Enhancing Ultrasound & Photoacoustic for Recognition of Intestinal Abnormalities

Ulcerative Colitis Clinical Trial

— EUPHORIA  

Official title:

Enhancing Ultrasound & Photoacoustic for Recognition of Intestinal Abnormalities (EUPHORIA)

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04456400
• Other study ID #: cMSOT-2
• Status: Suspended
• Start date: February 3, 2021
• Est. completion date: April 2024

Study information

• Verified date: March 2023
• Source: iThera Medical GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 540
• Est. completion date: April 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Crohn Disease
• Inflammatory Bowel Diseases
• Ulcerative Colitis

Intervention

Diagnostic Test:
• Multispectral 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.

Locations

Country	Name	City	State
Germany	Charité- Universitätsmedizin Berlin, Campus Benjamin Franklin, Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Hindenburgdamm 30	Berlin
Germany	Universitätsklinikum Erlangen Medizinische Klinik 1	Erlangen
Germany	Universitätsklinikum Jena	Jena
Italy	I.R.C.C.S.San Raffaele, Gastroenterology and Gastrointestinal Endoscopy, Via Olgettina 60	Milan
Italy	Policlinico Tor Vergata	Roma	Lazio
Italy	Centro per la Ricerca e la Cura delle Malattie Infiammatorie Croniche Intestinali IRCCS Humanitas	Rozzano	Lombardia

Sponsors (2)

Lead Sponsor	Collaborator
iThera Medical GmbH	European Commission

Countries where clinical trial is conducted

Germany,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Derivation Cohort: derive optimum diagnostic MSOT thresholds	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.	5-10 days
Primary	Validation cohort: re-assess the diagnostic accuracy of MSOT	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	5-10 days
Secondary	Derivation Cohort: MSOT thresholds	Derive MSOT thresholds using histology as a reference: receiver operating characteristics (ROC) analysis to distinguish histologic active disease from remission.	9-10 months
Secondary	Derivation Cohort: MSOT performance, diagnostic accuracy measures	Diagnostic accuracy measures (area under curve (AUC), sensitivity, specificity) of MSOT to distinguish endoscopic active disease from remission.	9-10 months
Secondary	Derivation Cohort: MSOT performance, diagnostic accuracy	Diagnostic accuracy of MSOT to distinguish histologic active disease from remission	9-10 months
Secondary	Validation Cohort: MSOT performance, diagnostic accuracy measures	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	through study completion, an average of 1 year
Secondary	Validation Cohort: MSOT performance, diagnostic accuracy	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.	through study completion, an average of 1 year
Secondary	Both cohorts: diagnostic accuracy	Diagnostic accuracy of MSOT to distinguish clinical active disease from remission.	through study completion, an average of 1 year
Secondary	Both cohorts: performance of other non-invasive diagnostic modalities	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 con?dence intervals (DeLong) will be calculated. Score con?dence intervals (Wilson) will be calculated for proportions such as sensitivity, speci?city, and predictive values at the prede?ned thresholds.	through study completion, an average of 1 year
Secondary	Both cohorts: likelihood ratios and predictive values for active inflammation	Assess the likelihood ratios and predictive values for active inflammation after MSOT examination.	through study completion, an average of 1 year
Secondary	Both cohorts: performance of MSOT in combination with other modalities	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% con?dence interval (DeLong) both from the derivation cohort and from the pooled cohorts (derivation + validation) for increased precision. Cohen's ? 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).	through study completion, an average of 1 year
Secondary	Both cohorts: discriminate different grades of disease activity	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.	through study completion, an average of 1 year
Secondary	Both cohorts: interobserver variability	Explore variations in MSOT diagnostic accuracy between sites and operators (interobserver variability).	through study completion, an average of 1 year
Secondary	Both cohorts: patient preference	Evaluate patient preference for different tests using a patient survey	5-10 days
Secondary	Derivation cohort: MSOT thresholds using clinical scores as a reference	Derive MSOT thresholds using clinical scores as a reference: ROC analysis to distinguish clinical active disease from remission (only derivation cohort).	through study completion, an average of 1 year