Host Immune Response to Clostridium Difficile Infection in Inflammatory Bowel Disease Patients
| Status: | Completed |
|---|---|
| Conditions: | Colitis, Irritable Bowel Syndrome (IBS), Infectious Disease, Gastrointestinal, Crohns Disease |
| Therapuetic Areas: | Gastroenterology, Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/27/2017 |
| Start Date: | October 2011 |
| End Date: | April 2016 |
The inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD) are
chronic conditions affecting approximately 1.4 million Americans. The burden of Clostridium
difficile infection (CDI), a frequent cause of infectious diarrhea is mediated by toxins A
and B and is increasing faster in IBD patients, than the general population. Clinically, CDI
in patients with IBD leads to a range of clinical syndromes from symptomless carriage, to
severe life threatening colitis, colectomy and death.
This pilot study will look at the relationship between IBD and this variable host immune
response. Clostridium difficile colonization (asymptomatic carrier state) is lower in the
IBD population than in the general population. In the general population, high antitoxin
titers have been linked with colonization and low antitoxin titers with recurrent disease.
The investigators hypothesize that patients with IBD will have a lower Clostridium difficile
colonization and will have lower antibody titers than the control group. Additionally those
with lower titers will have an increased risk of developing CDI.
In Aim 1 the investigators will determine Clostridium colonization in IBD subjects by stool
study (including CD, UC and UC patients after IPAA) compared to non-IBD subjects (controls).
In Aim 2 the investigators will compare antitoxin titers in these IBD subjects compared to
controls. In Aim 3 the investigators will follow these subjects for 12 months and calculate
the incidence of CDI in patients with IBD compared to controls and associations with
anti-toxin titers.
chronic conditions affecting approximately 1.4 million Americans. The burden of Clostridium
difficile infection (CDI), a frequent cause of infectious diarrhea is mediated by toxins A
and B and is increasing faster in IBD patients, than the general population. Clinically, CDI
in patients with IBD leads to a range of clinical syndromes from symptomless carriage, to
severe life threatening colitis, colectomy and death.
This pilot study will look at the relationship between IBD and this variable host immune
response. Clostridium difficile colonization (asymptomatic carrier state) is lower in the
IBD population than in the general population. In the general population, high antitoxin
titers have been linked with colonization and low antitoxin titers with recurrent disease.
The investigators hypothesize that patients with IBD will have a lower Clostridium difficile
colonization and will have lower antibody titers than the control group. Additionally those
with lower titers will have an increased risk of developing CDI.
In Aim 1 the investigators will determine Clostridium colonization in IBD subjects by stool
study (including CD, UC and UC patients after IPAA) compared to non-IBD subjects (controls).
In Aim 2 the investigators will compare antitoxin titers in these IBD subjects compared to
controls. In Aim 3 the investigators will follow these subjects for 12 months and calculate
the incidence of CDI in patients with IBD compared to controls and associations with
anti-toxin titers.
This is a two part pilot study, with the initial phase (Aim 1 and Aim 2) being a
cross-sectional epidemiological analysis of Clostridium difficile colonization and
anti-toxin antibodies in the IBD population compared to non-IBD patients.
The second phase (Aim 3) is a pilot nested case-control study that will follow both groups
of patients prospectively for 12 months to see who develops either colonization or active
CDI and correlate these to clinical demographics and serum Clostridium difficile anti-toxin
antibodies.
All subjects age eighteen and older who are able to give consent, have a diagnosis of
inflammatory bowel disease (see clinical definition of IBD below) and are followed in the
Center for Digestive Disease (CDD) are eligible for this study. Control subjects will also
be followed in the CDD without a diagnosis of IBD. All subjects will be recruited from
routine scheduled visits when seen as outpatients at the CDD or will be identified from the
inpatient Gastroenterology consult service or at the Internal Medicine Department at Shapiro
as part of Dr. Qazi's rotation(see recruitment section).
