Crohn Disease, Inflammatory Bowel Diseases, Ulcerative Colitis
Conditions
Keywords
IBD, UC, CD
Brief summary
The clinical investigation aims to generate clinical data to support the use of Multispectral Optoacoustic Tomography (MSOT) in clinical practice, its inclusion in diagnostic guidelines and to support its reimbursement, specifically to * Further validate the application with respect to including ulcerative colitis patients * Prepare a study protocol for large-scale clinical validation study in inflammatory bowel disease (IBD) * Successfully execute the clinical validation study
Detailed description
The clinical investigation, EUPHORIA, will pave the way to establish Multispectral Optoacoustic Tomography (MSOT) technology for the non-invasive assessment of intestinal inflammation in patients. EUPHORIA will enable commercialization of the technology by finalizing technical improvements that will increase diagnostic outcome beyond what has been shown in a first feasibility study, will improve usability, prepare CE marking for the new device and validate clinical results in a large clinical investigation. Inflammatory bowel disease (IBD) is a chronic condition, posing significant burden to patients and health care systems. Patients suffer from a relapsing course of intestinal inflammation, and to date, there is no satisfying noninvasive diagnostic modality for monitoring disease activity. In a recent clinical study conducted by University Hospital Erlangen, MSOT, a technology developed by iThera Medical (ITM), has proven to be superior in diagnostic performance to other procedures.
Interventions
DIAGNOSTIC_TESTMultispectral Optoacoustic Tomography (MSOT)
cMSOT-2 system is indicated for measurement of the Multispectral Optoacoustic Tomography (MSOT) values in the bowel wall of patients with an established diagnosis of inflammatory bowel disease (IBD), specifically Crohn's Disease (CD) and Ulcerative Colitis (UC). The MSOT values provided may be used as an aid to the assessment of inflammatory disease activity in the bowel wall.
Sponsors
European Commission
iThera Medical GmbH
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Established diagnosis of UC or CD for at least three months prior to enrollment 2. Age ≥ 18 years 3. Indication for endoscopy according to institutes routine care 4. Written informed consent
Exclusion criteria
1. Stoma independent of localization, ileoanal pouch 2. Prior bowel surgery other than ileocecal resection, which potentially affects the study procedure by fundamentally changing bowel anatomy by removing the ROI (e.g. (partial) resection of the sigmoid, left sided colon) or repositioning the ROI to an inaccessible location (e.g. right-sided colectomy with transversostomy) 3. Indeterminate Colitis, irritable bowel syndrome (IBS) 4. Involvement of the upper gastrointestinal (GI) track only 5. Isolated proctitis 6. Complications, such as infectious enteritis, infectious colitis and infectious enterocolitis, abscess formation, intestinal obstruction, toxic megacolon 7. Tattoo in skin area of interest 8. Skin lesions, scar tissue or skin diseases affecting the area of imaging 9. Highly pigmented skin in the area of imaging (e.g. Fitzpatrick skin type V and VI) 10. The bowel wall is invisible in the Ultrasound image of the MSOT system 11. Medication leading to increased light sensitivity 12. Pregnant and breastfeeding women 13. Mental retardation of the patient with restriction of general judgment and awareness 14. Exclusion due to safety concerns of investigator (subject who has any condition, including any physical, psychological, or psychiatric condition, which in the opinion of the Investigator, would compromise the safety of the subject or the quality of the data and renders the subject an unsuitable candidate for the study)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Derivation Cohort: derive optimum diagnostic MSOT thresholds | 5-10 days | Derivation cohort: The primary endpoint of the derivation cohort is to derive optimum diagnostic MSOT thresholds based on receiver operating characteristics (ROC) analysis to distinguish endoscopic active disease from remission in Crohn's Disease (CD) or Ulcerative Colitis (UC) patients. |
