The EUPHORIA Clinical Study:

Enhancing Ultrasound & Photoacoustic for Recognition of Intestinal Abnormalities

What is the EUPHORIA clinical study (ClinicalTrials.gov identifier NCT04456400)?

Inflammatory bowel disease (IBD) is a chronic condition that poses a significant burden on patients and health care systems. People with IBD suffer from a relapsing course of intestinal inflammation, and to date, there is no satisfying non-invasive diagnostic modality for monitoring disease activity.

The goal of the EUPHORIA clinical study is to assess the ability of a new medical device – the MSOT Acuity Echo system – to measure inflammatory disease activity in people with Crohn’s disease (CD) or ulcerative colitis (UC). To investigate the value of this technology, the diagnostic performance of the MSOT Acuity Echo system will be compared to other commonly used diagnostic assessments, such as endoscopy, ultrasound, blood values, and MRI.

The MSOT Acuity Echo system (Figure 1) is a non-invasive device that uses a new imaging modality called Multispectral Optoacoustic Tomography (MSOT). This technique combines laser illumination of tissue with ultrasound detection: molecules in soft tissues (such as the colon wall) absorb ultra-short light pulses from laser illumination through the handheld probe, leading to momentary expansion and contraction on a molecular scale. This results in the emission of ultrasound waves, which are detected by the probe and formed into an image with anatomical, functional, and molecular information of the examined area of the body. The process of the MSOT assessment is similar to a standard abdominal ultrasonography assessment with a handheld detector (Figure 2).

Figure 1: The MSOT Acuity Echo system used in EUPHORIA

Figure 2: Principle of abdominal MSOT imaging. Laser illumination interacts with naturally-occurring molecules in soft tissue to generate ultrasound waves, which are then detected by the handheld transducer.

A previous pilot study using the same fundamental technology in the MSOT Acuity Echo system demonstrated that the system can non-invasively distinguish active disease from remission. While these early findings were encouraging, the study only involved a small cohort of 40 subjects. The EUPHORIA study intends to confirm these findings with a large-scale, multi-national clinical study in both CD and UC.

For this study, a total of approximately 540 participants are expected to be enrolled – about half of which will be patients with CD and half with UC. The study will be divided into 2 phases; the first phase will determine the optimal device parameters to distinguish active disease from remission. The second phase will utilize the parameters from the first phase and confirm the accuracy of the device.

What does participation involve?

During the study, participants are first screened and then examined with both MSOT as well as standard-of-care IBD diagnostic assessments. Examinations and assessments will be performed by EUPHORIA physicians. A flow chart of the steps of the EUPHORIA clinical study illustrates the participant experience (Figure 3). Individual steps are described in detail further below.

Figure 3: EUPHORIA clinical study flowchart.

Screening, consent, and eligibility

First, patients are screened for candidacy to participate in EUPHORIA based on known conditions. Criteria include a confirmed diagnosis of IBD (either UC or CD) and a timely medical need for endoscopy.

Following a successful screening to identify likely prospective participants, candidates are informed in detail by a physician of what participation entails and what participants can expect. Interested candidates provide voluntary informed consent – a necessary prerequisite before any assessments and examinations may proceed.

Once informed consent is given, the physician performs a check of eligibility for participation in EUPHORIA. This includes documenting patient demographics, such as age and gender. Additional assessments may be necessary to confirm eligibility. All assessments performed during the screening are standard of care.

 

MSOT assessment

Once participant consent is given and eligibility for the study is confirmed, the MSOT assessment can be performed. In general, the MSOT assessment is similar to a standard abdominal ultrasonography assessment with a handheld detector, with the exception that participants must wear protective laser safety glasses.

Participants lay on a patient bed for the examination, wearing laser safety glasses provided by the physician. In some cases, the region of interest (belly) may need to be shaved if hair is present, as hair interferes with MSOT data acquisition. To ensure good image quality, ultrasound coupling gel is applied on the probe and belly prior to scanning. The physician scans the belly several times using the probe to obtain several MSOT images of the bowel wall (see Figure 4).

Figure 4: Assessment of the abdominal region with MSOT imaging.

Different regions of the colon are scanned. The end of the large intestine (sigmoid colon) is scanned for all participants. The end of the small intestine (terminal ileum) is also scanned in patients with CD. In cases where a resection surgery of this region has previously been performed, the newly formed end of the small intestine (neoterminal ileum) is also scanned.

Each region is scanned three times with two different MSOT settings. In total, the MSOT assessment lasts approximately 15 minutes.

