than 10^3 or 10^4 or 10^5 cfu/ml for the diagnosis of SIBO, the frequency of SIBO was significantly greater among sufferers than among non-sufferers from IBS.
Oral supplementation with probiotics may be a rational approach for the eradication of SIBO and subsequently of the symptoms of IBS. The majority of probiotic bacteria belong to the Lactobacillus and Bifidobacterium genera. They are Gram-positive lactic acid-producing bacteria that constitute a major part of the normal intestinal microflora in animals and humans. The rationale behind their use as a therapeutic strategy in IBS is that orally administered probiotics may replace the overgrown enteric-type bacteria of SIBO. Four randomized clinical trials are available evaluating the efficacy of orally administered probiotics in IBS. The common findings of these trials are that a) efficacy refers to the improvement of symptoms of bloating and of diarrhea that are typical symptoms of the presence of SIBO; and b) efficacy is usually found when mixtures of different species of probiotics are used. However, no study has ever tested the efficacy of probiotics in patients with IBS and SIBO proven by small intestinal culture.
The aim of the present study is to demonstrate the effect of a mixture of four species of probiotics (Saccharomyces boulardii, Bifidobacterium lactis BB-12, Lactobacillus acidophilus LA-5 and Lactobacillus plantarum) in patients with symptomatic IBS who have culture verified SIBO and those who do not have. This will provide direct evidence for the role of probiotics in treating part of the pathogenesis of IBS.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Attiki
-
Athens, Attiki, Greece, 12462
- Department of Gastroenterology, ATTIKON University Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥18 years
- Both genders
- Written informed consent by study participants
- Presence of IBS according to Rome III criteria
- Equal number of SIBO-positive and SIBO-negative patients
Exclusion Criteria:
- Age <18 years
- Deny to consent
- Pregnancy or lactation
- Presence of inflammatory bowel disease
- Presence of acute GI tract infection
- Diabetes mellitus type 1 or type 2
- Use of laxatives and antibiotics within the preceding 6 weeks
- Presence of fever, abdominal mass, signs of bowel obstruction and/or leucocytosis
- Abnormal serum levels of thyroid -stimulating hormone.
- History of colon cancer or diverticulitis
- Infection by human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus
- Patients with celiac disease defined by biopsy of the duodenal mucosa.
- History of scleroderma and gastroparesis
- Pregnancy or planning pregnancy the next 3 months
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Probiotics in SIBO
Administration of probiotics in patients with IBS and SIBO
|
Mixture of the four probiotics in one capsule.
One capsule twice daily for 30 days
Other Names:
|
Active Comparator: Probiotics
Administration of probiotics in patients with IBS without SIBO
|
One capsule twice daily for 30 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
• The efficacy of probiotics in improvement of symptoms of IBS in patients with SIBO compared to their efficacy in patients with IBS without SIBO.
Time Frame: 30 days
|
This will be assessed after 30 days from start of therapy (visit 2) by comparisons of grading of symptoms and results of OLT between the two groups of treatment.
|
30 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
• The efficacy of probiotics in symptoms of IBS in patients with SIBO compared to their efficacy in patients with IBS without SIBO.
Time Frame: 60 days
|
This will be assessed after 60 days from start of therapy (visit 3) by comparisons of grading of symptoms and results of OLT between the two groups of treatment.
|
60 days
|
The efficacy of probiotics in specific symptoms of IBS both visits 2 and 3.
Time Frame: Days 30 and 60
|
This will be done by comparing the grading for every symptom of IBS of patients in visits 2 and 3 compared with the baseline visit 1.
|
Days 30 and 60
|
• The importance of the inflammation cascade in the pathogenesis of SIBO-related IBS.
Time Frame: 30 days
|
This will be done by comparing the duodenal aspirate cytokines of the two groups of treatment.
|
30 days
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Konstantinos Triantafyllou, MD, PhD, University of Athens, Medical School
- Principal Investigator: Evangelos Giamarellos-Bourboulis, MD, PhD, University of Athens, Medical School
Publications and helpful links
General Publications
- Pyleris E, Giamarellos-Bourboulis EJ, Tzivras D, Koussoulas V, Barbatzas C, Pimentel M. The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Dig Dis Sci. 2012 May;57(5):1321-9. doi: 10.1007/s10620-012-2033-7. Epub 2012 Jan 20.
- Choi CH, Jo SY, Park HJ, Chang SK, Byeon JS, Myung SJ. A randomized, double-blind, placebo-controlled multicenter trial of saccharomyces boulardii in irritable bowel syndrome: effect on quality of life. J Clin Gastroenterol. 2011 Sep;45(8):679-83. doi: 10.1097/MCG.0b013e318204593e. Erratum In: J Clin Gastroenterol. 2011 Oct;45(9):838.
