Bismuth Subsalicylate's Role in the Prevention of Travelers' Diarrhea and Impact on Acquisition of Gut Antimicrobial Resistance Genes
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 482
- 试验地点
- 1
- 主要终点
- Traveler's Diarrhea
研究概览
简要总结
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.
详细描述
This study is a double-blind, placebo-controlled randomized clinical trial designed to evaluate the effectiveness of bismuth subsalicylate (BSS) in preventing travelers' diarrhea (TD) and its potential impact on the acquisition of antimicrobial resistance (AMR) genes and changes in the gut microbiome among international travelers.
Adult participants (18-69 years) planning travel from the United States to high-risk regions, including South East Asia, South Central Asia, and Africa, will be recruited from a pre-travel health clinic. Eligible participants will be randomized to receive either BSS (4 tablets twice daily; total daily dose approximately 2.1 g) or a matching placebo. Study medication will begin prior to arrival at the destination and continue throughout the duration of travel (up to 21 days).
Participants will complete standardized questionnaires before travel, daily during travel, and after returning to the United States. These questionnaires will capture information on medication adherence, gastrointestinal symptoms, development of TD, healthcare utilization, and adverse events. TD will be defined as three or more unformed stools within a 24-hour period, with or without associated symptoms.
To evaluate secondary objectives, participants will provide stool samples within 7 days prior to departure and within 10 days after return. These samples will be analyzed to assess acquisition of AMR genes using molecular methods and to evaluate changes in the gut microbiome, including the presence of enteric pathogens.
The primary objective is to determine whether prophylactic BSS reduces the incidence of TD among international travelers. Secondary objectives include assessing the impact of BSS on acquisition of AMR genes and evaluating changes in the gut microbiome associated with travel and intervention use.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Intervention Group
Bismuth subsalicylate 4 tablets po bid (2.1 grams total of BSS)
干预措施: Bismuth subsalicylate (Drug)
结局指标
主要结局
Traveler's Diarrhea
时间窗: Change from baseline through 10 days post-travel
Incidence of travelers' diarrhea, defined as self-reported occurrence of three or more unformed stools within a 24-hour period with or without associated gastrointestinal symptoms during travel or within 10 days after return.
次要结局
- Gut AMR Genes(Once within 7 days (before travel); once within 10 days (after travel))
研究者
Kristina Angelo
Medical Epidemiologist; Study co-Principal Investigator
Centers for Disease Control and Prevention