Crohn Disease
Conditions
Keywords
Irritable Bowel Disease, IBD, Mucosal Disease, Crohn's, Inflammatory Bowel Disease
Brief summary
This study will evaluate the efficacy of capsule endoscopy (CE) versus ileocolonoscopy (IC) plus MRE for detection of active Crohn's disease (CD) in the small bowel in subjects with known CD and mucosal disease. The primary objective of the study is to assess the accuracy of CE versus IC plus MRE for detecting active CD, by visualizing the small bowel and colon in subjects with known CD and mucosal disease. There will be assessment of mucosal disease activity at baseline. Patient satisfaction questionnaire will be completed at baseline.
Detailed description
This is a multicenter, prospective, study, evaluating the efficacy of CE versus IC plus MRE for detecting active Crohn's Disease (CD) in the small bowel and colon in subjects with known CD and mucosal disease. A screening visit will be performed within 30 days prior to baseline procedures to assess pre-procedure eligibility. At this visit the following assessments will be performed: Informed Consent, Inclusion/Exclusion Criteria, Demographics, Montreal Classification, Medical History, Previous GI procedures, Surgical history, Laboratory tests and pregnancy tests. At baseline, subjects with known CD on routine evaluation (e.g. history, physical exams, labs) and a recent history of mucosal disease (within the last 2 years and diagnosis based on radiologic, endoscopic, or histologic findings) OR subjects with known CD and active disease based on clinical judgment based on symptoms, laboratory data or other clinical information will undergo Magnetic Resonance Enterography (MRE), Capsule Endoscopy (CE) and Ileocolonoscopy (IC), to assess presence or absence of CD across the small and large bowel. Also, at baseline the following assessments will take place: Laboratory tests, Pregnancy test, Concomitant medications, Patient satisfaction questionnaire and Adverse Events (AE). Subjects will be exited from the study once all Baseline Procedures have been completed and AEs resolved. All CE videos, IC videos and MRE images will be evaluated by central readers. The planned number of subjects is 352. Subjects will be enrolled at up to 40 sites in the United States, Israel, and Austria. Study duration is expected to be up to approximately 1.5 years. The expected duration of each subject's participation is approximately 1 month.
Interventions
DEVICECapsule Endoscopy
At baseline subject will under the PillCam Crohn's Capsule Procedure
Sponsors
Medtronic - MITG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has provided informed consent. * Subject is ≥ 18 years of age * Subject is willing and able to comply with all aspects of treatment and evaluation schedule. * Subject has known CD and a recent history (within last 2 years) of mucosal disease (based on radiologic, endoscopic, or histologic evidence) OR known CD and active disease, based on clinical judgment based on symptoms, laboratory data or other clinical information.
Exclusion criteria
* Subject has indeterminate, ulcerative, antibiotic-associated colitis. * Subject has stool positive for ova and parasite and for Clostridium difficile toxins within 3 months prior to enrollment. * Subject with other known infectious cause of abdominal symptoms. * Subject with clinical evidence of renal disease with the past 6 months, defined as estimated glomerular filtration rate (GFR) outside the normal reference range. * Subject with known history of intestinal obstruction or current obstructive symptoms, such as severe abdominal pain with accompanying nausea or vomiting, based on investigator judgment. * Subject with a diagnosis of gastroparesis or small bowel or large bowel dysmotility. * Subject with suspected or known bowel obstruction, stricture (defined as unequivocal proximal upstream dilation equal ≥ 2.5 cm), or fistula. * Subject has used non-steroidal anti-inflammatory drugs including aspirin, two times per week, during the 4 weeks preceding enrollment. Low dose aspirin regimens (≤ 100 mg daily) are acceptable and not exclusionary. * Subject suffers from any condition, such as swallowing problems, that precludes compliance with study and/or device instructions. * Subject with cardiac pacemaker or other implanted electromedical device. * Subject has an allergy or other known contraindication to the medications used in the study. * Subject is pregnant (documented by a positive pregnancy test) or is actively breast-feeding. * Subject is considered to be a part of a vulnerable population (eg. prisoners or those without sufficient mental capacity). * Subject has a known contraindication to MRE or IC. * Subject has participated in a drug or device research study within 30 days of enrollment that may interfere with the subject's safety or ability to participate in the study. * Subject has any medical condition that would make it unsafe for them to participate, per Investigator's discretion * Subject with ileostomy or colostomy, history of total or subtotal colectomy (including those with