Clinical trial NCT03986476: The Effect of Two Probiotic Products on the Intestinal Barrier Function in Patients With Irritable Bowel Syndrome
Official title: The Effect of Two Probiotic Products on the Intestinal Barrier Function in Patients With Irritable Bowel Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: IBS
Lead sponsor: Örebro University, Sweden
Sponsor class: OTHER
First posted: 2019-06-14
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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).

Eligibility 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

Primary outcomes:
measure: Change in small intestinal permeability after 6 weeks (urinary lactulose/rhamnose ratio, 0-5h)
timeFrame: 6 weeks
Secondary outcomes:
measure: Change in small intestinal permeability after 3 weeks (urinary lactulose/rhamnose ratio, 0-5h)
timeFrame: 3 weeks
measure: Change in whole gut permeability after 6 weeks (urinary sucralose/erythritol ratio, 0-24h)
timeFrame: 6 weeks
measure: Change in whole gut permeability after 3 weeks (urinary sucralose/erythritol excretion ratio, 0-24h)
timeFrame: 3 weeks
measure: Change in colonic permeability after 6 weeks (urinary sucralose/erythritol ratio, 5-24h)
timeFrame: 6 weeks
measure: Change in colonic permeability after 3 weeks (urinary sucralose/erythritol ratio, 5-24hrs)
timeFrame: 3 weeks
measure: Change in gastroduodenal permeability after 6 weeks (urinary sucrose excretion, 0-5hrs)
timeFrame: 6 weeks
measure: Change in gastroduodenal permeability after 3 weeks (urinary sucrose excretion, 0-5hrs)
timeFrame: 3 weeks
measure: Change in inflammatory status after 3 weeks
timeFrame: 3 weeks
measure: Change in inflammatory status after 6 weeks
timeFrame: 6 weeks
Other outcomes:
measure: Change in stool frequency and consistency (daily diary on bowel movement using Bristol Stool Chart)
timeFrame: 3 weeks
measure: Change in stool frequency and consistency (daily diary on bowel movement using Bristol Stool Chart)
timeFrame: 6 weeks
measure: Change in gastrointestinal symptoms measured by the IBS-specific gastrointestinal symptom rating scale (GSRS-IBS)
timeFrame: 3 weeks
measure: Change in gastrointestinal symptoms measured by the IBS symptom severity score (IBS-SSS)
timeFrame: 3 weeks
measure: Change in gastrointestinal symptoms measured by the IBS-specific gastrointestinal symptom rating scale (GSRS-IBS)
timeFrame: 6 weeks
measure: Change in gastrointestinal symptoms measured by the IBS symptom severity score (IBS-SSS)
timeFrame: 6 weeks
measure: Change in quality of life measured by IBS-specific quality of life (IBS-QOL) questionnaire
timeFrame: 3 weeks
measure: Change in quality of life measured by IBS-specific quality of life (IBS-QOL) questionnaire
timeFrame: 6 weeks
measure: Change in perceived stress using the perceived stress scale (PSS)
timeFrame: 3 weeks
measure: Change in perceived stress using the perceived stress scale (PSS)
timeFrame: 6 weeks
measure: Change in anxiety and depression symptoms using the Hospital Anxiety and Depression Scale (HADS)
timeFrame: 3 weeks
measure: Change in anxiety and depression symptoms using the Hospital Anxiety and Depression Scale (HADS)
timeFrame: 6 weeks
measure: Change in salivary cortisol levels
timeFrame: 3 weeks
measure: Change in salivary cortisol levels
timeFrame: 6 weeks
measure: Change in intestinal microbiota composition (16S rRNA-based next generation sequencing of faecal samples) after probiotic intervention
timeFrame: 3 weeks
measure: Change in intestinal microbiota composition (16S rRNA-based next generation sequencing of faecal samples) after probiotic intervention
timeFrame: 6 weeks
measure: Change in metabolomic profile in faecal samples after probiotic intervention
timeFrame: 3 weeks
measure: Change in metabolomic profile in faecal samples after probiotic intervention
timeFrame: 6 weeks
measure: Change in metabolomic profile in blood samples after probiotic intervention
timeFrame: 3 weeks
measure: Change in metabolomic profile in blood samples after probiotic intervention
timeFrame: 6 weeks
Locations:
city: Örebro
country: Sweden
facility: Örebro University
state: Örebro Län
Study officials:
affiliation: Örebro University, Sweden
name: Robert J Brummer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: