Irritable Bowel Syndrome (IBS)
Conditions
Keywords
probiotic, irritable bowel syndome, ibs symptom severity, oro-anal transit time, randomized controlled trial
Brief summary
The goal of this double-blind parallel-arm randomized controlled trial is to learn if a probiotic supplement (containing a new strain derived from L. reuteri) alters outcomes related to symptom severity and transit time in adults with irritable bowel syndrome (IBS). The main question it aims to answer is: Does the probiotic alter IBS symptom severity? Researchers will compare the probiotic to a placebo (a lookalike substance that contains no probiotic) to see if the probiotic works to alter outcomes. Participants will: Be randomized to either take the probiotic supplement or placebo supplement daily for 12 weeks. Visit the lab for 4 study visits (visit 1: screening and informed consent; visit 2: randomization, data collection, beginning the intervention; visit 3: end of intervention and data collection; visit 4: 3 month post intervention follow up and data collection). Provide biological samples (blood, stool, saliva, urine) Complete questionnaires
Detailed description
The BIO-IBS study is a double-blind, randomized, placebo-controlled clinical trial investigating whether a combination probiotic improves symptoms in adults with irritable bowel syndrome (IBS). The trial also explores biological mechanisms and predictors of treatment response. Background & Rationale IBS is a common disorder of gut-brain interaction (\ 4% prevalence in Sweden). Current treatments include dietary, pharmacological, and psychological approaches. Increasing evidence suggests the gut microbiome plays a key role, prompting interest in probiotics. Aims 1\. Evaluate effect of probiotic combination on IBS symptoms. 2, Identify predictors of response. 3. Investigate IBS pathophysiology and biomarkers. Study Design Type: Double-blind, randomized, placebo-controlled, parallel-group Participants: 252 adults with IBS Randomization: 1:1 (probiotic vs placebo) Treatment duration: 12 weeks Follow-up: 3 months post-treatment Timeline: Recruitment starting April 2026 lasting \ 3 years Participants Inclusion Criteria Adult (≥18 years), IBS (Rome IV criteria) IBS-SSS \> 75 BMI 18.5-35 Able to consent and complete Swedish questionnaires Key Exclusion Criteria Significant gastrointestinal or systemic disease Recent antibiotics (within 3 months) or probiotics (within 2 weeks) Opioid use Pregnancy/breastfeeding Significant lab abnormalities (e.g., high fecal calprotectin) Major lifestyle/treatment changes Intervention Active treatment: Tablet containing both L. reuteri strains Placebo: Identical without bacteria Dose: 1 tablet twice daily Duration: 12 weeks Compliance ≥80% required for per-protocol analysis. Outcomes Primary Outcome Change in IBS symptom severity (IBS-SSS) from baseline to 12 weeks (intervention vs placebo) Secondary Outcomes Proportion achieving ≥50 or ≥100 point IBS-SSS reduction Gastrointestinal symptoms (GSRS-IBS) Pain reduction Quality of life (IBSQOL) Work productivity (WPAI:IBS) Transit time (gut motility) Adverse events Sustainability of effects (3-month follow-up) Exploratory Outcomes Stool consistency/frequency Biomarkers (microbiome, immune, metabolomics, etc.) Psychological and lifestyle factors Dietary influences Mechanistic insights into IBS Study Procedures Visits Screening (2-8 weeks before randomization Consent, questionnaires, biological samples, diaries Randomization (Day 0) Baseline assessments and start of treatment During intervention Regular symptom tracking Phone follow-up at week 6 End of treatment (12 weeks) Repeat assessments and samples Follow-up (3 months later) Long-term outcomes Optional (Facultative) Assessments Rectal sensitivity (barostat) Sigmoidoscopy ± confocal endomicroscopy MRI (motility and colonic volume) Measurements Questionnaires: IBS-SSS, GSRS-IBS, HADS, PHQ-15, IBSQOL, stress, work productivity Biological samples: blood, stool, urine, saliva Gut function: transit time (radiopaque markers and sweetcorn method) Diet: food frequency and recall diaries Statistical Considerations Sample size: 252 participants (powered to detect clinically meaningful IBS-SSS difference) Populations: Intention-to-treat (all randomized) Per-protocol (≥80% compliance, no major deviations) Analysis plan: Defined in a Statistical Analysis Plan No interim analysis Safety Probiotics considered safe with minimal risk (mainly transient flatulence). Adverse events will be recorded and classified by severity and causality. IBS symptom fluctuations are not counted as adverse events unless worsened. Ethics & Data Handling Conducted according to Declaration of Helsinki and ICH-GCP. Participants give informed consent and can withdraw anytime. Data are pseudonymized and securely stored (REDCap) Risk-Benefit Assessment Low risk due to established safety of L. reuteri strains Moderate participant burden (questionnaires, sample collection) Optional procedures may cause discomfort but are controlled and voluntary Potential benefit: improved IBS symptoms and better understanding of disease mechanisms Key Strengths Large sample size Rigorous randomized controlled design Comprehensive symptom, biological, and mechanistic assessment Long follow-up Conclusion This study aims to determine whether a novel probiotic combination improves IBS symptoms and to identify biological and clinical predictors of response, contributing to more personalized treatment strategies in IBS.
Interventions
OTHERProbiotic Supplementation (Lactobacillus Reuteri)
Probiotic using a new strain derived from L. reuteri.
OTHERPlacebo Supplementation
A placebo supplement that is identical to the probiotic in formulation and packaging except that the probiotic bacteria is not present.
