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The Effect of Two Probiotic Products on the Intestinal Barrier Function in Patients With Irritable Bowel Syndrome

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ClinicalTrials.gov Identifier: NCT03986476
Recruitment Status : Recruiting
First Posted : June 14, 2019
Last Update Posted : June 14, 2019
Sponsor:
Information provided by (Responsible Party):
Robert Brummer, Örebro University, Sweden

Brief Summary:
This study will investigate the effects of supplementation with two different probiotic products (Lactobacillus reuteri strains) on the intestinal barrier function, gut health and stress symptoms in diarrhoea-predominant irritable bowel syndrome (IBS-D) patients.

Condition or disease Intervention/treatment Phase
IBS Dietary Supplement: Probiotics Other: Placebo Not Applicable

Detailed Description:
After having given their written informed consent, subjects will complete screening procedures to evaluate their eligibility for the study (visit 1). Study participants will undergo two baseline visits (visits 2 and 3, 3 weeks apart) to account for individual variations, and will then be randomly assigned to 6-week intake of one of two Lactobacillus reuteri strains, or placebo in a ratio of 1:1:1 (stratified by sex). Participants will attend a study visit three weeks into the intervention (visit 4) and at the end of the intervention (visit 5, week 6). The intestinal permeability will be assessed using a standardized multi-sugar test at visit 2, visit 3, visit 4, and at end of intervention (visit 5). Blood, saliva and faecal samples will be collected at visit 2-5. In addition, gastrointestinal symptoms will be recorded at those visits (using Gastrointestinal symptom rating scale-IBS, GSRS-IBS; IBS severity scoring system, IBS- SSS). Quality of life using the 5Q-5D-5L and Hospital Anxiety and Depression Scale (HADS) scores will also be recorded at those visits. In addition, at visit 3 and visit 5, the IBS-Quality of life (IBS-QoL) and the Perceived Stress Scale (PSS) will be completed. In a daily diary, participants will record stool frequency and consistency from visit 2 until end-of-study visit 5. Dietary habits of the patients will be assessed via a food frequency questionnaire (FFQ) and a 3-day food diary before the intervention (between visit 2 and 3).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Effect of Two Probiotic Products on the Intestinal Barrier Function in Patients With Irritable Bowel Syndrome
Actual Study Start Date : March 26, 2019
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2020

Arm Intervention/treatment
Experimental: Lactobacillus reuteri strain 1
Probiotic compound
Dietary Supplement: Probiotics
5x10^8 colony forming units (CFU) of each probiotic strain, two capsules per day over six weeks

Experimental: Lactobacillus reuteri strain 2
Probiotic compound
Dietary Supplement: Probiotics
5x10^8 colony forming units (CFU) of each probiotic strain, two capsules per day over six weeks

Placebo Comparator: Placebo
Placebo
Other: Placebo
Similar in shape and taste to intervention capsules but without the probiotic components, two capsules per day over six weeks




Primary Outcome Measures :
  1. Change in small intestinal permeability after 6 weeks (urinary lactulose/rhamnose ratio, 0-5h) [ Time Frame: 6 weeks ]
    Difference in small intestinal permeability, measured as the urinary lactulose/rhamnose secretion ratio (0-5h), after a 6-week intervention with the probiotic products compared to the placebo product


Secondary Outcome Measures :
  1. Change in small intestinal permeability after 3 weeks (urinary lactulose/rhamnose ratio, 0-5h) [ Time Frame: 3 weeks ]
    Difference in small intestinal permeability, measured as the urinary lactulose/rhamnose secretion ratio (0-5h), after a 3-week intervention with the probiotic products compared to the placebo product

  2. Change in whole gut permeability after 6 weeks (urinary sucralose/erythritol ratio, 0-24h) [ Time Frame: 6 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in whole gut permeability, measured as urinary sucralose/erythritol excretion ratio (0-24hrs)

  3. Change in whole gut permeability after 3 weeks (urinary sucralose/erythritol excretion ratio, 0-24h) [ Time Frame: 3 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in whole gut permeability, measured as urinary sucralose/erythritol excretion ratio (0-24hrs)

