A Pilot Study Assessing Intestinal Microbiota Diversification and Changes After Travel to South(East) Asia From the US

Dysbiosis Clinical Trial

— ABROAD  

Official title:

A Pilot Study to Assess the Intestinal MicroBiota Diversification States and Changes in U.S. Travelers After Return From Short-Term Travel to an Overseas South(East) Asian Destination

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03043300
• Other study ID #: IRB00092426
• Secondary ID: 16IPA1609428
• Status: Completed
• Start date: November 7, 2017
• Est. completion date: December 1, 2018

Study information

• Verified date: January 2019
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This prospective, observational pilot study is designed to assess feasibility, refine the target population, and quickly test qualitative and quantitative changes in the microbiome after short-term travel to South or Southeast Asia, regions where rates of travelers' diarrhea and intestinal colonization with antimicrobial resistant bacteria are highest.

To measure the diversity change of the intestinal microbiota, participants will complete a questionnaire and provide a stool specimen at three different time points: prior to traveling, two weeks after returning from traveling, and 14 weeks after returning from traveling.

Description:

Travelers' diarrhea is the most common illness experienced by those going overseas. Estimates vary, but incidence has been reported to range between 30-60%, depending on travel destination and season. Multiple organisms have been implicated as causes of travelers' diarrhea, but bacteria account for 80-90% of cases. There is mounting evidence that the integrity of the intestinal microbiome may be a strong modulator of diarrheal disease, and that intestinal infections and other factors, including stress, antibiotic exposure, and diet may disrupt the diversity and overall composition of the microbiome. Dysbiosis, a state of altered microbiota diversity, may be less resistant to the acquisition of intestinal pathogens and colonization of multiple drug resistant organisms. Furthermore, disruptions in the microbiome that may result from an episode of travelers' diarrhea may have a role in the development of chronic diarrhea and post-infectious irritable bowel syndrome.

This prospective, observational pilot study is intended to obtain preliminary data to support the rationale for a subsequent larger cohort study. This study is designed to assess feasibility, refine the target population, and quickly test qualitative and quantitative changes in the microbiome after short-term travel (seven to 21 days) to South or Southeast Asia, regions where rates of travelers' diarrhea and intestinal colonization with antimicrobial resistant bacteria are highest.

The target population will include 10 Emory University students and/or Emory University Hospital TravelWell Clinic (TWC) patients who have international travel plans. Consented, willing, and eligible participants will complete an initial eligibility screening, followed by pre-travel, short-term post-travel, and long-term post-travel study visits. To determine specific factors associated with diversity change of the intestinal microbiota and changes in the presence of genes that code for antibiotic resistance, questionnaires designed to collect data on demographics, medical history, diet, food intake, recent (within 12 weeks of pre-travel assessment, during travel, or post-travel) illness history, medication use, travel itinerary, travel activities, and relevant food and water risk behaviors will be completed at each study visit. A stool sample will also be provided at each time point. Participants may also choose to take part in an optional sub-study which involves banking leftover stool for future research use.

The primary protocol objective is to pilot a study investigating the association between travel and changes in the intestinal microbiome (including both bacterial and fungal components) and the bacterial and fungal resistome.

The secondary protocol objective is to assess microbiota profile changes and reversion to or toward the pre-travel state by comparing pre-travel stool specimen sequencing results to short-term post-travel and long-term post-travel stool specimen sequencing results.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 1, 2018
• Est. primary completion date: December 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Ability to understand and the willingness to sign a written informed consent document.

2. Ability and willingness to comply with study protocol requirements.

3. Completed screening criteria.

4. Departure date for international travel is planned for 4 weeks from the date of informed consent.

5. Duration of international travel is planned for a minimum of seven days and maximum of 21 days.

6. International travel is planned to at least one of the following countries of South(east) Asia:

1. South Asia, defined as: Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, Sri Lanka

2. Southeast Asia, defined as: Cambodia, Laos, West Malaysia (excluding Malaysian Borneo), Myanmar (Burma), Thailand, Vietnam

Exclusion Criteria:

1. Women of childbearing potential who self-report to be either:

1. Currently pregnant

2. Planning a pregnancy during study participation

2. Current diarrhea (defined as = 3 unformed loose stools in 24 hours)

3. Prior episode of diarrhea (defined as = 3 unformed loose stools in 24 hours) in the 12 weeks prior to date of informed consent

Related Conditions & MeSH terms

• Dysbiosis

Intervention

Other:
• Screening Criteria Review
The screening criteria review is an 8 item instrument collecting information during screening about overall health, including self-reported chronic intestinal conditions, immunocompromising conditions, the use of certain medication types (immunosuppressives and antibiotics), and pregnancy status. The instrument will also collect dates of planned travel to South(east) as well as preferred dates for study visits and reminder contacts. This instrument will be administered verbally by the study team and completed no more than 4 weeks prior to travel departure from the United States.
• Pre-Travel Questionnaire
The pre-travel questionnaire is a 29 item instrument collecting information about baseline characteristics, dietary habits, travel plans, and health history. This questionnaire will be administered verbally by the study team and completed 1 week prior to travel departure from the United States.
• Pre-Travel Stool Specimen Collection
The pre-travel stool specimen collection will occur 1 week prior to travel departure from the United States. The processing and analyses of this stool specimen will be performed by the Centers for Disease Control and Prevention.
• Short-Term Post-Travel Questionnaire
The short-term post-travel questionnaire is a 19 item instrument collecting information about dates and locations of travel, food and beverages consumed while traveling, and illnesses during or following traveling. This questionnaire will be administered verbally by the study team and completed 2 weeks after returning to the United States from travel.
• Short-Term Post-Travel Stool Specimen Collection
The short-term post-travel stool specimen collection will occur 2 weeks after returning to the United States from travel. The processing and analyses of this stool specimen will be performed by the Centers for Disease Control and Prevention.
• Long-Term Post-Travel Questionnaire
The long-term post-travel questionnaire is a 16 item instrument collecting information about illnesses since last study visit, dietary habits since last study visit, and any traveling since the last visit. This questionnaire will be administered verbally by the study team and completed 14 weeks after returning to the United States from travel.
• Long-Term Post-Travel Stool Specimen Collection
The short-term post-travel stool specimen collection will occur 14 weeks after returning to the United States from travel. The processing and analyses of this stool specimen will be performed by the Centers for Disease Control and Prevention.

Locations

Country	Name	City	State
United States	Emory Univeristy Hospital Midtown, TravelWell Center	Atlanta	Georgia
United States	Emory University	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	Centers for Disease Control and Prevention

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Predominant Intestinal Microbiota Genus or Strain	A genus of strain will be considered predominant if it represents at least 30% of all genus or strains of microbiota within the stool sample.	Pre-travel to 14 Weeks Post-Travel
Primary	Change in Alpha and Beta Diversity of Intestinal Microbiota	Maximum percentage of all genes identified included within the same taxon will be determined from each stool sample.	Pre-travel to 14 Weeks Post-Travel
Primary	Change in Firmicutes:Bacteroides Ratio of Microbiota	Firmicutes and Bacteroides are groups of bacteria present in the gut and the Firmicutes to Bacteroidetes ratio is considered a significant aspect of microbiota composition. The Firmicutes to Bacteroidetes ratio will be determined from each stool sample.	Pre-travel to 14 Weeks Post-Travel
Primary	Change in Enteropathogens of Stool Microbiota	The presence of enteropathogens in stool samples will be examined pre- and post-travel.	Pre-travel to 14 Weeks Post-Travel
Primary	Change in Stool Resistome	Review of the resistome will include a summary of the overall number and diversity of bacterial and fungal resistance genes including any new acquisition.	Pre-travel to 14 Weeks Post-Travel
Secondary	Reversion toward pre-travel microbiota state	Microbiota profile changes and reversion to or toward the pre-travel state will be assessed by comparing pre-travel stool specimen sequencing results to short-term post-travel and long-term post-travel stool specimen sequencing results.	Pre-travel to 14 Weeks Post-Travel