| Validation cohort: re-assess the diagnostic accuracy of MSOT | 5-10 days | Validation cohort: The primary endpoint of the validation cohort is to re-assess the diagnostic accuracy of MSOT to distinguish endoscopic active disease from remission in an independent cohort. It will be considered successful if a lower 90% confidence of limit at least 75% of area under curve (AUC) is reached |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Validation Cohort: MSOT performance, diagnostic accuracy measures | through study completion, an average of 1 year | Further diagnostic accuracy measures (sensitivity, specificity, predictive values) of MSOT to distinguish endoscopic active disease from remission using the MSOT thresholds from the derivation cohort |
| Derivation Cohort: MSOT thresholds | 9-10 months | Derive MSOT thresholds using histology as a reference: receiver operating characteristics (ROC) analysis to distinguish histologic active disease from remission. |
| Derivation Cohort: MSOT performance, diagnostic accuracy measures | 9-10 months | Diagnostic accuracy measures (area under curve (AUC), sensitivity, specificity) of MSOT to distinguish endoscopic active disease from remission. |
| Derivation Cohort: MSOT performance, diagnostic accuracy | 9-10 months | Diagnostic accuracy of MSOT to distinguish histologic active disease from remission |
| Validation Cohort: MSOT performance, diagnostic accuracy | through study completion, an average of 1 year | Diagnostic accuracy (area under curve (AUC), sensitivity, specificity, predictive values) of MSOT to distinguish histologic active disease from remission using the MSOT thresholds from the derivation cohort. |
| Both cohorts: diagnostic accuracy | through study completion, an average of 1 year | Diagnostic accuracy of MSOT to distinguish clinical active disease from remission. |
| Both cohorts: performance of other non-invasive diagnostic modalities | through study completion, an average of 1 year | Assess performance of other non-invasive diagnostic modalities in order to allow for comparison to MSOT performance. Diagnostic accuracy of each of the various non-invasive tests (CRP, fCal, US, MRI) with respect to the endoscopy (reference test) and histology will be calculated using standard techniques for diagnostic studies. This includes cross tabulation of the index test results by the results of the reference standard, as well as plots of their distribution and ROC curves. Area under the Curve (AUC) estimates and confidence intervals (DeLong) will be calculated. Score confidence intervals (Wilson) will be calculated for proportions such as sensitivity, specificity, and predictive values at the predefined thresholds. |
| Both cohorts: interobserver variability | through study completion, an average of 1 year | Explore variations in MSOT diagnostic accuracy between sites and operators (interobserver variability). |
| Both cohorts: likelihood ratios and predictive values for active inflammation | through study completion, an average of 1 year | Assess the likelihood ratios and predictive values for active inflammation after MSOT examination. |
| Both cohorts: performance of MSOT in combination with other modalities | through study completion, an average of 1 year | Explore performance of MSOT in combination with other modalities, e.g. in combination with ultrasound (US) or laboratory. AUC will be estimated for all non-invasive tests with a 95% confidence interval (DeLong) both from the derivation cohort and from the pooled cohorts (derivation + validation) for increased precision. Cohen's κ will be used as a measure of overall agreement. Results will be presented in three-way tables, comparing the new test (MSOT), the non-reference standard (non-invasive modalities), and the reference standard (endoscopy). |
| Both cohorts: discriminate different grades of disease activity | through study completion, an average of 1 year | Investigate ability of MSOT and other non-invasive diagnostic modalities, i.e. ultrasoiund (US), fecal calprotectin (fCal), clinical scores to discriminate different grades of disease activity (remission, mild, moderate, high according to endoscopy, histology or clinical scores; for cut-offs. |
| Both cohorts: patient preference | 5-10 days | Evaluate patient preference for different tests using a patient survey |
| Derivation cohort: MSOT thresholds using clinical scores as a reference | through study completion, an average of 1 year | Derive MSOT thresholds using clinical scores as a reference: ROC analysis to distinguish clinical active disease from remission (only derivation cohort). |
Countries
Germany, Italy
Outcome results
None listed