  4. Change in colonic permeability after 6 weeks (urinary sucralose/erythritol ratio, 5-24h) [ Time Frame: 6 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in colonic permeability, measured as urinary sucralose/erythritol ratio (5-24hrs)

  5. Change in colonic permeability after 3 weeks (urinary sucralose/erythritol ratio, 5-24hrs) [ Time Frame: 3 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in colonic permeability, measured as urinary sucralose/erythritol ratio (5-24hrs)

  6. Change in gastroduodenal permeability after 6 weeks (urinary sucrose excretion, 0-5hrs) [ Time Frame: 6 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in gastroduodenal permeability, measured as urinary sucrose excretion (0-5hrs)

  7. Change in gastroduodenal permeability after 3 weeks (urinary sucrose excretion, 0-5hrs) [ Time Frame: 3 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in gastroduodenal permeability, measured as urinary sucrose excretion (0-5hrs)

  8. Change in inflammatory status after 3 weeks [ Time Frame: 3 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in inflammatory markers in blood (e.g. high-sensitive C-reactive protein)

  9. Change in inflammatory status after 6 weeks [ Time Frame: 6 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in inflammatory markers in blood (e.g. high-sensitive C-reactive protein)


Other Outcome Measures:
  1. Change in stool frequency and consistency (daily diary on bowel movement using Bristol Stool Chart) [ Time Frame: 3 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in stool frequency and consistency

  2. Change in stool frequency and consistency (daily diary on bowel movement using Bristol Stool Chart) [ Time Frame: 6 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in stool frequency and consistency

  3. Change in gastrointestinal symptoms measured by the IBS-specific gastrointestinal symptom rating scale (GSRS-IBS) [ Time Frame: 3 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in gastrointestinal symptoms (GSRS-IBS total score range 0-3, 0-no symptoms, 3-extreme degree of symptoms)

  4. Change in gastrointestinal symptoms measured by the IBS symptom severity score (IBS-SSS) [ Time Frame: 3 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in gastrointestinal symptoms (IBS-SSS, total score range 0-500, 0-no symptoms, 500-extreme degree of symptoms)

  5. Change in gastrointestinal symptoms measured by the IBS-specific gastrointestinal symptom rating scale (GSRS-IBS) [ Time Frame: 6 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in gastrointestinal symptoms (GSRS-IBS total score range 0-3, 0-no symptoms, 3-extreme degree of symptoms)

  6. Change in gastrointestinal symptoms measured by the IBS symptom severity score (IBS-SSS) [ Time Frame: 6 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in gastrointestinal symptoms (IBS-SSS, total score range 0-500, 0-no symptoms, 500-extreme degree of symptoms)

  7. Change in quality of life measured by IBS-specific quality of life (IBS-QOL) questionnaire [ Time Frame: 3 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in quality of life (IBS-QOL total range, range: 0-100, 0-low quality of life, 100-high quality of life)

  8. Change in quality of life measured by IBS-specific quality of life (IBS-QOL) questionnaire [ Time Frame: 6 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in quality of life IBS-QOL total range, range: 0-100, 0-low quality of life, 100-high quality of life)

  9. Change in perceived stress using the perceived stress scale (PSS) [ Time Frame: 3 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in perceived stress (PSS range 0-40: 0-no stress, 40-high stress)

  10. Change in perceived stress using the perceived stress scale (PSS) [ Time Frame: 6 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in perceived stress (PSS range 0-40: 0-no stress, 40-high stress)

  11. Change in anxiety and depression symptoms using the Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 3 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in anxiety and depression symptoms (HADS range: 0 to 21 for anxiety and 0 to 21 for depression, 0-low levels, 21 high levels)

  12. Change in anxiety and depression symptoms using the Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 6 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in anxiety and depression symptoms (HADS range: 0 to 21 for anxiety and 0 to 21 for depression, 0-low levels, 21 high levels)

  13. Change in salivary cortisol levels [ Time Frame: 3 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in salivary cortisol levels

  14. Change in salivary cortisol levels [ Time Frame: 6 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in salivary cortisol levels

