Crohn's Disease
Conditions
Keywords
capsule endoscopy, Crohn's disease, small bowel disease, inflammatory bowel disease, Patients with suspected small bowel Crohn's disease
Brief summary
The aim of this study is to validate the ability of Capsule Endoscopy (CE) to accurately diagnose small bowel (SB) Crohns disease in patients with symptoms of abdominal pain and diarrhea. The primary objective of the study is to evaluate whether Capsule Endoscopy prior to colonoscopy will improve diagnosis in patients with suspected Crohns disease when compared to standard diagnostic testing.
Detailed description
Crohn's disease is a chronic, inflammatory disorder (IBD) affecting any part of the gastrointestinal tract but frequently involves the small and large bowel. Typical presenting symptoms include abdominal pain and diarrhea. Patients with this disorder may also have extraintestinal manifestations including arthritis, uveitis and aphthous stomatitis, erythema nodosum and pyoderma gangrenosum. The etiology of Crohn's disease is unknown. It affects populations around the globe and occurs at any age but it has a predilection to affect those between the ages of 15 and 35. While about one half of patients have involvement of the ileum and large bowel, another third have disease isolated to the small bowel. Frequently, small bowel Crohn's disease can be difficult to diagnose using the traditional methods of evaluation including colonoscopy with ileoscopy and contrast radiography. Mucosal features of Crohn's disease are often subtle and difficult to identify by small bowel follow through (SBFT). The SBFT has traditionally been relied on to evaluate the small intestine for evidence of Crohn's disease but it has been shown to have a relatively low accuracy of only 30%. This has led to delays in the diagnosis of Crohn's disease with reports ranging from one to three years. In the past few years, capsule endoscopy has sparked renewed interest in the investigation of IBD and Crohn's disease of the small bowel. A PillCam™ SB2 capsule (Given Imaging Ltd, Yoqneam, Israel) is an ingestible, disposable video camera that transmits high quality images of the small intestinal mucosa. This enables the small intestine to be readily accessible to physicians investigating for the presence of small bowel disorders which in the past was inaccessible to physicians. A number of small pilot studies demonstrated capsule endoscopy efficacy in diagnosing SB Crohn's disease. Diagnostic yields of 70% have been reported in small series of studies performed in suspected small bowel Crohn's disease. This study is designed to determine the yield and clinical impact of Capsule Endoscopy (CE) in detecting suspected IBD and suspected Crohn's Disease of the small bowel when compared to SBFT.
Interventions
DEVICECapsule Endoscopy
Pillcam Platform with RAPID5 software and supporting SB2 capsules
Sponsors
Medtronic - MITG
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients ages 10-65 years, inclusive * Patient suffers from either * diarrhea for more than 6 weeks and less than 3 years and/or * abdominal pain for more than 6 weeks and less than 3 years and/or * extra-luminal manifestations of IBD including: erythema nodosum, pyoderma gangrenosum, arthritis, peri-anal disease, uveitis, aphthous stomatitis * Patient suffers from at least one of the symptoms / lab abnormalities listed below: * Positive inflammatory marker (ESR, CRP, thrombocytosis, leukocytosis, fecal lactoferrin, fecal alpha-1 antitrypsin) within 3 months prior to enrollment * Unexplained anemia (less than normal limits) within 3 months prior to enrollment * Hypoalbuminemia (\<3.5 g/dl) within 3 months of enrollment * Positive ASCA within 3 months of enrollment * Abnormal white blood cell scan with in 3 months of enrollment * Stool negative for O&P (C&S) within 3 months of enrollment * Recurrent Fevers * Unexplained weight loss, failure to thrive in children * Gastro-intestinal bleeding including melena and/or hematochezia and/or FOBT positive. * Chronic perianal disease (fistula, fissure, peri-rectal abscess) * Abnormal small bowel SBFT and/or enteroclysis and/or abdominal CT not conclusively diagnostic for IBD * Patient is indicated for Ileo-Colonoscopy * Patient or legal guardian agrees to sign consent form
Exclusion criteria
* Indeterminate Colitis where the purpose is only to make a definitive diagnosis and where the inclusion criteria are not otherwise met * Known intestinal obstruction or current obstructive symptoms, such as severe abdominal pain with accompanying nausea or vomiting. * Definite long stricture seen on radiological exam. * Suspected GI stricture, followed by agile™ study that could not prove patency of the GI tract. * Known history of small bowel Crohn's Disease * Current treatment for active IBD * Positive Anti-tTG or anti-endomysial antibody * Any of the following work-up within 1 year of study entry: Capsule Endoscopy, Colonoscopy and Upper GI/SBFT. * Non-steroidal anti-inflammatory drugs including Aspirin, (twice weekly or more) during the 4 weeks preceding enrollment * Patient is pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic Yield in Suspected Crohn's Patients (CE Prior to IC vs. IC and SBFT) | four months from enrollment | To evaluate whether capsule endoscopy (CE) prior to ileocolonoscopy (IC) improves the diagnostic yield in patients with suspected Crohn's disease when compared to IC and SBFT. McNemar test was preformed in order to evaluate the diagnostic yield of IC combined with CE as compared to the diagnostic yield of IC combined with SBFT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic Yield (CE vs. SBFT) | four months from enrollment | McNemar test was preformed in order to evaluate the diagnostic yield of PillCam SB (CE) as compared to the diagnostic yield of small bowel follow through (SBFT). |
