<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03815617</url>
  </required_header>
  <id_info>
    <org_study_id>4651</org_study_id>
    <nct_id>NCT03815617</nct_id>
  </id_info>
  <brief_title>A Novel Formulation of Bifidobacterium Longum BB536 and Lactobacillus Rhamnosus HN001 With Vitamin B6 on IBS Patients</brief_title>
  <acronym>LLB</acronym>
  <official_title>The Beneficial Effects of a Novel Formulation of Bifidobacterium Longum BB536 and Lactobacillus Rhamnosus HN001 With Vitamin B6 on Gut Microbiota and Intestinal Permeability in IBS Patients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Bari</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Bari</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Irritable bowel syndrome (IBS) is one of the most frequent functional gastrointestinal&#xD;
      disorder with a prevalence ranging from 10 to 15 percent. IBS results from an interaction&#xD;
      among several factors, including genetic predisposition, gastrointestinal motility, visceral&#xD;
      hypersensitivity, immune activation with minimal inflammation, alterations in intestinal&#xD;
      microbiota, increased intestinal permeability, and food sensitivity. Of note, the management&#xD;
      of patients with IBS is critical. Since quantitative and qualitative disturbances of&#xD;
      intestinal microbiota can occur in IBS, interesting data support the use of probiotics to&#xD;
      modulate intestinal microbiota. The present study aimed to investigate the effects of a novel&#xD;
      formulation of B. longum BB536 and L. rhamnosus HN001 with vitamin B6 on the gut microbiota&#xD;
      and intestinal permeability in IBS subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Irritable bowel syndrome (IBS) is one of the most frequent functional gastrointestinal&#xD;
      disorder with a prevalence ranging from 10 to 15 percent. It is characterized by recurrent&#xD;
      chronic abdominal pain or discomfort in the absence of detectable organic causes with two or&#xD;
      more of the following conditions: onset associated with a change in frequency of stool, onset&#xD;
      associated with a change in form (appearance) of stool, or improvement with defecation.&#xD;
&#xD;
      IBS results from an interaction among several factors, including genetic predisposition,&#xD;
      gastrointestinal motility, visceral hypersensitivity, immune activation with minimal&#xD;
      inflammation, alterations in intestinal microbiota, increased intestinal permeability, and&#xD;
      food sensitivity.&#xD;
&#xD;
      IBS is associated with a high economic burden for the health care costs and work absenteeism.&#xD;
&#xD;
      The disease course is represented by unchanged symptoms in 30 to 50 percent or progression of&#xD;
      symptoms in 2 to 18 percent. On the other hand, an improvement in symptoms was recorded in 12&#xD;
      to 38 percent of patients.&#xD;
&#xD;
      Of note, the management of patients with IBS is critical. Several therapeutic options have&#xD;
      been proposed looking to the underlying pathophysiological mechanisms (i.e., dietary&#xD;
      modification, osmotic laxatives, lubiprostone, guanylate cyclase agonists,&#xD;
      5-hydroxytryptamine (serotonin) 4 receptor agonists, antidiarrheal agents, bile acid&#xD;
      sequestrants, 5-hydroxytryptamine (serotonin) 3 receptor antagonists, antispasmodic agents,&#xD;
      antidepressants, antibiotics, probiotics, behavior modification, anxiolytics, mast cell&#xD;
      stabilizer, and fecal transplantation).&#xD;
&#xD;
      Since quantitative and qualitative disturbances of intestinal microbiota can occur in IBS,&#xD;
      interesting data support the use of probiotics to modulate intestinal microbiota. The genus&#xD;
      Bifidobacterium is one of the most representative member of the intestinal microbiota with&#xD;
      large effects on overall gut physiology. Its metabolic activity results from the degradation&#xD;
      of oligo-fructose, production of acetate, and promotion of butyrate production by means of&#xD;
      cross-feeding. In particular, B. longum has beneficial effects on the immune system, and can&#xD;
      be considered a promising candidate for prevention/treatment of immune-mediated inflammatory&#xD;
      diseases.&#xD;
&#xD;
      The combination of specific bacterial strains of Lactobacillus with Bifidobacterium species&#xD;
      plays an interesting role in reserving the intestinal dysbiosis. The synergic action results&#xD;
      in survival on adverse gastrointestinal conditions, adhesion to intestinal mucosa,&#xD;
      immunomodulatory activities, and restoration of gut environment.&#xD;
&#xD;
      The present study aimed to investigate the effects of a novel formulation of B. longum BB536&#xD;