  15. Change in intestinal microbiota composition (16S rRNA-based next generation sequencing of faecal samples) after probiotic intervention [ Time Frame: 3 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in intestinal microbiota composition

  16. Change in intestinal microbiota composition (16S rRNA-based next generation sequencing of faecal samples) after probiotic intervention [ Time Frame: 6 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in intestinal microbiota composition

  17. Change in metabolomic profile in faecal samples after probiotic intervention [ Time Frame: 3 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in metabolomic profile in faecal samples

  18. Change in metabolomic profile in faecal samples after probiotic intervention [ Time Frame: 6 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in metabolomic profile in faecal samples

  19. Change in metabolomic profile in blood samples after probiotic intervention [ Time Frame: 3 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in metabolomic profile in faecal samples

  20. Change in metabolomic profile in blood samples after probiotic intervention [ Time Frame: 6 weeks ]
    Difference between intervention with the probiotic products compared to the placebo in metabolomic profile in faecal samples



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent
  • Fulfilled Rome IV diagnostic criteria for IBS with predominant diarrhoea
  • Mild-to-severe IBS symptoms according to the IBS severity scoring system (IBS-SSS; a score of ≥75)
  • Age: 18-65 years

Exclusion Criteria:

  1. Known organic gastrointestinal disease (e.g. inflammatory bowel disease, IBD)
  2. Previous abdominal surgery which might influence gastrointestinal function, except appendectomy and cholecystectomy
  3. History of or present gastrointestinal malignancy or polyposis
  4. Recently (within the last 6 months) diagnosed gastrointestinal infection
  5. Current diagnosis of dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation
  6. Chronic neurological/neurodegenerative diseases (e.g. Parkinson's disease, multiple sclerosis)
  7. Autoimmune disease and/or patients receiving immunosuppressive medications
  8. Chronic pain syndromes (e.g. fibromyalgia)
  9. Chronic fatigue syndrome
  10. Severe endometriosis
  11. Coeliac disease
  12. Recently (within the last 3 months) diagnosed lactose intolerance
  13. Females who are pregnant or breast-feeding
  14. Regular intake of systemic corticosteroids and anti-inflammatory medication (including non-steroidal anti-inflammatory drugs, NSAIDs) during the last 3 months or incidental use in the last 2 weeks prior to randomisation
  15. Recent (< 4 weeks) intake of proton pump inhibitors, PPIs (e.g., omeprazol)
  16. Use of anti-depressants in the last 3 months
  17. Regular oral intake of mast cell stabilising drugs (e.g. sodium cromoglycate) during the last 3 months or incidental use in the last 2 weeks prior to screening
  18. Antimicrobial treatment 6 weeks prior to first screening visit
  19. Antimicrobial prophylaxis (eg. acne, urinary tract infection)
  20. Regular consumption of probiotic products 4 weeks prior to first baseline visit
  21. Concurrent or recent (<4 weeks) use of nutritional supplements or herb products affecting intestinal function (e.g. aloe vera, St. John´s Wort, fibres, prebiotics) if the investigator considers those could affect the study outcome.
  22. Inability to maintain exercise routine and dietary pattern during the study.
  23. Abuse of alcohol or drugs
  24. Any clinically significant present or past disease/condition which in the investigator's opinion could interfere with the results of the trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03986476


Contacts
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Contact: Julia M König, PhD 0046 19 30 3645 julia.konig@oru.se
Contact: Robert J Brummer, MD, PhD 0046 19 30 3731 robert.brummer@oru.se

Locations
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Sweden
Örebro University Recruiting
Örebro, Örebro Län, Sweden, 70182
Contact: Julia M König, PhD         
Sponsors and Collaborators
Örebro University, Sweden
Investigators
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Principal Investigator: Robert J Brummer, MD, PhD Örebro University

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Responsible Party: Robert Brummer, Professor, MD, PhD, Örebro University, Sweden
ClinicalTrials.gov Identifier: NCT03986476     History of Changes
Other Study ID Numbers: 2018/450
First Posted: June 14, 2019    Key Record Dates
Last Update Posted: June 14, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No individual participant data will be shared, only data on group level will

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Irritable Bowel Syndrome
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases