Validation of the Small Intestine Microbiome Aspiration (SIMBA) Capsule

Study Overview
=================
Brief Summary
-----------------
Prospective, open label trial to establish the ability of the SIMBA Capsule to accurately obtain a sample from the small bowel of participants with IBS (10 constipation-predominant (IBS-C) and 10 diarrhea-predominant (IBS-D)) and healthy participants (n=10). The accuracy of targeting the small bowel will be established by visual confirmation via X-ray. The clinical utility of the collected sample will be evaluated by analysis with samples obtained by the current gold standard (duodenal aspirate), as well as stool analysis and LBT.

Official Title
-----------------
Validation of the Small Intestine Microbiome Aspiration (SIMBA) Capsule

Conditions
-----------------
Proof of Concept, Irritable Bowel Syndrome

Intervention / Treatment
-----------------
* Device: Ingestible capsule
* Procedure: Sedated EGD
* Diagnostic Test: Lactulose Breath Test


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Aged between 18 and 70 years. Diagnosis of IBS by Rome 4 criteria (IBS groups) or no previous diagnosis of IBS or suspected IBS (Control group). Ability to understand and provide informed consent. Ability and willingness to meet the required schedule and study interventions. No planned change in diet or medical interventions during the study duration. Adequate mobility to transfer repeatedly between X-ray (standing or lying), and waiting (sitting). Willing and able to undergo a sedated esophagogastroduodenoscopy (EGD) with aspirate and brushing. Exclusion Criteria Prior gastrointestinal disease, surgery, or radiation treatment which, in the investigator's opinion, would lead to intestinal structuring or obstruction with a risk of capsule non-excretion (particular diseases which would be assessed on a case-by-case basis would include, achalasia, eosinophilic esophagitis, Crohn's disease, cancer diagnosis or treatment within the past year, or previous esophageal, gastric, small intestinal, or colonic surgery. Appendectomy or cholecystectomy more than 3 months prior to enrollment are acceptable). Use of any medications in the previous week that could substantially alter gastrointestinal motor function (e.g., opioids, prokinetics, anticholinergics, laxatives), or acidity (PPI, H2RA). History of oropharyngeal dysphagia or other swallowing disorder with a risk of aspiration of the capsule. Females of childbearing age who are not practicing birth control and/or are pregnant or lactating. No antibiotics, or colon cleanses/bowel prep for 2 weeks. < 2 bowel movements per week (Control Group).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IBS-D<br>Participant diagnosed with Irritable Bowel Syndrome, diarrhea predominant, confirmed by study doctors using Rome IV criteria. | Device: Ingestible capsule<br>* Participants will swallow capsules and collect in stool concurrent with stool samples<br>Procedure: Sedated EGD<br>* Participants will undergo sedated esophagogastroduodenoscopy (EGD) for collection of small intestine aspirate and simultaneous saliva sample.<br>Diagnostic Test: Lactulose Breath Test<br>* Hydrogen and methane breath test with lactulose substrate<br>|
| Active Comparator: IBS-C<br>Participant diagnosed with Irritable Bowel Syndrome, constipation predominant, confirmed by study doctors using Rome IV criteria. | Device: Ingestible capsule<br>* Participants will swallow capsules and collect in stool concurrent with stool samples<br>Procedure: Sedated EGD<br>* Participants will undergo sedated esophagogastroduodenoscopy (EGD) for collection of small intestine aspirate and simultaneous saliva sample.<br>Diagnostic Test: Lactulose Breath Test<br>* Hydrogen and methane breath test with lactulose substrate<br>|
| Active Comparator: Healthy Control<br>Participant with no ongoing medical conditions affecting GI health. | Device: Ingestible capsule<br>* Participants will swallow capsules and collect in stool concurrent with stool samples<br>Procedure: Sedated EGD<br>* Participants will undergo sedated esophagogastroduodenoscopy (EGD) for collection of small intestine aspirate and simultaneous saliva sample.<br>Diagnostic Test: Lactulose Breath Test<br>* Hydrogen and methane breath test with lactulose substrate<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bacterial composition | 1. Correlations of bacterial composition (superimposability of PLS-DA mapping) of samples collected by the SIMBA Capsule compared to small bowel aspirate and to mucosal microbiome sample obtained by brushing. (hypothesis: findings will be similar) | same day | 
| Bacterial composition | 2. Correlations of bacterial composition (superimposability of PLS-DA mapping) of samples collected by the SIMBA Capsule compared to stool sample obtained at same time. (hypothesis: findings will be different) | same day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bacterial composition | 1. Correlation of hydrogen- and methane-producing bacteria species (by 16s RNA sequencing) found by SIMBA Capsule with hydrogen and methane concentrations (peak and rise in ppm) detected by LBT and bacterial density (CFU/ml) of endoscopic aspirate. | within 5 days of primary measures |