Prospective study to compare in a blinded fashion four different diagnostic modalities to
detect active small bowel Crohn's disease: a) colonoscopy with ileoscopy; b) small bowel
follow through; c) capsule endoscopy; and d) computed tomography enterography.
The aims of this study are as follows: 1) to describe the spectrum of small intestinal
lesions demonstrated by capsule endoscopy (CE) in patients with Crohn's disease; 2) to
determine the inter-observer agreement for recognizing these small intestinal lesions; 3) to
determine the sensitivity, positive predictive value, and accuracy of CE, CT enterography,
small bowel follow-through, colonoscopy with ileoscopy, and all pairwise combinations of
these examinations with a consensus clinical diagnosis for the diagnosis and evaluation of
the extent and severity of small intestinal Crohn's disease; 4) to establish a Crohn's
Disease Capsule Endoscopy Index of Severity (CDCEIS); 5) to describe the spectrum of right
colon lesions demonstrated by CE in patients with Crohn's disease.
Study Design and Methods:
Consecutive adult patients with suspected or definite Crohn's disease seen in the
Inflammatory Bowel Disease Clinic at Mayo Clinic Rochester will be offered enrollment in a
prospective observational trial comparing CE with CT enterography, small bowel
follow-through, colonoscopy, and a consensus clinical diagnosis of Crohn's disease. Seventy
patients will be enrolled, according to the inclusion and exclusion criteria, and written
informed consent will be obtained. Co-investigators in the Inflammatory Bowel Disease (IBD)
Clinic will clinically evaluate all patients, including a history and limited physical
examination. Patients will undergo clinically indicated laboratory tests. Serum will be
stored on all patients for other potential laboratory studies. Patients will complete a
retrospective symptom diary for the week prior to their evaluation at Mayo, and a Crohn's
Disease Activity Index (CDAI) will be calculated.
All patients will have a CT enterography with peroral contrast interpreted by a
co-investigator radiologist. All patients will undergo a clinically indicated colonoscopy
with ileoscopy by a staff co-investigator (not by C.A.S. or the staff co-investigator
interpreting the CE), and a Crohn's Disease Endoscopic Index of Severity (CDEIS) will be
calculated. If no significant small bowel strictures are identified by CT enterography or
colonoscopy with ileoscopy, then patients will subsequently undergo CE. All CE studies will
be read separately by C.A.S. (gastroenterology fellow) and a supervising staff
gastroenterologist co-investigator, each blinded to the other's interpretation. The
interobserver agreement between C.A.S. and the co-investigator staff will be determined.
Patients will lastly have a clinically indicated small bowel follow-through interpreted by a
co-investigator radiologist. All co-investigators will be blinded to the results of the
other imaging modalities until after interpreting their respective studies.
Following each imaging procedure, the interpreting physician will complete both small
intestine and colon anatomy forms. The physician will identify all types of lesions present
and also give both a global evaluation of the severity of lesions found and a global Crohn's
disease activity score indicating one of the following: active Crohn's disease, suspicious
for Crohn's disease, inactive Crohn's disease, or no evidence of Crohn's disease.
Co-investigators representing each of the diagnostic modalities will meet periodically to
review those cases where there is disagreement among the imaging procedures with respect to
the extent and severity of small intestinal Crohn's disease in order to reach a consensus
clinical diagnosis. This consensus clinical diagnosis will serve as the gold standard
against which each of the individual imaging modalities is evaluated. Sensitivity, positive
predictive value, and accuracy of all diagnostic modalities compared to the consensus
clinical diagnosis will be determined. A Crohn's disease capsule endoscopy index of severity
(CDCEIS) will be created after the CE studies have been reviewed by investigators from other
referral centers both inside and outside the United States to determine the inter-observer
agreement (reproducibility) for each type of small bowel lesion identified by CE. Logistic
regression analysis with step-wise deletion will then be utilized to create the CDCEIS using
only those lesions that are reproducible, with the global Crohn's disease endoscopic
activity score from the CE as the dependent variable.
- Outpatient of either sex aged 18 to 70 years
- Patient has suspected or definite Crohn's disease
- Patient has read, understood, and signed a written informed consent form at visit 1.
- Patients who are prisoners, institutionalized individuals, or vulnerable adults
- Patients immediately in need of abdominal surgery for active gastrointestinal
bleeding, peritonitis, intestinal obstruction, perforation, or intra-abdominal
- Patients with known or suspected gastrointestinal obstruction due to significant
stricture based upon the clinical symptoms (nausea, vomiting, abdominal distention,
or abdominal pain) confirmed by pre-procedure evaluation. Pre-procedure evaluation
includes CT enterography or small bowel follow through performed at Mayo or
previously at an outside institution which demonstrates mechanical obstruction
(mechanical obstruction defined as small bowel narrowing with pre-stenotic
dilatation); additionally, a high-grade stenotic ileocecal valve or ileocolonic
anastomosis found by colonoscopy.
- Patients with history of abdominal radiation
- Patients with known or suspected oropharyngeal or esophageal dysphagia (unless recent
EGD shows no evidence of mechanical obstruction of the esophagus, in cases of
- Patients with pacemakers or other implantable electromedical devices
- Patients with highly suspected or documented gastroparesis
- Patients who have used NSAIDs within the previous 2 weeks
- Patients with an anticipated need for an MRI scan within two weeks after M2A capsule
ingestion (for patients who require a clinically indicated MRI, the MRI should be
performed prior to administration of the M2A capsule)
- Patients with a creatinine ≥ 2.0.
- Patients with documented reaction to iodinated contrast material.
- Patients with an ileostomy or colostomy
- Patients with documented reaction to metoclopramide.
- Patients with a hemoglobin less than 7.5 g/dl. (Patients with Crohn's disease are
often chronically anemic, and a hemoglobin of 7.5 g/dl or greater would allow these
patients to safely participate in the study.)