Irritable Bowel SyndromeNCT02204891
Probiotics in Intestinal Bacterial Overgrowth
A study testing Probiotics in SIBO and Probiotics in people with Irritable Bowel Syndrome, run by University of Athens at 1 site in Greece.
Trial summary
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 irritable bowel syndrome (IBS) who have culture verified syndrome of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Irritable Bowel Syndrome
- What is being tested?
- Probiotics in SIBO and Probiotics
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteGreece
- Study dates
- Sep 2014to Sep 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Greece1 site
Department of Gastroenterology, ATTIKON University Hospital
Athens, Attica, 12462
About this study
Official title: A Clinical Study of the Efficacy of a Formulation of Four Probiotics in Patients With Syndrome of Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome
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 irritable bowel syndrome (IBS) who have culture verified syndrome of intestinal bacterial overgrowth (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.
Read the 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.
- Conditions
- Irritable Bowel Syndrome
- Being tested
- Probiotics in SIBO, Probiotics
- Keywords
- Abdominal pain, Abdominal discomfort, Flatulence, Diarrhea, Bacterial overgrowth, Cytokines
- Medical subject headings
- Irritable Bowel Syndrome, Abdominal Pain, Flatulence, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probiotics in SIBODietary supplement
Also called Saccharomyces Bifidobacterium Lactobacillus species
Mixture of the four probiotics in one capsule. One capsule twice daily for 30 days
ProbioticsDietary supplement
One capsule twice daily for 30 days
| Study group | Role | What they receive |
|---|---|---|
| Probiotics in SIBO | Experimental | Administration of probiotics in patients with IBS and SIBO Receives: Dietary Supplement: Probiotics in SIBO |
| Probiotics | Active comparator | Administration of probiotics in patients with IBS without SIBO Receives: Dietary Supplement: Probiotics |
What is being measured
The primary outcome is the main question the study is designed to answer.
• The efficacy of probiotics in improvement of symptoms of IBS in patients with SIBO compared to their efficacy in patients with IBS without SIBO.
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.
Measured: 30 days
Secondary outcomes (3)
• The efficacy of probiotics in symptoms of IBS in patients with SIBO compared to their efficacy in patients with IBS without SIBO.
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.
Measured: 60 days
The efficacy of probiotics in specific symptoms of IBS both visits 2 and 3.
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.
Measured: Days 30 and 60
• The importance of the inflammation cascade in the pathogenesis of SIBO-related IBS.
This will be done by comparing the duodenal aspirate cytokines of the two groups of treatment.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2014 (estimated)
- Study startSep 2014
- Primary completionJun 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Irritable Bowel SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Athens
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Evangelos J. Giamarellos-Bourboulis, M.D., University of Athens
- Investigators
- Konstantinos Triantafyllou, MD, PhD, Principal investigator, University of Athens, Medical SchoolEvangelos Giamarellos-Bourboulis, MD, PhD, Principal investigator, University of Athens, Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02204891
- Sponsor's protocol ID
- LACTO01
- Status last verified
- Mar 2017
- First submitted
- 28 Jul 2014
- Last updated
- 20 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
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.
PubMed 22262197Choi 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.
PubMed 21301358Ringel-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.
PubMed 21436726Ki 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.
PubMed 22157240Yoon 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.
PubMed 23829297Leventogiannis 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.
PubMed 29508268
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study of the Efficacy of a Formulation of Four Probiotics in Patients With Syndrome of Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome
- ClinicalTrials.gov ID
- NCT02204891
- Acronym / sponsor ID
- LACTO01
- Conditions
- Irritable Bowel Syndrome
- Keywords
- Abdominal pain, Abdominal discomfort, Flatulence, Diarrhea, Bacterial overgrowth, Cytokines
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of AthensUniversity, hospital or other
- Study start
- Sep 2014 (actual)
- Primary completion
- Jun 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 31 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 irritable bowel syndrome (IBS) who have culture verified syndrome of intestinal bacterial overgrowth (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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotics in SIBO | Experimental | Dietary Supplement: Probiotics in SIBOAdministration of probiotics in patients with IBS and SIBO |
| Probiotics | Active comparator | Dietary Supplement: ProbioticsAdministration of probiotics in patients with IBS without SIBO |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (14 listed)
- Age <18 years
- Deny to consent
- Pregnancy or lactation
- Presence of inflammatory bowel disease
- Presence of acute GI tract infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probiotics in SIBOAlso: Saccharomyces Bifidobacterium Lactobacillus speciesMixture of the four probiotics in one capsule. One capsule twice daily for 30 days | Dietary supplement | Probiotics in SIBO |
| ProbioticsOne capsule twice daily for 30 days | Dietary supplement | Probiotics |
Primary outcome
• 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.
3 secondary outcomes
• 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
The efficacy of probiotics in specific symptoms of IBS both visits 2 and 3.
Time frame: Days 30 and 60
• The importance of the inflammation cascade in the pathogenesis of SIBO-related IBS.
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2017.
- Background: PubMed 22262197Pyleris 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.
- Background: PubMed 21301358Choi 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.
- Background: PubMed 21436726Ringel-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.
- Background: PubMed 22157240Ki 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.
- Background: PubMed 23829297Yoon 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.
- Derived from this study: PubMed 29508268Leventogiannis 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Konstantinos Triantafyllou, MD, PhD principal investigator
University of Athens, Medical School
Evangelos Giamarellos-Bourboulis, MD, PhD principal investigator
University of Athens, Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotics in SIBO and Probiotics in people with Irritable Bowel Syndrome, run by University of Athens at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
• 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02204891, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2017; AzTrials last refreshed its copy on 31 Oct 2026.