Irritable Bowel Syndrome (IBS), Microbiome
Conditions
Brief summary
This study is intended to characterize longitudinal changes in the small intestinal microbiome following rifaximin treatment in participants with Irritable Bowel Syndrome (IBS) over a 12 week period.
Detailed description
The goal of this open-label interventional trial is to evaluate the changes in the small intestinal microbiome in a population of 180 adults with irritable bowel syndrome (IBS) over a twelve week period. The study will compare microbiome data collected with the SIMBA capsule before, during and after treatment, along with qualitative questionnaires.
Interventions
DRUGRifaximin (drug)
Open label
DEVICEfluid biopsy capsule
Collection of a fluid biopsy from the small intestine via ingestible capsule
Sponsors
University of Calgary
Nimble Science Ltd.
Genome Alberta
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-65 years at the inclusion of the study, both female and male subjects. 2. Provide informed consent to participate in study; willing and able to comply with study procedures. 3. Able to swallow a capsule sized 25mm length and 9mm width (i.e. large dose omega 3 pill). 4. Willing to maintain their diet and physical activity levels during the study. 5. Participants with a confirmed or suspected diagnosis of Irritable Bowel Syndrome (IBS) meeting or presenting with symptoms consistent with Rome V criteria for one of the following subtypes: IBS-C, IBS-M, or IBS-D. 6. Baseline weekly average of worst daily (in past 24 hours) abdominal bloating score of \>= 3.0 on a 0-to-10-point scale.
Exclusion criteria
1. Non-English speaking. 2. Regular use of probiotics, prebiotics or synbiotics (including food and drinks containing added probiotics and/or probiotic yogurts with live, active cultures, or kefir) within 1 month prior to screening. Non-probiotic fortified yogurt is acceptable. Potential participants may be eligible once a 1-month washout is completed. 3. Stimulant laxative use (includes bisacodyl/Dulcolax, senna/Senekot, cascara, or fiber supplements) is allowed if it is kept unchanged in the week prior to the SIMBA capsule ingestion. Osmotic laxatives (polyethylene glycol (PEG; other trade names), milk of magnesia, lactulose), stool softeners (docusate; other trade names) or secretagogues (linaclotide/Constella, plecanatide/Trulance, tenapanor/Ibsrela should not be used within 7 days of taking the SIMBA capsules. 4. Use of oral or intravenous antibiotics or antifungal medications (except topical antibiotics or antifungals) within the previous 12 weeks. This includes rifaximin. 5. Use of medications known to affect gastrointestinal motility, including but not limited to prokinetics (including domperidone, metoclopramide, prucalopride), anticholinergics, opioids, GLP-1 receptor agonists, secretagogues (linaclotide, plecanatide, tenapenor), cholestyramine, colchicine, and methyldopa, unless permitted by protocol. 6. Chronic use of salicylates, aspirin (ASA), corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), misoprostol or other medications known to affect small intestinal mucosal integrity, as determined by the Principal Investigator. 7. Current smoker or use of tobacco, nicotine, or cannabis products including vapes, gums, gummies, or other ingestible or inhaled formats. 8. Alcohol consumption \>21 units per week, alcohol abuse, or illicit drug use. 9. Currently dieting for weight loss or following a low-carbohydrate diet. 10. Participation in another clinical trial within 30 days prior to enrollment. 11. Known allergy or hypersensitivity to rifaximin. 12. Pregnancy, lactation, planned pregnancy during the study period, or unwillingness to use an approved method of contraception if of childbearing potential. 13. Major surgery within the previous 3 months. 14. Any significant medical condition that, in the opinion of the Principal Investigator or Qualified Investigator, could interfere with study participation, intervention, or outcome assessment, including: * Renal disease * Gastrointestinal disorders (includes inflammatory bowel disease, celiac disease (treated or untreated), any eosinophilic gastrointestinal disorder, microscopic colitis) * Autoimmune disease (including Rheumatoid arthritis, lupus, scleroderma) * Metabolic disease (type 1 diabetes is excluded. Controlled Type 2 diabetes may be acceptable per investigator's discretion) * Cardiovascular or vascular disease * Respiratory disease (COPD, home oxygen use is excluded. Mild asthma (prn puffer use) may be acceptable) * major mental health disorder * Hyperthyroidism (whether controlled or not). Controlled hypothyroidism is allowable 15. Prior fecal microbiota transplantation, less than a year before study enrollment. 16. Cancer diagnosis or treatment within the past year (except non-melanoma skin cancer). Concomitant Supplements Participants taking supplements that are judged by the investigators not to interfere with study outcomes (e.g., vitamins, omega-3 fatty acids, creatine monohydrate) may continue use, provided the dose remains unchanged throughout the study, are not taken within 6 hours on either side of capsule ingestion, and no new supplements are introduced unless medically recommended. Pregnancy Assessment Females of childbearing potential will be assessed for pregnancy risk through self-report. A urine β-hCG test will be required if pregnancy status is uncertain. Participants who become pregnant during the study will discontinue the study medication immediately and notify the investigators.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in small intestinal microbiome composition | Baseline and 4 weeks post end of treatment | Difference in small intestinal microbiome composition (Community Distance Index) within participant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Abdominal Pain Severity (VAS-IBS) | Baseline and 4 weeks post end of treatment | Change in participant's abdominal pain sub-score measured using the Visual Analogue Scale for Irritable Bowel Syndrome (VAS-IBS) |
| Difference in Dominant Microbial Composition Index Among IBS Rome V Subtypes | Baseline and 4 weeks post end of treatment | Dominant microbial composition index will be developed using shotgun metagenomic sequencing and metabolome analysis of capsule samples for each IBS sub-type (D, C and M) by collating sample results for participants by study arm. This microbial composition index for each arm will be described and differences compared. |
| Change in Antimicrobial Resistance Gene Burden and Microbial Antimicrobial Resistance | Baseline and 4 weeks post end of treatment | Characterize intrinsic antimicrobial resistance (AMR) profiles of microbial species and subspecies identified in small intestinal samples via shotgun sequencing, measured through copy numbers of NCBI AMRFinder+ genome annotations. |
| Predictive Accuracy of Baseline Multi-Omic Features for Clinical Response to Rifaximin | Baseline and 4 weeks post end of treatment | Microbiome feature selection and documentation (p-Values, effect size) based on Linear Mixed Effect modelling of clinical response. Model performance metrics (e.g., discrimination, calibration, and predictive accuracy) for predicting clinical response to rifaximin using baseline clinical characteristics and small intestinal multi-omic features measured via shotgun sequencing and metabolomic analysis. |
Countries
Canada
Contacts
CONTACTLynn Wilsack, MSc
PRINCIPAL_INVESTIGATORChristopher N Andrews, MD MSc
University of Calgary
Outcome results
None listed