- Ringel-Kulka T, Palsson OS, Maier D, Carroll I, Galanko JA, Leyer G, Ringel Y. Probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 versus placebo for the symptoms of bloating in patients with functional bowel disorders: a double-blind study. J Clin Gastroenterol. 2011 Jul;45(6):518-25. doi: 10.1097/MCG.0b013e31820ca4d6.
- Ki Cha B, Mun Jung S, Hwan Choi C, Song ID, Woong Lee H, Joon Kim H, Hyuk J, Kyung Chang S, Kim K, Chung WS, Seo JG. The effect of a multispecies probiotic mixture on the symptoms and fecal microbiota in diarrhea-dominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Clin Gastroenterol. 2012 Mar;46(3):220-7. doi: 10.1097/MCG.0b013e31823712b1.
- Yoon JS, Sohn W, Lee OY, Lee SP, Lee KN, Jun DW, Lee HL, Yoon BC, Choi HS, Chung WS, Seo JG. Effect of multispecies probiotics on irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Gastroenterol Hepatol. 2014 Jan;29(1):52-9. doi: 10.1111/jgh.12322.
- Leventogiannis K, Gkolfakis P, Spithakis G, Tsatali A, Pistiki A, Sioulas A, Giamarellos-Bourboulis EJ, Triantafyllou K. Effect of a Preparation of Four Probiotics on Symptoms of Patients with Irritable Bowel Syndrome: Association with Intestinal Bacterial Overgrowth. Probiotics Antimicrob Proteins. 2019 Jun;11(2):627-634. doi: 10.1007/s12602-018-9401-3. Erratum In: Probiotics Antimicrob Proteins. 2018 Mar 28;:
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- LACTO01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Irritable Bowel Syndrome
-
ProgenaBiomeRecruitingIrritable Bowel Syndrome | Irritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Constipation | Irritable Bowel Syndrome Characterized by Constipation | Irritable Bowel Syndrome Mixed | Irritable Bowel Syndrome Without Diarrhea | Irritable Bowel | Irritable Bowel Syndrome Aggravated and other conditionsUnited States
-
ClasadoCR2O B.V.RecruitingIrritable Bowel Syndrome | Irritable Bowel Syndrome - Constipation | Irritable Bowel Syndrome - Diarrhoea | Irritable Bowel Syndrome - MixedBelgium, Netherlands, United Kingdom
-
Istanbul Medipol University HospitalTepecik Training and Research Hospital; Bozyaka Training and Research Hospital and other collaboratorsRecruitingIrritable Bowel Syndrome | Irritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Constipation | Irritable Bowel Syndrome MixedTurkey
-
Federal Stare Budgetary Scientific Institution,...I.M. Sechenov First Moscow State Medical University; RML INVEST, Torkhovsky...CompletedIrritable Bowel Syndrome | Irritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Constipation | Irritable Bowel Syndrome MixedRussian Federation
-
University of California, Los AngelesCompletedIrritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Mixed Bowel HabitsUnited States
-
University of ViennaCompleted
-
Thomayer University HospitalCharles University, Czech RepublicActive, not recruitingIrritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome MixedCzechia
-
Shahid Beheshti University of Medical SciencesCompletedIrritable Bowel DiseaseIran, Islamic Republic of
-
Universidad Autonoma de ChihuahuaNot yet recruitingIrritable Bowel Syndrome | Constipation-predominant Irritable Bowel Syndrome | Diarrhea- Irritable Bowel Syndrome
-
Vasily IsakovRussian Science Foundation; Azbuka vkusa; Federal Research Centre of Nutrition...CompletedIrritable Bowel Syndrome With Constipation | Constipation-predominant Irritable Bowel SyndromeRussian Federation
Clinical Trials on Probiotics in SIBO
-
AC Camargo Cancer CenterRecruitingAnal Cancer Squamous CellBrazil
-
University of TurkuUniversity of Michigan; The Forsyth InstituteCompleted
-
Rennes University HospitalTerminated
-
Chinese PLA General HospitalUnknownElderly | Small Intestinal Bacterial Overgrowth | Male | 16s rRNAChina
-
Glac Biotech Co., LtdCompletedMetabolic SyndromeTaiwan
-
University of TurkuWithdrawnDental CariesFinland
-
TCI Co., Ltd.Recruiting
-
University of Milano BicoccaCompleted
-
Arkansas Children's Hospital Research InstituteCompleted
-
Chr HansenAarhus University HospitalCompletedInfant Development | Gut MicrobiomeDenmark