      and L. rhamnosus HN001 with vitamin B6 on the gut microbiota and intestinal permeability in&#xD;
      IBS subjects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2017</start_date>
  <completion_date type="Actual">December 31, 2018</completion_date>
  <primary_completion_date type="Actual">May 31, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Patients entered the following program:&#xD;
A run-in period of one month when symptoms, intestinal permeability, intestinal microbiota, and dietary evaluations were performed;&#xD;
Phase 1: randomization to treatment or placebo lasting 30 days;&#xD;
Wash-out period lasting 15 days, at the end of which symptoms were assessed;&#xD;
Phase 2: switch to next treatment in a crossover fashion. Treatment lasted for 30 days and at the end symptoms, intestinal permeability, and intestinal microbiota were evaluated again.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Visual Analogue Scale, ranging from 0 to 100</measure>
    <time_frame>Baseline</time_frame>
    <description>For assessing abdominal pain and bloating</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS)</measure>
    <time_frame>Baseline</time_frame>
    <description>Developed by Francis et al. (1997), and categorized as follows: remission (score &lt;75), mild (75-175), moderate (175-300) and severe (&gt;300).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Bristol Stool Form Scale (BSFS)</measure>
    <time_frame>Baseline</time_frame>
    <description>To assess bowel movements, consisting of a self-report instrument for classifying stool form into seven types ranging from &quot;separate hard lumps like nuts&quot; (type 1) to &quot;watery, no solid pieces&quot; (type 7)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MEDSTYLE questionnaire</measure>
    <time_frame>Baseline</time_frame>
    <description>A custom-designed questionnaire, tested across different ages, and anthropometric groups in health and disease, to measure anthropometric data, medical history, lifestyle and daily intake of foods. Frequency (day, week or month) and portion sizes (small, medium and large, represented by color pictures) of food consumption were estimated by using 35 food items (156 foods).The adherence to a Mediterranean diet was calculated by analyzing nine food categories with a score ranging from 0 point (lowest adherence) to 18 points (highest adherence).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Intestinal permeability</measure>
    <time_frame>Baseline</time_frame>
    <description>It was assessed by oral administration of four sugar probes, which selectively characterize the permeability from different tracts of the gastrointestinal system. Sucrose (SO) was used as a marker of gastro-duodenal permeability; lactulose (LA) and mannitol (MA) were used as markers of small intestine permeability also as (LA/MA), and sucralose (SU) as marker of&#xD;
8 colonic permeability.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cultivable intestinal microbiota</measure>
    <time_frame>Baseline</time_frame>
    <description>It was evaluated by faecal samples (5 g) were mixed with 45 mL sterilized physiological solution and homogenized.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Community level catabolic profiles</measure>
    <time_frame>Baseline</time_frame>
    <description>Biolog Eco microplates (Biolog, Inc., Hayward, CA, USA) were used to estimate the microbial diversity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fecal metabolome</measure>
    <time_frame>Baseline</time_frame>
    <description>Three grams of fecal sample were placed into 10 mL glass vials and added with 10 μL of 4-methyl- 2-pentanol (final concentration of 33 mg/L) as the internal standard.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Irritable Bowel Syndrome</condition>
  <arm_group>
    <arm_group_label>Probiotic</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The study design is a crossover randomized double-blind two-block placebo-controlled single center trial with an allocation ratio of 1:1 conducted between February 2017 and May 2018. Subjects are randomized at baseline visit to receive Block 1 (Zircombi 3 g, containing Bifidobacterium longum BB536 four billion CFU, Lactobacillus rhamnosus HN001 one billion CFU with B6 vitamin 1.4 mg) and Block 2 (placebo: maltodextrins, corn starch, silicon dioxide) depending on the randomization sequence. Subjects received one sachet pack daily containing placebo or probiotic. The active treatment was undistinguishable from placebo by physical and organoleptic characteristics. Participants in the study followed a free diet.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Same appearance of probiotic.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Zircombi</intervention_name>