Sponsors
Sahlgrenska University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with IBS according to ROME V criteria * IBS-SSS greater than or equal to 75 * Adult over 18 years old * BMI 18.5-35 kg/m2 * Able to understand the participant information sheet and willing to comply with the study protocol * Able to give informed consent * Able to complete the Swedish questionnaires
Exclusion criteria
* History of any gastroenterology disease including coeliac disease, heart, liver, neurological, or current psychiatric disease, diabetes, any surgery to the abdomen that affects intestinal function (not including cholecystectomy, appendectomy, ceasarean section). * The use of opioids 1 month prior to screening and throughout the study * The use of probiotic supplements from 14days before randomization and during the study (not including foods with probiotic components) * Consumption of antibiotics 3 months prior to screening and throughout the study * The start of any new drugs that affect the gastrointestinal tract or symptoms within the last month before the start of the study. As well as the start of new diets of psychological therapy as treatment for IBS symptoms. * Participation in any medical research during the last month * Clinically relevant lab abnormalities at the time of screening (fecal calprotectin greater than or equal to 150 ug/g as absolute cutoff. If calprotectin is between 50 - 150ug/g the decision is made on clinical judgement) * Pregnancy, plan to become pregnant during the study, breastfeeding * alcohol consumption \>14 units per week * Use of recreational active drugs during 1 month before screening or during the study * Use of medication that primarily affects bowel function, transit time, stool consistency 2 weeks before the intervention or during the 12 week intervention period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IBS symptom severity (IBS-Symptom-Severity-Score) | Screening (15-60 days pre-intervention), baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention | * Between group differences (intervention vs control) in mean IBS-SSS scores from baseline to end of intervention. * Proportion of responders (decrease in IBS-SSS over greater than or equal to 50 points from baseline to end of intervention) between arms * Proportion of greater responders (decrease in IBS-SSS scores greater than or equal to 100 points from baseline to end of intervention) between arms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gastrointestinal Symptom Rating Scale- IBS (GSRS-IBS) | Screening (15-60 days pre-intervention), baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention | Change in Gastrointestinal Symptom Rating Scale- IBS (GSRS-IBS) scores over time between arms The GSRS uses a 7- point Likert scale. Total scores can range from 15 - 105 with higher scores indicating worse symptom rating |
| General global assessment: satisfactory adequate relief of symptoms from baseline to end of intervention between arms | During intervention (days 14, 28, 42, 56, 70), end of intervention (day 84) | The proportion of individuals with greater or equal to 50% of assessments with an adequate relief of symptoms |
| General global assessment: worst pain over the last 24 hours, intervention group vs placebo group reduced between baseline and end of intervention between arms | During intervention (days 14, 28, 42, 56, 70), end of intervention (day 84) | The proportion of individuals with greater or equal to 50% of assessments between baseline and end of intervention, and a greater than or equal to 30% decrease in worst pain during the last 24 hours compared to baseline |
| IBS-quality of life (IBS-QoL) | Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention | Change in IBS-quality of life (IBS-QoL) scores over time between arms The IBS-QoL is a 34-item scale that uses a 5-point Likert scale with total scores ranging from 0-100, where higher scores indicate better quality of life |
| Work Productivity and Activity Impairment:IBS (WPAI:IBS) | Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention | Change in Work Productivity and Activity Impairment:IBS (WPAI:IBS) scores over time between arms The WPAI:IBS consists of 6 items regarding employment status, hours of work missed because of IBS, hours missed because of other reasons, hours actually worked, how much IBS affected productivity of working (VAS of 0 to 10), how much IBS affected regular activities (VAS of 0 to 10). Total scores are expressed as percentage of impairment/productivity lost with higher scores indicating greater impairment |
| Change in oro-anal transit time from baseline to end of intervention between groups: Radiopaque markers | Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84) | Participants will take oral tablets that are radiopaque markers following a specific protocol beginning from 7 days prior to attending the study visit. Each day they will swallow one set of radiopaque markers with water, then on day 7 a nurse will conduct an X-ray of the abdomen to show the location of the markers in the bowel. |
| Change in oro-anal transit time from baseline to end of intervention between groups: sweetcorn | Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84) | Sweetcorn oro-anal transit time will be measured using a specific protocol. 7 days before attending the study visit the participants will be advised to eat 100g of sweetcorn at 0800 with minimal chewing. Following this, each time they open their bowel for the next 6 days they will be advised to visually inspect the stool for sweetcorn and record whether or not they see the sweetcorn in a diary. |
| Hospital Anxiety and Depression Scale (HADS) | Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention | Change in Hospital Anxiety and Depression Scale (HADS) scores over time between groups. The HADS is a 14-item questionnaire (with 2 subscales: HADS-Depression (7 items) and HADS-Anxiety (7 items), with each item rated on a 4 point Likert scale. Total scores range from 0 - 21. Higher scores indicate worse symptoms for anxiety and depression |
| Patient Health Questionnaire (PHQ) | Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention | Change in Patient Health Questionnaire (PHQ) scores over time between groups The PHQ is a 15-item questionnaire with each item rated on a 3-point Likert scale. Total scores range from 0-30 with higher scores indicating greater somatic symptom burden |
Countries
Sweden
Contacts
CONTACTMagnus Simren, MD, PhD
CONTACTMagTarmlab office
PRINCIPAL_INVESTIGATORMagnus Simren, MD PHD
Göteborg University
Outcome results
None listed