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

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

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

Study Overview

• Status: Suspended
• Conditions: Inflammatory Bowel Diseases; Crohn Disease; Ulcerative Colitis
• Intervention / Treatment: Diagnostic test: Multispectral Optoacoustic Tomography (MSOT)

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.

• Study Type: Observational
• Enrollment (Anticipated): 540

Contacts and Locations

• Study Contact: Name: Claudia Jendrewski, MSc; Phone Number: +49 89 700744913; Email: claudia.jendrewski@ithera-medical.com
• Study Contact Backup: Name: Philipp Bell, Dr. rer.pol.; Phone Number: +49 89 700744911; Email: philipp.bell@ithera-medical.com

Study Locations

• Germany
  • Berlin, Germany, 12203
    • Charité- Universitätsmedizin Berlin, Campus Benjamin Franklin, Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Hindenburgdamm 30
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen Medizinische Klinik 1
  • Jena, Germany, 07747
    • Universitätsklinikum Jena
• Italy
  • Milan, Italy, 20132
    • I.R.C.C.S.San Raffaele, Gastroenterology and Gastrointestinal Endoscopy, Via Olgettina 60
  • Lazio
    • Roma, Lazio, Italy, 00133
      • Policlinico Tor Vergata
  • Lombardia
    • Rozzano, Lombardia, Italy, 20133
      • Centro per la Ricerca e la Cura delle Malattie Infiammatorie Croniche Intestinali IRCCS Humanitas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with confirmed diagnosis of CD or UC in whom endoscopy is indicated

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Derivation cohort; The derivation sub-cohort will be used to derive optimum reconstruction algorithm parameters of MSOT images. Primary objective of the derivation cohort is to derive Multispectral Optoacoustic Tomography (MSOT) thresholds maximizing receiver operating characteristic (ROC) to distinguish endoscopic remission from active disease. As secondary objective, performance of the Multispectral Optoacoustic Tomography (MSOT) device will be analyzed.	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.
Validation cohort; Objective of the validation cohort is to confirm the performance of Multispectral Optoacoustic Tomography (MSOT) using prescribed thresholds from the derivation cohort.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Derivation Cohort: MSOT performance, diagnostic accuracy	Diagnostic accuracy of MSOT to distinguish histologic active disease from remission	9-10 months
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
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
Both cohorts: diagnostic accuracy	Diagnostic accuracy of MSOT to distinguish clinical active disease from remission.	through study completion, an average of 1 year
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 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.	through study completion, an average of 1 year
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
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% 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).	through study completion, an average of 1 year
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
Both cohorts: interobserver variability	Explore variations in MSOT diagnostic accuracy between sites and operators (interobserver variability).	through study completion, an average of 1 year
Both cohorts: patient preference	Evaluate patient preference for different tests using a patient survey	5-10 days
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

Collaborators and Investigators

• Sponsor: iThera Medical GmbH
• Collaborators: European Commission

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2021
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: June 19, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (Actual): July 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 31, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: IBD; CD; UC
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: cMSOT-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No