Bismuth Subsalicylate's Role in the Prevention of Travelers' Diarrhea

Study Overview
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Brief Summary
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The purpose of this study is to determine if the use of prophylactic bismuth subsalicylate (BSS) has an effect on the acquisition of travelers' diarrhea (TD) or antimicrobial resistance (AMR) genes in fecal samples among international travelers who departed from the United States to South East Asia, South Central Asia, or Africa. Our hypotheses will be tested using a double-blinded, placebo controlled randomized clinical trial with participants from a pre-travel health clinic in the United States.

Official Title
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Bismuth Subsalicylate's Role in the Prevention of Travelers' Diarrhea and Impact on Acquisition of Gut Antimicrobial Resistance Genes

Conditions
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Diarrhea Travelers, Antibiotic Resistant Infection

Intervention / Treatment
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* Drug: Bismuth subsalicylate
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be ≥ 18 and <70 years of age at the time of enrollment Sign an informed consent stating willingness to participate and comply with the study protocol Plan on leaving for an international trip ≥7 days after their pre-travel consultation Plan on traveling in country for ≥7 days but ≤21 days (21 day limit due to BSS duration recommendations and a lack of data on longer-term BSS use) Traveling to either South East Asia, South Central Asia, North Africa, or Sub-Saharan Africa for at least 7 days of their itinerary Be willing to complete an initial eligibility screening Be willing to complete questionnaires and provide biologic specimens (stool) within 7 days of departure and within 10 days after return Be willing to refrain from taking any pre-biotics, probiotic, synbiotic and/or herbal supplements throughout their study period Exclusion Criteria: Are <18 years of age or >69 years of age Are traveling in country for <7 or >21 days Have known or suspected contraindications to taking BSS (including, but not limited to, travelers with kidney disease, diabetes, gout, a clotting disorder, or an allergy to any component of BSS) Are pregnant (via self-report), are planning to become pregnant, or may become pregnant during travel (not actively using contraception and are sexually active), or are breastfeeding Routinely take a medication known to interact with BSS (including, but not limited to, insulin, methotrexate, valproic acid, angiotensin-converting enzyme inhibitors, anticoagulants, or other salicylates) Have taken an antibiotic in the 30 days before departure Have taken any medications that may lower one's ability to fight infection (e.g., steroids, monoclonal antibodies, etc.) Have previous diagnoses of immunocompromising conditions such as HIV/AIDS, complement deficiency, immunoglobulin deficiency, or undergoing active chemotherapy or participants with chronic gastrointestinal disorders, such as chronic diarrhea, irritable bowel syndrome (IBS), inflammatory bowel disease (i.e., Crohn's disease, ulcerative colitis), celiac disease, malabsorption syndromes, pancreatic insufficiency, gallbladder disease, or current gastrointestinal cancer Have had diarrhea anytime in the previous 30 days, have diarrhea at the pre-travel consultation, or develop diarrhea before departure Have been given doxycycline for malaria prophylaxis for the current trip (due to possible drug-drug interactions and decreased absorption of the doxycycline) Have an allergy to any component of the placebo tablets

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study will be conducted as a double-blinded, placebo-controlled randomized clinical trial.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention Group<br>Bismuth subsalicylate 4 tablets po bid (2.1 grams total of BSS) | Drug: Bismuth subsalicylate<br>* We aim to determine if there is a biologic benefit to an intervention (BSS administration) in the acquisition of travelers diarrhea and the acquisition of antimicrobial resistance genes.<br>* Other names: Pepto Bismol;|
| Placebo Comparator: Placebo<br>Placebo oral tablet 4 bid | Drug: Placebo Oral Tablet<br>* Placebo manufactured to mimic pepto bismol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Traveler's diarrhea | Self-reported TD | Change from baseline through 10 days post-travel | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut AMR genes | Pre- and post-travel stools will be tested for the presence/absence of AMR | Once within 7 days (before travel); once within 10 days (after travel) |