ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 3 for:    Recruiting, Not yet recruiting, Available Studies | "Campylobacter Infections"
Previous Study | Return to List | Next Study

Epidemiology and Pathophysiology of Post-Infectious Functional GI Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03266068
Recruitment Status : Recruiting
First Posted : August 29, 2017
Last Update Posted : July 19, 2018
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Madhusudan (Madhu) Grover, MBBS, Mayo Clinic

Brief Summary:

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.


Condition or disease Intervention/treatment
Campylobacter Infections Irritable Bowel Syndrome Genetic: DNA Analysis of Blood Sample Procedure: Flexible sigmoidoscopy with colonic biopsies Procedure: Small bowel and colonic gastrointestinal permeability Diagnostic Test: Stool sample analysis

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 : Observational
Estimated Enrollment : 150 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Epidemiology and Pathophysiology of Post-Infectious Functional GI Disorders
Actual Study Start Date : September 2016
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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.




Primary Outcome Measures :
  1. 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.


Biospecimen Retention:   Samples With DNA
Blood, stool, and tissue samples


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Post Infectious IBS Cases Post Infectious with no IBS Controls Healthy Volunteer Controls
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03266068


Contacts
Contact: Wendy Sundt 507-293-4234 sundt.wendy@mayo.edu

Locations
United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Wendy J Sundt    507-293-4234    Sundt.Wendy@mayo.edu   
Sponsors and Collaborators
Mayo Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Madhusudan Grover, MBBS Mayo Clinic

Responsible Party: Madhusudan (Madhu) Grover, MBBS, Assistant Professor of Medicine, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03266068     History of Changes
Other Study ID Numbers: 12-006529
K23DK103911 ( U.S. NIH Grant/Contract )
P30DK084567 ( U.S. NIH Grant/Contract )
UL1TR000135 ( U.S. NIH Grant/Contract )
First Posted: August 29, 2017    Key Record Dates
Last Update Posted: July 19, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Irritable Bowel Syndrome
Campylobacter Infections
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gram-Negative Bacterial Infections
Bacterial Infections