Subjects will be recruited in a block fashion to minimize confounding variables and ensure
groups with equal amount of diarrhea and to keep a 3:1 ratio of IBD to controls. Subject
will be recruited on a consecutive basis in a block of 32 slots. Within that block, 8 slots
will be for the control group (4 with diarrhea, 4 without) and 24 IBD patients (12 with
diarrhea, 12 without). Once all slots are filled then the next block will begin.
For Aim 1 and Aim 2: Upon enrollment subjects from both groups will provide blood and stool
samples (details of amount and timing discussed below) and a retrospective chart review will
document pre-determined data (as listed below). Total time requirement upon enrollment would
be about 10-15 minutes.
For Aim 3: This is an intention-to-treat analysis; control subjects who become diagnosed
with IBD during the study period will be kept in the control group. Patients will be
followed for a 12 month period:
If during that time there is no CDI then there will be no further study visits, only data
review at the end of the study period.
If a subject develops diarrhea in either group, treatment will be per standard of care
(detailed below) and research team will be alerted by primary Gastroenterologist or GI
consult team. If deemed appropriate by clinical team stool will be sent for C diff (per SOC)
and if positive, then repeat blood samples for anti-toxin titers may be collected (for
research purposes). At the end of the 12 month study period data will be reviewed.
cross-sectional epidemiological analysis of Clostridium difficile colonization and
anti-toxin antibodies in the IBD population compared to non-IBD patients.
The second phase (Aim 3) is a pilot nested case-control study that will follow both groups
of patients prospectively for 12 months to see who develops either colonization or active
CDI and correlate these to clinical demographics and serum Clostridium difficile anti-toxin
antibodies.
All subjects age eighteen and older who are able to give consent, have a diagnosis of
inflammatory bowel disease (see clinical definition of IBD below) and are followed in the
Center for Digestive Disease (CDD) are eligible for this study. Control subjects will also
be followed in the CDD without a diagnosis of IBD. All subjects will be recruited from
routine scheduled visits when seen as outpatients at the CDD or will be identified from the
inpatient Gastroenterology consult service or at the Internal Medicine Department at Shapiro
as part of Dr. Qazi's rotation(see recruitment section).
Subjects will be recruited in a block fashion to minimize confounding variables and ensure
groups with equal amount of diarrhea and to keep a 3:1 ratio of IBD to controls. Subject
will be recruited on a consecutive basis in a block of 32 slots. Within that block, 8 slots
will be for the control group (4 with diarrhea, 4 without) and 24 IBD patients (12 with
diarrhea, 12 without). Once all slots are filled then the next block will begin.
For Aim 1 and Aim 2: Upon enrollment subjects from both groups will provide blood and stool
samples (details of amount and timing discussed below) and a retrospective chart review will
document pre-determined data (as listed below). Total time requirement upon enrollment would
be about 10-15 minutes.
For Aim 3: This is an intention-to-treat analysis; control subjects who become diagnosed
with IBD during the study period will be kept in the control group. Patients will be
followed for a 12 month period:
If during that time there is no CDI then there will be no further study visits, only data
review at the end of the study period.
If a subject develops diarrhea in either group, treatment will be per standard of care
(detailed below) and research team will be alerted by primary Gastroenterologist or GI
consult team. If deemed appropriate by clinical team stool will be sent for C diff (per SOC)
and if positive, then repeat blood samples for anti-toxin titers may be collected (for
research purposes). At the end of the 12 month study period data will be reviewed.
Inclusion Criteria:
1. All subjects must be 18 years of age or older, able to provide written informed
consent, and able to comply with the requirements of the study.
2. All subjects must speak English. Non-English subjects are not included because of
lack of funding for interpreter services and clinical resources could not be used for
research purposes.
3. For Control Group only: Non-IBD subject seen in CDD during routine visit or on
inpatient consult service
4. For IBD Group Only: Chart history of IBD (either UC or CD) confirmed by colonoscopy,
pathology or gastroenterology clinical judgment
Exclusion Criteria:
1. Any subject planning on moving out of the area in the next year
2. Any patient not able to give informed consent
3. Any subject unwilling or not able to give stool sample upon enrollment
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