    <description>Twenty-five IBS patients (Rome IV criteria) (M:F= 8:17; age 48 yrs ± 11 SD) were enrolled and randomized to treatment or placebo in a a crossover randomized double-blind two-block placebo-controlled trial. Abdominal pain and bloating, intestinal habits, severity of disease, intestinal permeability, and intestinal microbiota were performed at the different time points.</description>
    <arm_group_label>Probiotic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Given as comparable packets. Same duration.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of IBS according to Rome IV Criteria&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of structural abnormality of the GI tract&#xD;
&#xD;
          -  Inflammatory bowel disorders&#xD;
&#xD;
          -  Biliary duct obstructions&#xD;
&#xD;
          -  Gallstones&#xD;
&#xD;
          -  Abdominal surgery within the previous six months&#xD;
&#xD;
          -  Infective diseases&#xD;
&#xD;
          -  Drug or alcohol abuse&#xD;
&#xD;
          -  Metabolic disturbances&#xD;
&#xD;
          -  Mental illness&#xD;
&#xD;
          -  Concomitant immunological, haematological or neoplastic disease&#xD;
&#xD;
          -  Severe hepatic insufficiency (i.e., Child-Pugh class C)&#xD;
&#xD;
          -  Severe heart failure (NYHA class III-IV)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Piero Portincasa</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinica Medica &quot;A. Murri&quot;, Department of Biomedical Sciences &amp; Human Oncology, University of Bari Medical School</name>
      <address>
        <city>Bari</city>
        <state>BA</state>
        <zip>70124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012 Jul;10(7):712-721.e4. doi: 10.1016/j.cgh.2012.02.029. Epub 2012 Mar 15.</citation>
    <PMID>22426087</PMID>
  </reference>
  <reference>
    <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>
    <PMID>27144627</PMID>
  </reference>
  <reference>
    <citation>Bonfrate L, Tack J, Grattagliano I, Cuomo R, Portincasa P. Microbiota in health and irritable bowel syndrome: current knowledge, perspectives and therapeutic options. Scand J Gastroenterol. 2013 Sep;48(9):995-1009. doi: 10.3109/00365521.2013.799220.</citation>
    <PMID>23964766</PMID>
  </reference>
  <reference>
    <citation>Camilleri M. Peripheral mechanisms in irritable bowel syndrome. N Engl J Med. 2012 Oct 25;367(17):1626-35. doi: 10.1056/NEJMra1207068. No abstract available.</citation>
    <PMID>23094724</PMID>
  </reference>
  <reference>
    <citation>Sandler RS, Everhart JE, Donowitz M, Adams E, Cronin K, Goodman C, Gemmen E, Shah S, Avdic A, Rubin R. The burden of selected digestive diseases in the United States. Gastroenterology. 2002 May;122(5):1500-11. doi: 10.1053/gast.2002.32978.</citation>
    <PMID>11984534</PMID>
  </reference>
  <reference>
    <citation>El-Serag HB, Pilgrim P, Schoenfeld P. Systemic review: Natural history of irritable bowel syndrome. Aliment Pharmacol Ther. 2004 Apr 15;19(8):861-70. doi: 10.1111/j.1365-2036.2004.01929.x.</citation>
    <PMID>15080847</PMID>
  </reference>
  <reference>
    <citation>Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014 Aug;11(8):506-14. doi: 10.1038/nrgastro.2014.66. Epub 2014 Jun 10.</citation>
    <PMID>24912386</PMID>
  </reference>
  <reference>
    <citation>Markowiak P, Slizewska K. Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients. 2017 Sep 15;9(9):1021. doi: 10.3390/nu9091021.</citation>
    <PMID>28914794</PMID>
  </reference>
  <reference>
    <citation>Milani C, Lugli GA, Duranti S, Turroni F, Mancabelli L, Ferrario C, Mangifesta M, Hevia A, Viappiani A, Scholz M, Arioli S, Sanchez B, Lane J, Ward DV, Hickey R, Mora D, Segata N, Margolles A, van Sinderen D, Ventura M. Bifidobacteria exhibit social behavior through carbohydrate resource sharing in the gut. Sci Rep. 2015 Oct 28;5:15782. doi: 10.1038/srep15782.</citation>
    <PMID>26506949</PMID>
  </reference>
  <reference>
    <citation>Falony G, Vlachou A, Verbrugghe K, De Vuyst L. Cross-feeding between Bifidobacterium longum BB536 and acetate-converting, butyrate-producing colon bacteria during growth on oligofructose. Appl Environ Microbiol. 2006 Dec;72(12):7835-41. doi: 10.1128/AEM.01296-06. Epub 2006 Oct 20.</citation>
    <PMID>17056678</PMID>
  </reference>
  <reference>
    <citation>Rios-Covian D, Gueimonde M, Duncan SH, Flint HJ, de los Reyes-Gavilan CG. Enhanced butyrate formation by cross-feeding between Faecalibacterium prausnitzii and Bifidobacterium adolescentis. FEMS Microbiol Lett. 2015 Nov;362(21):fnv176. doi: 10.1093/femsle/fnv176. Epub 2015 Sep 28.</citation>
    <PMID>26420851</PMID>
  </reference>
  <reference>
    <citation>Khailova L, Petrie B, Baird CH, Dominguez Rieg JA, Wischmeyer PE. Lactobacillus rhamnosus GG and Bifidobacterium longum attenuate lung injury and inflammatory response in experimental sepsis. PLoS One. 2014 May 15;9(5):e97861. doi: 10.1371/journal.pone.0097861. eCollection 2014.</citation>
