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

IBS Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03986476
• Other study ID #: 2018/450
• Status: Completed
• Phase: N/A
• Start date: March 26, 2019
• Est. completion date: May 10, 2021

Study information

• Verified date: September 2021
• Source: Örebro University, Sweden
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: May 10, 2021
• Est. primary completion date: May 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• IBS
• Irritable Bowel Syndrome

Intervention

Dietary Supplement:
• Probiotics
5x10^8 colony forming units (CFU) of each probiotic strain, two capsules per day over six weeks

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

Locations

Country	Name	City	State
Sweden	Örebro University	Örebro	Örebro Län

Sponsors (1)

Lead Sponsor	Collaborator
Örebro University, Sweden

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in stool frequency and consistency (daily diary on bowel movement using Bristol Stool Chart)	Difference between intervention with the probiotic products compared to the placebo in stool frequency and consistency	3 weeks
Other	Change in stool frequency and consistency (daily diary on bowel movement using Bristol Stool Chart)	Difference between intervention with the probiotic products compared to the placebo in stool frequency and consistency	6 weeks
Other	Change in gastrointestinal symptoms measured by the IBS-specific gastrointestinal symptom rating scale (GSRS-IBS)	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)	3 weeks
Other	Change in gastrointestinal symptoms measured by the IBS symptom severity score (IBS-SSS)	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)	3 weeks
Other	Change in gastrointestinal symptoms measured by the IBS-specific gastrointestinal symptom rating scale (GSRS-IBS)	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 weeks
Other	Change in gastrointestinal symptoms measured by the IBS symptom severity score (IBS-SSS)	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)	6 weeks
Other	Change in quality of life measured by IBS-specific quality of life (IBS-QOL) questionnaire	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)	3 weeks
Other	Change in quality of life measured by IBS-specific quality of life (IBS-QOL) questionnaire	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)	6 weeks
Other	Change in perceived stress using the perceived stress scale (PSS)	Difference between intervention with the probiotic products compared to the placebo in perceived stress (PSS range 0-40: 0-no stress, 40-high stress)	3 weeks
Other	Change in perceived stress using the perceived stress scale (PSS)	Difference between intervention with the probiotic products compared to the placebo in perceived stress (PSS range 0-40: 0-no stress, 40-high stress)	6 weeks
Other	Change in anxiety and depression symptoms using the Hospital Anxiety and Depression Scale (HADS)	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)	3 weeks
Other	Change in anxiety and depression symptoms using the Hospital Anxiety and Depression Scale (HADS)	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)	6 weeks
Other	Change in salivary cortisol levels	Difference between intervention with the probiotic products compared to the placebo in salivary cortisol levels	3 weeks
Other	Change in salivary cortisol levels	Difference between intervention with the probiotic products compared to the placebo in salivary cortisol levels	6 weeks
Other	Change in intestinal microbiota composition (16S rRNA-based next generation sequencing of faecal samples) after probiotic intervention	Difference between intervention with the probiotic products compared to the placebo in intestinal microbiota composition	3 weeks
Other	Change in intestinal microbiota composition (16S rRNA-based next generation sequencing of faecal samples) after probiotic intervention	Difference between intervention with the probiotic products compared to the placebo in intestinal microbiota composition	6 weeks
Other	Change in metabolomic profile in faecal samples after probiotic intervention	Difference between intervention with the probiotic products compared to the placebo in metabolomic profile in faecal samples	3 weeks
Other	Change in metabolomic profile in faecal samples after probiotic intervention	Difference between intervention with the probiotic products compared to the placebo in metabolomic profile in faecal samples	6 weeks
Other	Change in metabolomic profile in blood samples after probiotic intervention	Difference between intervention with the probiotic products compared to the placebo in metabolomic profile in faecal samples	3 weeks
Other	Change in metabolomic profile in blood samples after probiotic intervention	Difference between intervention with the probiotic products compared to the placebo in metabolomic profile in faecal samples	6 weeks
Primary	Change in small intestinal permeability after 6 weeks (urinary lactulose/rhamnose ratio, 0-5h)	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	6 weeks
Secondary	Change in small intestinal permeability after 3 weeks (urinary lactulose/rhamnose ratio, 0-5h)	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	3 weeks
Secondary	Change in whole gut permeability after 6 weeks (urinary sucralose/erythritol ratio, 0-24h)	Difference between intervention with the probiotic products compared to the placebo in whole gut permeability, measured as urinary sucralose/erythritol excretion ratio (0-24hrs)	6 weeks
Secondary	Change in whole gut permeability after 3 weeks (urinary sucralose/erythritol excretion ratio, 0-24h)	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 weeks
Secondary	Change in colonic permeability after 6 weeks (urinary sucralose/erythritol ratio, 5-24h)	Difference between intervention with the probiotic products compared to the placebo in colonic permeability, measured as urinary sucralose/erythritol ratio (5-24hrs)	6 weeks
Secondary	Change in colonic permeability after 3 weeks (urinary sucralose/erythritol ratio, 5-24hrs)	Difference between intervention with the probiotic products compared to the placebo in colonic permeability, measured as urinary sucralose/erythritol ratio (5-24hrs)	3 weeks
Secondary	Change in gastroduodenal permeability after 6 weeks (urinary sucrose excretion, 0-5hrs)	Difference between intervention with the probiotic products compared to the placebo in gastroduodenal permeability, measured as urinary sucrose excretion (0-5hrs)	6 weeks
Secondary	Change in gastroduodenal permeability after 3 weeks (urinary sucrose excretion, 0-5hrs)	Difference between intervention with the probiotic products compared to the placebo in gastroduodenal permeability, measured as urinary sucrose excretion (0-5hrs)	3 weeks
Secondary	Change in inflammatory status after 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)	3 weeks
Secondary	Change in inflammatory status after 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)	6 weeks