ileosigmoidostomy, and ileorectostomy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Accuracy of CE Versus IC Plus MRE for Detecting Active Crohn's Disease (CD), by Visualizing the Small Bowel and Colon in Subjects With Know CD and Mucosal Disease. | Baseline | Central readers will be used to read all videos/images and analyses will be based on these results. A consensus panel will be used if there are discrepancies in results between modalities at baseline. Capsule endoscopy and IC results will be read by gastroenterologists and MRE results will be read by radiologists. Scores used will be Lewis Score, Simple Endoscopic Score for Crohn's Disease Index (SES-CD) Score and Magnetic Resonance Index of Activity (MaRIA) Score |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Specificity, Negative Predictive Value, and Positive Predictive Value for Active CD in the Small Bowel and Colon by CE as Compared to IC Plus MRE. | Baseline | Central readers will be used to read all videos/images and analyses will be based on these results. A consensus panel will be used if there are discrepancies in results between modalities at baseline. Capsule endoscopy and IC results will be read by gastroenterologists and MRE results will be read by radiologists. Scores used will be Lewis Score, Simple Endoscopic Score for Crohn's Disease Index (SES-CD) Score and Magnetic Resonance Index of Activity (MaRIA) Score |
| Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | Baseline | Central readers will be used to read all videos/images and analyses will be based on these results. A consensus panel will be used if there are discrepancies in results between modalities at baseline. Capsule endoscopy and IC results will be read by gastroenterologists and MRE results will be read by radiologists. Scores used will be Lewis Score, Simple Endoscopic Score for Crohn's Disease Index (SES-CD) Score and Magnetic Resonance Index of Activity (MaRIA) Score |
| Patient Satisfaction | After completion of final procedure, either the same day or by the next business day following procedure completion. | Patient preference of which procedure they preferred (CE, IC or MRE plus IC) |
Countries
Austria, Israel, United States
Participant flow
Recruitment details
187 subjects signed consent. Per the protocol, a subject was not considered enrolled until consent was signed and subject met inclusion/exclusion criteria. Of the 187 who signed consent, 158 were considered enrolled per the protocol. 29 were screen failures, i.e. they signed informed consent, but ended up failing inclusion/exclusion.
Pre-assignment details
Of the 187 subjects who signed informed consent, 29 failed inclusion/exclusion criteria and were exited from the study. Criteria included labs, which caused some subjects to wash out at this early phase. This left us with 158 subjects. For various reasons, 39 additional subjects were exited prior to all imaging procedures being completed.
Participants by arm
| Arm | Count |
|---|---|
| MRE, Patency Capsule (if Needed), CE, and IC Subjects will undergo MRE, patency capsule (if necessary), CE, and IC procedures.
If MRE shows evidence of a stricture, subject must undergo a Patency procedure prior to CE. If patency cannot be confirmed through MRE or patency capsule will be discontinued from the study.
Subjects will perform bowel preparation and follow a detailed dietary regimen for CE and IC procedures. Between 45 and 75 minutes after final PEG ingestion, subject will swallow the PillCam Crohn's Capsule. Adequate boosts will be administered, as necessary. Subjects will be allowed to leave clinic after 'Alert 2' is received and if capsule is not yet excreted. Subjects leaving prior to excretion will be instructed to disconnect the recorder at excretion or battery failure (whichever is first).
After CE procedure (either same or following day), subject will undergo IC. If the IC is done the following day, subject will stay on clear liquid diet (or NPO, per physician's discretion for sedation). | 99 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | MRE Stricture or Patency Capsule Failure | 25 |
| Overall Study | Physician Decision | 6 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | MRE, Patency Capsule (if Needed), CE, and IC | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 3 Participants | — |
| Age, Categorical Between 18 and 65 years | 96 Participants | — |
| BMI | 28.82 kg/m² STANDARD_DEVIATION 7.36 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Austria | 2 participants | — |
| Region of Enrollment Israel | 2 participants | — |
| Region of Enrollment United States | 95 participants | — |
| Sex: Female, Male Female | 63 Participants | — |
| Sex: Female, Male Male | 36 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 119 |
| other Total, other adverse events | 11 / 119 |
| serious Total, serious adverse events | 7 / 119 |
Outcome results
Primary
Accuracy of CE Versus IC Plus MRE for Detecting Active Crohn's Disease (CD), by Visualizing the Small Bowel and Colon in Subjects With Know CD and Mucosal Disease.