    <PMID>24830455</PMID>
  </reference>
  <reference>
    <citation>Toscano M, De Grandi R, Stronati L, De Vecchi E, Drago L. Effect of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 on the healthy gut microbiota composition at phyla and species level: A preliminary study. World J Gastroenterol. 2017 Apr 21;23(15):2696-2704. doi: 10.3748/wjg.v23.i15.2696.</citation>
    <PMID>28487606</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 22, 2019</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>January 23, 2019</last_update_submitted>
  <last_update_submitted_qc>January 23, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 24, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Bari</investigator_affiliation>
    <investigator_full_name>piero portincasa</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>IBS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irritable Bowel Syndrome</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03815617
org study id: 4651
nct id: NCT03815617
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Irritable bowel syndrome (IBS) is one of the most frequent functional gastrointestinal
      disorder with a prevalence ranging from 10 to 15 percent. IBS results from an interaction
      among several factors, including genetic predisposition, gastrointestinal motility, visceral
      hypersensitivity, immune activation with minimal inflammation, alterations in intestinal
      microbiota, increased intestinal permeability, and food sensitivity. Of note, the management
      of patients with IBS is critical. Since quantitative and qualitative disturbances of
      intestinal microbiota can occur in IBS, interesting data support the use of probiotics to
      modulate intestinal microbiota. The present study aimed to investigate the effects of a novel
      formulation of B. longum BB536 and L. rhamnosus HN001 with vitamin B6 on the gut microbiota
      and intestinal permeability in IBS subjects.
Irritable bowel syndrome (IBS) is one of the most frequent functional gastrointestinal
      disorder with a prevalence ranging from 10 to 15 percent. It is characterized by recurrent
      chronic abdominal pain or discomfort in the absence of detectable organic causes with two or
      more of the following conditions: onset associated with a change in frequency of stool, onset
      associated with a change in form (appearance) of stool, or improvement with defecation.

      IBS results from an interaction among several factors, including genetic predisposition,
      gastrointestinal motility, visceral hypersensitivity, immune activation with minimal
      inflammation, alterations in intestinal microbiota, increased intestinal permeability, and
      food sensitivity.

      IBS is associated with a high economic burden for the health care costs and work absenteeism.

      The disease course is represented by unchanged symptoms in 30 to 50 percent or progression of
      symptoms in 2 to 18 percent. On the other hand, an improvement in symptoms was recorded in 12
      to 38 percent of patients.

      Of note, the management of patients with IBS is critical. Several therapeutic options have
      been proposed looking to the underlying pathophysiological mechanisms (i.e., dietary
      modification, osmotic laxatives, lubiprostone, guanylate cyclase agonists,
      5-hydroxytryptamine (serotonin) 4 receptor agonists, antidiarrheal agents, bile acid
      sequestrants, 5-hydroxytryptamine (serotonin) 3 receptor antagonists, antispasmodic agents,
      antidepressants, antibiotics, probiotics, behavior modification, anxiolytics, mast cell
      stabilizer, and fecal transplantation).

      Since quantitative and qualitative disturbances of intestinal microbiota can occur in IBS,
      interesting data support the use of probiotics to modulate intestinal microbiota. The genus
      Bifidobacterium is one of the most representative member of the intestinal microbiota with
      large effects on overall gut physiology. Its metabolic activity results from the degradation
      of oligo-fructose, production of acetate, and promotion of butyrate production by means of
      cross-feeding. In particular, B. longum has beneficial effects on the immune system, and can
      be considered a promising candidate for prevention/treatment of immune-mediated inflammatory
      diseases.

      The combination of specific bacterial strains of Lactobacillus with Bifidobacterium species
      plays an interesting role in reserving the intestinal dysbiosis. The synergic action results
      in survival on adverse gastrointestinal conditions, adhesion to intestinal mucosa,
      immunomodulatory activities, and restoration of gut environment.

