A Novel Formulation of Bifidobacterium Longum BB536 and Lactobacillus Rhamnosus HN001 With Vitamin B6 on IBS Patients

NCT03815617 | Completed Phase 3

• 1 other identifier: 4651
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Irritable Bowel Syndrome

Keywords

IBS

Outcome Measures

Primary Outcomes (8)

• Visual Analogue Scale, ranging from 0 to 100

  For assessing abdominal pain and bloating

  Baseline

• Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS)

  Developed by Francis et al. (1997), and categorized as follows: remission (score \<75), mild (75-175), moderate (175-300) and severe (\>300).

  Baseline

• Bristol Stool Form Scale (BSFS)

  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)

  Baseline

• MEDSTYLE questionnaire

  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).

  Baseline

• Intestinal permeability

  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.

  Baseline

• Cultivable intestinal microbiota

  It was evaluated by faecal samples (5 g) were mixed with 45 mL sterilized physiological solution and homogenized.

  Baseline

• Community level catabolic profiles

  Biolog Eco microplates (Biolog, Inc., Hayward, CA, USA) were used to estimate the microbial diversity.

  Baseline

• Fecal metabolome

  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.

  Baseline

Study Arms (2)

Probiotic

ACTIVE COMPARATOR

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.

Dietary Supplement: Zircombi

Placebo

PLACEBO COMPARATOR

Same appearance of probiotic.

Dietary Supplement: Placebo

Interventions

Zircombi DIETARY_SUPPLEMENT

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.

Probiotic

Placebo DIETARY_SUPPLEMENT

Given as comparable packets. Same duration.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of IBS according to Rome IV Criteria

You may not qualify if:

• Diagnosis of structural abnormality of the GI tract
• Inflammatory bowel disorders
• Biliary duct obstructions
• Gallstones
• Abdominal surgery within the previous six months
• Infective diseases
• Drug or alcohol abuse
• Metabolic disturbances
• Mental illness
• Concomitant immunological, haematological or neoplastic disease
• Severe hepatic insufficiency (i.e., Child-Pugh class C)
• Severe heart failure (NYHA class III-IV)

Sponsors & Collaborators

• University of Bari: lead

Study Sites (1)

Clinica Medica "A. Murri", Department of Biomedical Sciences & Human Oncology, University of Bari Medical School

Bari, BA, 70124, Italy

Location

Related Publications (13)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 11984534 BACKGROUND

• 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.

  PMID: 15080847 BACKGROUND

• 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.

  PMID: 24912386 BACKGROUND

• Markowiak P, Slizewska K. Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients. 2017 Sep 15;9(9):1021. doi: 10.3390/nu9091021.

  PMID: 28914794 BACKGROUND

• 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.

  PMID: 26506949 BACKGROUND

• 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.

  PMID: 17056678 BACKGROUND

• 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.

  PMID: 26420851 BACKGROUND

• 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.

  PMID: 24830455 BACKGROUND

• 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.

  PMID: 28487606 BACKGROUND

MeSH Terms

Conditions

Irritable Bowel Syndrome

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• Piero Portincasa

  Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: January 22, 2019
• First Posted: January 24, 2019
• Study Start: February 1, 2017
• Primary Completion: May 31, 2018
• Study Completion: December 31, 2018
• Last Updated: January 24, 2019

Record last verified: 2019-01

Locations

IT (1)