Central readers will be used to read all videos/images and analyses will be based on these results. A consensus panel will be used if there are discrepancies in results between modalities at baseline. Capsule endoscopy and IC results will be read by gastroenterologists and MRE results will be read by radiologists. Scores used will be Lewis Score, Simple Endoscopic Score for Crohn's Disease Index (SES-CD) Score and Magnetic Resonance Index of Activity (MaRIA) Score
Time frame: Baseline
Population: Per-protocol analysis set, includes subjects who underwent MRE, CE, and IC (and could be evaluated for CD activity) who had no major deviations (violations that may have significant impact on outcomes) and did not meet following criteria:~* Subject withdraws~* Capsule remained in stomach or small bowel for entire procedure~* Technical failure
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MRE, Patency Capsule (if Needed), CE, and IC | Accuracy of CE Versus IC Plus MRE for Detecting Active Crohn's Disease (CD), by Visualizing the Small Bowel and Colon in Subjects With Know CD and Mucosal Disease. | Sensitivity CE Overall | 94 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Accuracy of CE Versus IC Plus MRE for Detecting Active Crohn's Disease (CD), by Visualizing the Small Bowel and Colon in Subjects With Know CD and Mucosal Disease. | Sensitivity MRE + IC Overall | 100 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Accuracy of CE Versus IC Plus MRE for Detecting Active Crohn's Disease (CD), by Visualizing the Small Bowel and Colon in Subjects With Know CD and Mucosal Disease. | Specificity CE Overall | 74 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Accuracy of CE Versus IC Plus MRE for Detecting Active Crohn's Disease (CD), by Visualizing the Small Bowel and Colon in Subjects With Know CD and Mucosal Disease. | Specificity MRE + IC Overall | 22 percentage of participants |
Comparison: This was a 1-arm, non-powered study. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) was estimated for each treatment group, along with the 95% confidence interval. The difference between treatment groups in Sensitivity and Specificity was compared.p-value: 0.125McNemar
Secondary
Patient Satisfaction
Patient preference of which procedure they preferred (CE, IC or MRE plus IC)
Time frame: After completion of final procedure, either the same day or by the next business day following procedure completion.
Population: Subjects who completed the satisfaction questionnaire and underwent all 3 procedures MRE, CE, and IC and could be evaluated for overall active CD at baseline (i.e., a modified intent-to-treat (mITT).~population).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MRE, Patency Capsule (if Needed), CE, and IC | Patient Satisfaction | Preferred PillCam CE | 64 Participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Patient Satisfaction | Preferred IC | 43 Participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Patient Satisfaction | Preferred MRE + IC | 11 Participants |
Secondary
Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE
Central readers will be used to read all videos/images and analyses will be based on these results. A consensus panel will be used if there are discrepancies in results between modalities at baseline. Capsule endoscopy and IC results will be read by gastroenterologists and MRE results will be read by radiologists. Scores used will be Lewis Score, Simple Endoscopic Score for Crohn's Disease Index (SES-CD) Score and Magnetic Resonance Index of Activity (MaRIA) Score
Time frame: Baseline
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | Sensitivity CE Proximal Small Bowel (PSB) | 97 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | Sensitivity MRE PSB | 71 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | Specificity CE PSB | 87 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | Specificity MRE PSB | 66 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | NPV CE PSB | 98 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | NPV MRE PSB | 83 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | PPV CE PSB | 77 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | PPV MRE PSB | 49 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | Sensitivity CE Terminal ilium (TI) | 94 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | Sensitivity MRE + IC TI | 98 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | Specificity CE TI | 82 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | Specificity MRE + IC TI | 37 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | NPV CE TI | 91 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | NPV MRE + IC TI | 93 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | PPV CE TI | 88 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | PPV MRE + IC TI | 68 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | Sensitivity CE Colon | 83 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | Sensitivity IC Colon | 91 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | Specificity CE Colon | 88 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | Specificity IC Colon | 89 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | NPV CE Colon | 93 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | NPV IC Colon | 97 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | PPV CE Colon | 70 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Sensitivity, Specificity, Negative Predictive Value and Positive Predictive Value for Active CD in Designated Bowel Segments (Proximal Small Bowel Terminal Ileum, and Colon) by Capsule Endoscopy as Compared to IC Plus MRE | PPV IC Colon | 75 percentage of participants |
Secondary
Specificity, Negative Predictive Value, and Positive Predictive Value for Active CD in the Small Bowel and Colon by CE as Compared to IC Plus MRE.
Central readers will be used to read all videos/images and analyses will be based on these results. A consensus panel will be used if there are discrepancies in results between modalities at baseline. Capsule endoscopy and IC results will be read by gastroenterologists and MRE results will be read by radiologists. Scores used will be Lewis Score, Simple Endoscopic Score for Crohn's Disease Index (SES-CD) Score and Magnetic Resonance Index of Activity (MaRIA) Score
Time frame: Baseline
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MRE, Patency Capsule (if Needed), CE, and IC | Specificity, Negative Predictive Value, and Positive Predictive Value for Active CD in the Small Bowel and Colon by CE as Compared to IC Plus MRE. | Specificity | 74 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Specificity, Negative Predictive Value, and Positive Predictive Value for Active CD in the Small Bowel and Colon by CE as Compared to IC Plus MRE. | Negative Predictive Value (NPV) | 83 percentage of participants |
| MRE, Patency Capsule (if Needed), CE, and IC | Specificity, Negative Predictive Value, and Positive Predictive Value for Active CD in the Small Bowel and Colon by CE as Compared to IC Plus MRE. | Positive Predictive Value (PPV) | 91 percentage of participants |