      The present study aimed to investigate the effects of a novel formulation of B. longum BB536
      and L. rhamnosus HN001 with vitamin B6 on the gut microbiota and intestinal permeability in
      IBS subjects.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Patients entered the following program:
A run-in period of one month when symptoms, intestinal permeability, intestinal microbiota, and dietary evaluations were performed;
Phase 1: randomization to treatment or placebo lasting 30 days;
Wash-out period lasting 15 days, at the end of which symptoms were assessed;
Phase 2: switch to next treatment in a crossover fashion. Treatment lasted for 30 days and at the end symptoms, intestinal permeability, and intestinal microbiota were evaluated again.
primary purpose: Treatment
masking: None (Open Label)
measure: Visual Analogue Scale, ranging from 0 to 100
time frame: Baseline
description: For assessing abdominal pain and bloating
measure: Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS)
time frame: Baseline
description: Developed by Francis et al. (1997), and categorized as follows: remission (score <75), mild (75-175), moderate (175-300) and severe (>300).
measure: Bristol Stool Form Scale (BSFS)
time frame: Baseline
description: To assess bowel movements, consisting of a self-report instrument for classifying stool form into seven types ranging from "separate hard lumps like nuts" (type 1) to "watery, no solid pieces" (type 7)
measure: MEDSTYLE questionnaire
time frame: Baseline
description: A custom-designed questionnaire, tested across different ages, and anthropometric groups in health and disease, to measure anthropometric data, medical history, lifestyle and daily intake of foods. Frequency (day, week or month) and portion sizes (small, medium and large, represented by color pictures) of food consumption were estimated by using 35 food items (156 foods).The adherence to a Mediterranean diet was calculated by analyzing nine food categories with a score ranging from 0 point (lowest adherence) to 18 points (highest adherence).
measure: Intestinal permeability
time frame: Baseline
description: It was assessed by oral administration of four sugar probes, which selectively characterize the permeability from different tracts of the gastrointestinal system. Sucrose (SO) was used as a marker of gastro-duodenal permeability; lactulose (LA) and mannitol (MA) were used as markers of small intestine permeability also as (LA/MA), and sucralose (SU) as marker of
8 colonic permeability.
measure: Cultivable intestinal microbiota
time frame: Baseline
description: It was evaluated by faecal samples (5 g) were mixed with 45 mL sterilized physiological solution and homogenized.
measure: Community level catabolic profiles
time frame: Baseline
description: Biolog Eco microplates (Biolog, Inc., Hayward, CA, USA) were used to estimate the microbial diversity.
measure: Fecal metabolome
time frame: Baseline
description: Three grams of fecal sample were placed into 10 mL glass vials and added with 10 μL of 4-methyl- 2-pentanol (final concentration of 33 mg/L) as the internal standard.
arm group label: Probiotic
arm group type: Active Comparator
description: The study design is a crossover randomized double-blind two-block placebo-controlled single center trial with an allocation ratio of 1:1 conducted between February 2017 and May 2018. Subjects are randomized at baseline visit to receive Block 1 (Zircombi 3 g, containing Bifidobacterium longum BB536 four billion CFU, Lactobacillus rhamnosus HN001 one billion CFU with B6 vitamin 1.4 mg) and Block 2 (placebo: maltodextrins, corn starch, silicon dioxide) depending on the randomization sequence. Subjects received one sachet pack daily containing placebo or probiotic. The active treatment was undistinguishable from placebo by physical and organoleptic characteristics. Participants in the study followed a free diet.
arm group label: Placebo
arm group type: Placebo Comparator
description: Same appearance of probiotic.
intervention type: Dietary Supplement
intervention name: Zircombi
description: Twenty-five IBS patients (Rome IV criteria) (M:F= 8:17; age 48 yrs ± 11 SD) were enrolled and randomized to treatment or placebo in a a crossover randomized double-blind two-block placebo-controlled trial. Abdominal pain and bloating, intestinal habits, severity of disease, intestinal permeability, and intestinal microbiota were performed at the different time points.
arm group label: Probiotic
intervention type: Dietary Supplement
intervention name: Placebo
description: Given as comparable packets. Same duration.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Piero Portincasa
role: Principal Investigator
affiliation: Professor
facility: 
country: Italy
citation: Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012 Jul;10(7):712-721.e4. doi: 10.1016/j.cgh.2012.02.029. Epub 2012 Mar 15.
PMID: 22426087
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.
PMID: 27144627
citation: Bonfrate L, Tack J, Grattagliano I, Cuomo R, Portincasa P. Microbiota in health and irritable bowel syndrome: current knowledge, perspectives and therapeutic options. Scand J Gastroenterol. 2013 Sep;48(9):995-1009. doi: 10.3109/00365521.2013.799220.
PMID: 23964766
citation: Camilleri M. Peripheral mechanisms in irritable bowel syndrome. N Engl J Med. 2012 Oct 25;367(17):1626-35. doi: 10.1056/NEJMra1207068. No abstract available.
PMID: 23094724
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responsible party type: Principal Investigator
investigator affiliation: University of Bari
investigator full name: piero portincasa
investigator title: Principal Investigator
mesh term: Irritable Bowel Syndrome