Serine Proteases in Gastrointestinal Function and Irritable Bowel Syndrome (IBS)



Status:Completed
Conditions:Irritable Bowel Syndrome (IBS), Gastrointestinal
Therapuetic Areas:Gastroenterology
Healthy:No
Age Range:18 - Any
Updated:4/21/2016
Start Date:February 2009
End Date:December 2015

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The Role of Serine-Proteases in Gastrointestinal Function and Irritable Bowel Syndrome

The proposed pilot project for this seed grant focuses on the role of intestinal
serine-proteases in the pathogenesis of diarrhea-predominant IBS (D-IBS). In this study we
will further assess serine-protease activity in patients with D-IBS and also explore a
possible mechanism by which these proteases can lead to alterations in intestinal physiology
and symptoms in these patients.

The general hypotheses for the proposed research are that (A) the levels of fecal
serine-protease in patients with D-IBS are abnormally increased (B) this abnormal
serine-protease activity leads to/is associated with an abnormal increase in intestinal
permeability and therefore enables (C) chronic stimulation and activation of the mucosal
immune system in these patients. In addition, it is aim to determine whither periodontal
inflammation is associated with intestinal permeability and serine protease activity.


Inclusion Criteria:

- Any sex, race, or ethnicity.

- At least 18 years of age (no upper age limit).

- D-IBS patients must meet Rome III criteria for IBS and must have been evaluated by a
physician to exclude other diseases that could explain the symptoms. For the latter,
patients self statement is acceptable (no official document is required).

- Participation in Dr. Whitehead's 'heterogeneity of IBS' and/or Dr. Ringel's
'intestinal inflammation in patients with D-IBS' research study.

Exclusion Criteria:

- Healthy controls must have no significant or recurring gastrointestinal symptoms.

- Patients and healthy controls should not have a serious, unstable medical condition.

- Patients and healthy controls must have had no gastrointestinal tract surgery other
than appendectomy or cholecystectomy.

- Patients and healthy controls must not be pregnant (by self-report). Pregnant women
will not be allowed to participate as pregnancy can affect gastrointestinal symptoms.

- Patients and healthy controls must not have a history of inflammatory bowel disease,
celiac disease, or other diagnosis that could explain chronic or recurring bowel
symptoms in IBS patients or controls.

- Patients and healthy controls should have no history of lactose malabsorption (by
self-report).

- Patients and healthy controls should have no history of clinical symptoms of acute
infections during the last 8 weeks prior to enrolment in the study.

- Patients and healthy controls should have no history of anti-inflammatory agents
including aspirin, non-aspirin, non-steroid anti-inflammatory (NSAID) or steroids in
the last four weeks prior to study enrollment.

- Patients should not intentionally consume probiotics or undergo antibiotic treatment
during the last 4 weeks prior to enrolment in the study. If the subject consumed any
of these medications, a washout period of 4 weeks will be required).

- Patients must have no history of fainting or light headedness during periods of
fasting.

- Patients must not have diabetes mellitus, or any similar conditions, that would cause
an adverse reaction to the sugar drink.
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