 

Other assessments

Apart from the MSOT assessment, the diagnostic assessments that are standard of care for patients with IBD are also performed. These assessments include abdominal ultrasonography, clinical disease activity assessment, blood and stool sample test, histology, and endoscopy.

All of these assessments are performed either on the same day of the MSOT assessment or during additional visit(s) within 5 days after the MSOT assessment.

Whether all assessments are performed within one day or multiple days is determined separately and individually for each participant and in consultation with the physician.

For CD patients in the second phase of the study, a standard MRI is conducted within 10 days of the MSOT assessment. This may require the participant to return to the hospital for an additional visit.

After completion of all diagnostic assessments, each participant is asked to complete a questionnaire to rate their experience with each assessment performed on a 5-point scale and to give feedback on their impression of the MSOT scan.

The patient is only scanned with the MSOT Acuity Echo system if they voluntarily decide to participate in the study. The MSOT scan is conducted in addition to the usual standard of care of the hospital, and no medical decisions will be based on the MSOT scan results regardless of findings.

 

Who can take part in this clinical study?

The study is designed for people with a confirmed diagnosis of CD or UC in cases where endoscopy is required as a useful assessment of disease status.

 

Criteria

Inclusion Criteria:

  • Age ≥ 18 years
  • Written informed consent
  • Medical need for endoscopy according to the assessing institute’s routine care
  • Established diagnosis of UC or CD for at least three months prior to enrolment

Exclusion Criteria:

 

If a participant is enrolled, what is expected of them?

It is important that participating patients follow the study instructions both to carry out the study properly and for their own safety. The study instructions require that each participant:

  • Provides accurate information relating to their state of health, the medication they are taking, or the symptoms they are experiencing.
  • Keeps appointments for visits.

It is important to contact the EUPHORIA physician if the participant:

  • Is admitted to or receives treatment at a hospital.
  • Suddenly develops any health problems.
  • No longer wishes to participate in the study.
  • Changes their contact details.

With the exception of emergency situations, new medications or medical devices may only be used after consultation with the participant’s EUPHORIA physician. If the participant is being treated by other physicians, they must inform them of their participation in the EUPHORIA clinical study. The participant’s EUPHORIA physician must also be informed of every medical treatment that they receive from another physician during their participation in the clinical study.

 

Who initiated this study?

This study was designed by iThera Medical, the manufacturer of the MSOT Acuity Echo system, and Prof. Maximilian Waldner, the Coordinating Investigator of the EUPHORIA clinical study. The study is carried out by physicians at various hospitals. The costs of this study are paid for by iThera Medical with support from the European Union’s Horizon 2020 research and innovation programme through the EUPHORIA project (under grant agreement No. 830965).

The EUPHORIA study will commence at each site (below) once ethical and regulatory approval for the study are obtained from the relevant Competent Authorities.

Additional information about this study can be found in a list of registered clinical studies at  https://clinicaltrials.gov/ct2/show/study/NCT04456400. Upon completion of the EUPHORIA clinical study, this website will display a summary of the results of the study.

 

Who can I contact to get involved?

Site 01:

Prof. Dr. med. Maximilian Waldner

Universitätsklinikum Erlangen

Medizinische Klinik 1

Ulmenweg 18, 91054 Erlangen

Germany

 

Study Coordinator:

Dr. med. Daniel Klett

E-Mail:

Phone: + 49 9131 85-35000/-35204

 

 

Site 02:

Prof. Dr. Andreas Stallmach

Universitätsklinikum Jena

Klinik für Innere Medizin IV

Am Klinikum 1, 07747 Jena

Germany

 

Study Coordinator:

Dr. rer. nat. Anja Schauer

E-Mail:

Phone: +49 3641-9324582

 

 

Site 03:

Mariangela Allocca, MD, PhD

Centro per la Ricerca e la Cura delle Malattie Infiammatorie Croniche Intestinali

IRCCS Humanitas

via Manzoni 56, 20089 Rozzano (MI)

Italy

 

Study Coordinator:

Daniela Gilardi, PharmD

E-Mail:

Phone +39 02 8224 7303

 

 

Site 04:

Prof. Giovanni Monteleone

Policlinico Tor Vergata

UOC di Gastroenterologia

Viale Oxford n. 81 – Roma (00133)

Italy

 

Study Coordinator:

Dr. Elvira Scalera

E-Mail:

 

Note: The above summary is general information about the study only and should not be relied upon in any individual case. Before deciding to participate in the study, each interested candidate will be given detailed information about the study so that they can make a voluntary informed decision whether to participate or not. Only candidates who are eligible to participate in the study and provide informed consent can join. Participation may be possible at the sites only up to a certain maximum number of participants.