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Host Immune Response to Clostridium Difficile Infection in Inflammatory Bowel Disease Patients

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ClinicalTrials.gov Identifier: NCT01813500
Recruitment Status : Completed
First Posted : March 19, 2013
Last Update Posted : April 26, 2017
Optimer Pharmaceuticals LLC
Information provided by (Responsible Party):
Francis Farraye, MD, Boston Medical Center

Brief Summary:

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.

Condition or disease Intervention/treatment
Crohn's Disease Ulcerative Colitis Clostridium Difficile Inflammatory Bowel Disease Other: Blood and stool sample

Detailed Description:

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.

Study Type : Observational
Actual Enrollment : 400 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Host Immune Response to Clostridium Difficile Infection in Inflammatory Bowel Disease Patients
Actual Study Start Date : October 2011
Primary Completion Date : September 2015
Study Completion Date : April 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bowel Movement
U.S. FDA Resources

Group/Cohort Intervention/treatment
IBD Patients
Subjects with Crohn's Disease or Ulcerative colitis. IBD patients will be asked to provide a blood and stool sample.
Other: Blood and stool sample
Subjects are asked to provide a blood sample (6 to 10cc) and a stool sample. An additional blood sample will be requested if the subject has a flare.
Control Subjects
Subjects without Crohn's Disease or Ulcerative Colitis. Controls will also be asked to provide a blood and stool sample.
Other: Blood and stool sample
Subjects are asked to provide a blood sample (6 to 10cc) and a stool sample. An additional blood sample will be requested if the subject has a flare.

Primary Outcome Measures :
  1. Colonization [ Time Frame: 12 Months ]
    Determine Clostridium colonization in IBD patients during clinical remission and during flares (including CD, UC and UC patients after IPAA) compared to controls

Secondary Outcome Measures :
  1. Incidence [ Time Frame: 12 months ]
    Determine the incidence of CDI in patients with IBD (including CD, UC and UC patients after IPAA) compared to controls and correlate to anti-toxin titer levels using the methods as outlined above

Biospecimen Retention:   Samples Without DNA
Serum, stool

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 and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Subjects with Crohn's Disease and Ulcerative Colitis or healthy controls.

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

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): NCT01813500

United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
Boston Medical Center
Optimer Pharmaceuticals LLC
Principal Investigator: Francis A Farraye, MD Boston Medical Center Department of Gastroenterology

Responsible Party: Francis Farraye, MD, Principal Investigator, Boston Medical Center
ClinicalTrials.gov Identifier: NCT01813500     History of Changes
Other Study ID Numbers: H-31226
First Posted: March 19, 2013    Key Record Dates
Last Update Posted: April 26, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Additional relevant MeSH terms:
Crohn Disease
Colitis, Ulcerative
Intestinal Diseases
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases