Diarrhea Travelers, Antibiotic Resistant Infection
Conditions
Brief summary
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.
Interventions
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.
DRUGPlacebo Oral Tablet
Placebo manufactured to mimic pepto bismol
Sponsors
Centers for Disease Control and Prevention
Procter and Gamble
The New York Center for Travel and Tropical Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This study will be conducted as a double-blinded, placebo-controlled randomized clinical trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
Yes
Inclusion criteria
1. Be ≥ 18 and \<70 years of age at the time of enrollment 2. Sign an informed consent stating willingness to participate and comply with the study protocol 3. Plan on leaving for an international trip ≥7 days after their pre-travel consultation 4. 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) 5. Traveling to either South East Asia, South Central Asia, North Africa, or Sub-Saharan Africa for at least 7 days of their itinerary 6. Be willing to complete an initial eligibility screening 7. Be willing to complete questionnaires and provide biologic specimens (stool) within 7 days of departure and within 10 days after return 8. Be willing to refrain from taking any pre-biotics, probiotic, synbiotic and/or herbal supplements throughout their study period
Exclusion criteria
1. Are \<18 years of age or \>69 years of age 2. Are traveling in country for \<7 or \>21 days 3. 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) 4. 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 5. 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) 6. Have taken an antibiotic in the 30 days before departure 7. Have taken any medications that may lower one's ability to fight infection (e.g., steroids, monoclonal antibodies, etc.) 8. 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 9. Have had diarrhea anytime in the previous 30 days, have diarrhea at the pre-travel consultation, or develop diarrhea before departure 10. Have been given doxycycline for malaria prophylaxis for the current trip (due to possible drug-drug interactions and decreased absorption of the doxycycline) 11. Have an allergy to any component of the placebo tablets
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Traveler's Diarrhea | Change from baseline through 10 days post-travel | Self-reported TD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gut AMR Genes | Once within 7 days (before travel); once within 10 days (after travel) | Pre- and post-travel stools will be tested for the presence/absence of AMR genes |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBradley Connor, MD
The New York Center for Travel and Tropical Medicine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention Group Bismuth subsalicylate 4 tablets po bid (2.1 grams total of BSS)
Bismuth subsalicylate: 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. | 136 |
| Placebo Placebo oral tablet 4 bid
Placebo Oral Tablet: Placebo manufactured to mimic pepto bismol | 134 |
| Total | 270 |
Baseline characteristics
| Characteristic | Intervention Group | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 32 years | 32 years | 32 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 16 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 116 Participants | 239 Participants | 123 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 15 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 23 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 56 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 25 Participants | 46 Participants | 21 Participants |
| Race (NIH/OMB) White | 73 Participants | 144 Participants | 71 Participants |
| Region of Enrollment United States | 136 participants | 270 participants | 134 participants |
| Sex/Gender, Customized Female | 84 Participants | 169 Participants | 85 Participants |
| Sex/Gender, Customized Male | 51 Participants | 100 Participants | 49 Participants |
| Sex/Gender, Customized Missing | 1 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 136 | 0 / 134 |
| other Total, other adverse events | 0 / 136 | 0 / 134 |
| serious Total, serious adverse events | 0 / 136 | 0 / 134 |
Outcome results
Primary
Traveler's Diarrhea
Self-reported TD
Time frame: Change from baseline through 10 days post-travel
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Group | Traveler's Diarrhea | 27 Participants |
| Placebo | Traveler's Diarrhea | 26 Participants |
Secondary
Gut AMR Genes
Pre- and post-travel stools will be tested for the presence/absence of AMR genes
Time frame: Once within 7 days (before travel); once within 10 days (after travel)