| Diagnostic Yield (CE vs. IC) | four months from enrollment | McNemar test was preformed in order to evaluate the diagnostic yield of PillCam SB (CE) as compared to the diagnostic yield of ileocolonoscopy (IC). |
Countries
Canada, Israel, Sweden, United States
Participant flow
Recruitment details
Study started on September 2007 and data collection completed on October 2010. Study conducted in 10 clinical sites (hospitals and private clinics) in the USA, Sweden, Canada and Israel
Pre-assignment details
98 patients enrolled in this study. 18 cases excluded due to the following: 15 cases were excluded due to noncompliance with the protocol. 1 patient withdrew consent before any study procedure. 1 patient could not ingest the capsule. 1 patient refused to undergo the ileocolonoscopy and SBFT. Therefore 80 patients were included in the analysis
Participants by arm
| Arm | Count |
|---|---|
| SB Capsule Then Standard Ileocolonoscopy Capsule endoscopy was ingested.The purpose was to detect patients with Crohn's Disease. Patients subsequently had standard ileocolonoscopy and small bowel follow through as comparison. | 80 |
| Total | 80 |
Baseline characteristics
| Characteristic | SB Capsule Then Standard Ileocolonoscopy |
|---|---|
| Age, Categorical <=18 years | 20 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 60 Participants |
| Age, Continuous | 28.35 years STANDARD_DEVIATION 13.25 |
| Region of Enrollment Israel | 20 participants |
| Region of Enrollment Sweden | 14 participants |
| Region of Enrollment United States | 46 participants |
| Sex: Female, Male Female | 38 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 80 |
| other Total, other adverse events | 8 / 80 |
| serious Total, serious adverse events | 1 / 80 |
Outcome results
Primary
Diagnostic Yield in Suspected Crohn's Patients (CE Prior to IC vs. IC and SBFT)
To evaluate whether capsule endoscopy (CE) prior to ileocolonoscopy (IC) improves the diagnostic yield in patients with suspected Crohn's disease when compared to IC and SBFT. McNemar test was preformed in order to evaluate the diagnostic yield of IC combined with CE as compared to the diagnostic yield of IC combined with SBFT.
Time frame: four months from enrollment
Population: The number of found and missed pathologies (i.e. ulcers, lesions, etc.) were calculated for the combination of procedures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PillCam SB Followed by Ileo Colonoscopy | Diagnostic Yield in Suspected Crohn's Patients (CE Prior to IC vs. IC and SBFT) | 97.3 percentage of yield |
| Small Bowel Follow Through (SBFT) and Ileo-colonoscopy | Diagnostic Yield in Suspected Crohn's Patients (CE Prior to IC vs. IC and SBFT) | 57.3 percentage of yield |
Comparison: Pathologies were including in the analysis as follows:~* combination of CE+IC procedures but not detected by the combination of SBFT+IC procedures were marked as CE+IC new finding ;~* Pathologies detected by the combination of SBFT+IC procedures but not detected by the combination of CE+IC procedures were marked as SBFT+IC new finding event;~* Pathologies detected by the combination of CE+IC procedures and by the combination of SBFT+IC procedures were marked as same findings event.p-value: <0.0001McNemar
Secondary
Diagnostic Yield (CE vs. IC)
McNemar test was preformed in order to evaluate the diagnostic yield of PillCam SB (CE) as compared to the diagnostic yield of ileocolonoscopy (IC).
Time frame: four months from enrollment
Population: The number of found and missed pathologies (i.e. ulcers, lesions, etc.) were calculated for the combination of procedures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PillCam SB Followed by Ileo Colonoscopy | Diagnostic Yield (CE vs. IC) | 49.2 percentage of yield |
| Small Bowel Follow Through (SBFT) and Ileo-colonoscopy | Diagnostic Yield (CE vs. IC) | 70.5 percentage of yield |
Comparison: Pathologies were including in the analysis as follows:~* Pathologies detected by CE procedure but not detected by IC procedure were marked as CE new finding event;~* Pathologies detected by IC procedure but not detected by CE procedure were marked as IC new finding event;~* Pathologies detected by both procedures (i.e., CE and IC) were marked as same findings event.p-value: 0.085McNemar
Secondary
Diagnostic Yield (CE vs. SBFT)
McNemar test was preformed in order to evaluate the diagnostic yield of PillCam SB (CE) as compared to the diagnostic yield of small bowel follow through (SBFT).
Time frame: four months from enrollment
Population: The number of found and missed pathologies (i.e. ulcers, lesions, etc.) were calculated for the combination of procedures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PillCam SB Followed by Ileo Colonoscopy | Diagnostic Yield (CE vs. SBFT) | 93.0 percentage of yield |
| Small Bowel Follow Through (SBFT) and Ileo-colonoscopy | Diagnostic Yield (CE vs. SBFT) | 25.6 percentage of yield |
Comparison: For each category, the numbers of found and missed pathologies were including in the analysis as follows:~* Pathologies detected by CE procedure but not detected by SBFT procedure were marked as CE new finding event;~* Pathologies detected by SBFT procedure but not detected by CE procedure were marked as SBFT new finding event;~* Pathologies detected by both procedures (i.e., CE and SBFT) were marked as same findings event.p-value: <0.0001McNemar