Epidemiology and Pathophysiology of Post-Infectious Functional GI Disorders

January 19, 2022 updated by: Madhusudan (Madhu) Grover, MBBS, Mayo Clinic

Some people develop chronic abdominal pain with diarrhea or constipation after an episode of acute bacterial gastroenteritis. These symptoms can be consistent with post-infectious irritable bowel syndrome (IBS) and can last long after the acute infection is over. The exact reason why certain individuals develop these symptoms whereas others don't is not exactly clear.

The researchers are studying changes in gastrointestinal permeability (movement of contents across the lining of the intestine) and transit (movement of food through the gastrointestinal tract). The researchers are also studying if there are any genetic risk factors that are associated with development of this disorder.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The Centers for Disease Control and prevention (CDC) estimates that each year roughly 1 in 6 Americans (or 48 million people) contact food-borne illnesses. The CDC also estimates that between 20 and 40% of individuals traveling to a developing country get traveler's diarrhea. There is morbidity from these illnesses, even after the acute episode is over. Thus, up to a third of patients suffering from acute infectious gastroenteritis (IGE), most often resulting from a food-borne outbreak or travel develop chronic gastrointestinal (GI) illnesses such as irritable bowel syndrome (IBS). In addition, recent studies are suggesting that military personnel who suffered from IGE during deployment are more likely to suffer from IBS post-deployment. This disorder has been described as post-infectious IBS (PI-IBS).

Individuals with PI-IBS suffer from recurrent, debilitating abdominal pain and altered bowel function (diarrhea and/or constipation) and symptoms can be present for over 8 years after the acute IGE episode is over. It is estimated that up to 15% of the United States population suffers from IBS. This disorder creates significant impact on patient's daily functioning, overall quality of life and causes loss of work productivity. Despite the impact of this illness, treatment options for IBS have limited success, with a significant unmet need. Lack of understanding of underlying pathophysiological mechanisms has hampered development of effective treatment. More studies are required to enhance understanding of this disorder. Development of PI-IBS after an episode of acute IGE serves as a unique model to study risk-factors and mechanisms underlying PI-IBS and IBS in general. The researchers propose to study the epidemiological risk factors and pathophysiological mechanisms involved in the development of IBS among individuals suffering from episodes of acute IGE in the community.

Pathophysiology of IBS includes abnormalities of GI motility, sensation, mucosal defense, immune function and psychosocial factors. The researchers propose to investigate overall risk and patient demographic, pathogen and illness related characteristics as predictors for development of PI-IBS among patients who had suffered from acute IGE. In addition, the researchers want to determine pathophysiological mechanisms leading to the development of this disorder.

In order to achieve these goals, the researchers propose to establish collaboration with the Minnesota Department of Health (MDH) which conducts active surveillance for bacterial and parasitic cases of acute IGE and other reportable illnesses in Minnesota, as part of the mandate to detecting outbreaks and prioritize control efforts. We plan to establish retrospective and prospective cohorts in this proposal. A randomly selected sub-set of these patients will be invited to Mayo Clinic for detailed investigations including assessment of GI motility, permeability, endoscopic examination for colon biopsies, and diverse blood and stool assays using techniques that are all validated to provide information about the mechanism of PI-IBS. The researchers will also investigate variations in the barrier function pathway genes in tissues of PI-IBS patients and to understand the contribution of these genetic variations in immune activation and control of barrier function to increased susceptibility to PI-IBS.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Post Infectious IBS Cases Post Infectious with no IBS Controls Healthy Volunteer Controls

Description

Post Infectious IBS Cases Inclusion Criteria:

  1. IBS by Rome III criteria
  2. No abdominal surgery (except hernia, C-section, hysterectomy, appendectomy and cholecystectomy)

Post Infectious with no IBS Controls Inclusion Criteria:

  1. No IBS by Rome III criteria
  2. No abdominal surgery (except hernia, C-section, hysterectomy, appendectomy and cholecystectomy)

Post Infectious IBS Cases and Post Infectious with no IBS Controls Exclusion Criteria:

  1. Prior history of IBS or inflammatory bowel disease (IBD) (Crohn's disease or ulcerative colitis), microscopic colitis or celiac disease
  2. Ingestion of artificial sweeteners such as sucralose, aspartame, lactulose or mannitol 2 days before the study begins, e.g., foods to be avoided are sugarless gums or mints and diet soda

  3. Ingestion of any prescription, over the counter, or herbal medications which can affect gastrointestinal transit 7 days before study begins

    1. Any treatment specifically taken for IBS, including loperamide, cholestyramine, alosetron
    2. Drugs with a known pharmacological activity at serotonin type 4 (5-HT4), serotonin receptor 2B (5-HT2b) or 5-HT3 receptors (e.g, tegaserod, ondansetron, tropisetron, granisetron, dolasetron, mirtazapine)
    3. All narcotics (e.g, codeine, morphine, and propoxyphene, either alone or in combination)
    4. Anti-cholinergic agents (e.g, dicyclomine, hyoscyamine, propantheline)
    5. Ultram

    6. GI preparations

      • Anti-nausea agents (e.g, trimethobenzamide, promethazine, prochlorperazine, dimenhydrinate, hydroxyzine)
      • Osmotic laxative agents (e.g, lactulose, sorbitol or polyethylene glycol (PEG) solutions as Miralax and Glycolax)
      • Prokinetic agents (e.g, cisapride, metoclopramide, itopride, domperidone)
    7. Antimuscarinics
    8. Peppermint oil
    9. Systemic antibiotics, rifaximin, metronidazole
  4. Any females who are pregnant or trying to become pregnant (due to radiation exposure)
  5. Bleeding disorders or medications that increase risk of bleeding from mucosal biopsies

Healthy Control Inclusion Criteria:

  1. No abdominal surgery (except hernia, C-section, hysterectomy, appendectomy and cholecystectomy)
  2. No history of acute gastroenteritis, food-poisoning or travel related diarrhea within last 2 years.

Healthy Control Exclusion Criteria:

  1. Prior history of IBS or IBD (Crohn's disease or ulcerative colitis), microscopic colitis or celiac disease
  2. Ingestion of artificial sweeteners such as sucralose, aspartame, lactulose or mannitol 2 days before the study begins, e.g., foods to be avoided are sugarless gums or mints and diet soda

  3. Ingestion of any prescription, over the counter, or herbal medications which can affect gastrointestinal transit 7 days before study begins

    1. Any treatment specifically taken for IBS, including loperamide, cholestyramine, alosetron
    2. Drugs with a known pharmacological activity at 5-HT4, 5-HT2b or 5-HT3 receptors (e.g, tegaserod, ondansetron, tropisetron, granisetron, dolasetron, mirtazapine)
    3. All narcotics (e.g, codeine, morphine, and propoxyphene, either alone or in combination)
    4. Anti-cholinergic agents (e.g, dicyclomine, hyoscyamine, propantheline)
    5. Ultram

    6. GI preparations

      • Anti-nausea agents (e.g, trimethobenzamide, promethazine, prochlorperazine, dimenhydrinate, hydroxyzine)
      • Osmotic laxative agents (e.g, lactulose, sorbitol or PEG solutions as Miralax and Glycolax)
      • Prokinetic agents (e.g, cisapride, metoclopramide, itopride, domperidone)
    7. Antimuscarinics
    8. Peppermint oil
    9. Systemic antibiotics, rifaximin, metronidazole
  4. Any females who are pregnant or trying to become pregnant (due to radiation exposure)
  5. Bleeding disorders or medications that increase risk of bleeding from mucosal biopsies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Post Infectious IBS Case
Subjects who have suffered from acute bacterial gastroenteritis within last two years and have developed some symptoms that might be suggestive of post-infectious irritable bowel syndrome (IBS). Subjects will receive a DNA analysis of blood sample, flexible sigmoidoscopy with colonic biopsies, small bowel and colonic gastrointestinal permeability, and stool sample analysis.
Genetic: DNA Analysis of Blood Sample
DNA analysis of the genes possibly involved in IBS.
Procedure: Flexible sigmoidoscopy with colonic biopsies
Endoscopy of the subject's lower colon in which biopsies of the lining of the colon will be taken.
Procedure: Small bowel and colonic gastrointestinal permeability
A validated scintigraphic method to measure gastric, small bowel and colonic transit will be used.
Diagnostic test: Stool sample analysis
Stool samples will be used to extract supernatants. These supernatants will be studied in using chamber set-up to determine barrier effects on T84 monolayers.
Post Infectious with no IBS Control
Subjects who have suffered from acute bacterial gastroenteritis within last two years and have not developed symptoms suggestive of post-infectious irritable bowel syndrome (IBS). Subjects will receive a DNA analysis of blood sample, flexible sigmoidoscopy with colonic biopsies, small bowel and colonic gastrointestinal permeability, and stool sample analysis.
Genetic: DNA Analysis of Blood Sample
DNA analysis of the genes possibly involved in IBS.
Procedure: Flexible sigmoidoscopy with colonic biopsies
Endoscopy of the subject's lower colon in which biopsies of the lining of the colon will be taken.
Procedure: Small bowel and colonic gastrointestinal permeability
A validated scintigraphic method to measure gastric, small bowel and colonic transit will be used.
Diagnostic test: Stool sample analysis
Stool samples will be used to extract supernatants. These supernatants will be studied in using chamber set-up to determine barrier effects on T84 monolayers.
Healthy Control
Healthy volunteers; subjects will receive a DNA analysis of blood sample, flexible sigmoidoscopy with colonic biopsies, small bowel and colonic gastrointestinal permeability, and stool sample analysis.
Genetic: DNA Analysis of Blood Sample
DNA analysis of the genes possibly involved in IBS.
Procedure: Flexible sigmoidoscopy with colonic biopsies
Endoscopy of the subject's lower colon in which biopsies of the lining of the colon will be taken.
Procedure: Small bowel and colonic gastrointestinal permeability
A validated scintigraphic method to measure gastric, small bowel and colonic transit will be used.
Diagnostic test: Stool sample analysis
Stool samples will be used to extract supernatants. These supernatants will be studied in using chamber set-up to determine barrier effects on T84 monolayers.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Colonic geometric center at 24 hours
Time Frame: 24 hours
The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mayo Clinic

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2016

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 11, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 11, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 5, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 28, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 29, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 20, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 19, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 12-006529
  • UL1TR000135 (U.S. NIH Grant/Contract)
  • K23DK103911 (NIH)
  • P30DK084567 (NIH)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Irritable Bowel Syndrome

Clinical Trials on DNA Analysis of Blood Sample

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings