Evaluation of Transabdominal Ultrasound with Perflubutane and Laxative Combination for Small Bowel Assessment in Crohn's Disease

The primary objective of this study is to develop a method for investigating the small bowel in **Crohn's disease** using transabdominal ultrasound and microbubbles as luminal contrast. This objective is clinically relevant as it aims to enhance the diagnostic capabilities for Crohn's disease, potentially leading to improved patient management and outcomes.

Secondary objectives include:

• Investigate adverse events and severe adverse events.
• Investigate tolerability of the procedure.
• Investigate if luminal contrast can be used to detect stenosis and ulcers in the terminal ileum, including differentiation of ulcer sizes.
• Investigate if luminal contrast affects the measurement of wall thickness in the terminal ileum.
• Investigate if luminal contrast can be used to detect motility in the small intestine and postsurgical relapse in the neoterminal ileum.
• Investigate intestinal motility in patients with ulcers or stenosis in the terminal ileum and how it is affected by the degree of inflammation.
• Investigate differences in motility findings between patients with Crohn’s disease and healthy volunteers.

The clinical trial involves participants diagnosed with **Crohn's disease**, specifically affecting the terminal ileum, as well as healthy volunteers. The study population includes both male and female subjects aged over 18 years. Participants are required to be capable of providing informed consent, which includes adherence to the study's requirements and restrictions. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. The selection criteria include individuals with Crohn's disease who are undergoing ileocolonoscopy and healthy volunteers without known gastrointestinal illnesses. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate a novel method for investigating the small bowel in **Crohn's disease** using transabdominal ultrasound and microbubbles as luminal contrast. This is a Phase 4, randomized, double-blind, controlled study aimed at determining the efficacy of ultrasound with oral contrast in improving diagnostic applications for patients with Crohn's disease. The trial is expected to commence on January 1, 2025, and conclude by December 31, 2028. Participants will be involved in the study for a maximum treatment period of one day, with the primary endpoint being the number of patients achieving homogenous contrast filling of the terminal ileum within one hour of ingestion.

The study will include an initial screening visit to assess eligibility based on criteria such as age, diagnosis of Crohn's disease in the terminal ileum, and the ability to provide informed consent. Following the screening, eligible participants will undergo the investigational procedure, which involves the administration of oral contrast and subsequent ultrasound examination. Follow-up visits will be scheduled to monitor for adverse events and assess the primary and secondary endpoints, including the detection of stenosis and ulcers, interobserver variability, and motility findings.

The end-of-study visit will involve a comprehensive evaluation of the participant's condition and the collection of final data points. Participants may be withdrawn from the study if they experience severe adverse events, are unable to comply with study procedures, or withdraw consent. The trial will also include healthy volunteers as a control group to compare motility findings. The study aims to provide valuable insights into the use of ultrasound with oral contrast in the diagnosis and management of Crohn's disease, potentially leading to improved patient outcomes.

The clinical trial involves the use of two experimental medications. The first medication is **Laxabon**, which is formulated as a powder for oral solution, packaged in sachets containing 68.5 g each. The active substances in Laxabon include **sodium hydrogen carbonate**, **potassium chloride**, **sodium chloride**, **sodium sulfate anhydrous**, and **macrogol 3350**. This medication is administered orally, with a maximum daily dose of 500 ml, and the treatment period is limited to one day. The primary role of Laxabon in the trial is as a laxative, facilitating bowel preparation for diagnostic procedures.

The second experimental medication is **Sonazoid**, which is a dispersion for injection. The active substance in Sonazoid is **perflubutane**, a chemical compound used as a contrast agent. The pharmaceutical form is a powder and liquid for dispersion, intended for injection. The maximum daily dose is 1 ml, and similar to Laxabon, the treatment period is restricted to one day. Sonazoid is utilized in the trial to enhance sonographic imaging, providing contrast for the detection of Crohn's disease through transabdominal ultrasound.

Both medications are administered according to the specified dosing schedules, and participant compliance is monitored throughout the trial to ensure adherence to the protocol. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. The focus is on evaluating the efficacy of these experimental medications in improving diagnostic accuracy for Crohn's disease.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints designed to evaluate the effectiveness of a novel sonographic diagnostic method for **Crohn's disease**. The primary endpoint focuses on the number of patients achieving homogenous contrast filling of the entire lumen of the terminal ileum within one hour of ingestion, with a clear separation between the lumen and intestinal wall, as visually assessed by the examiner. This endpoint is crucial for determining the diagnostic clarity provided by the contrast method.

Secondary endpoints include a variety of measures to further assess the diagnostic capabilities and patient outcomes. These include the number of patients experiencing adverse events, willingness to undergo the procedure again, and detection of stenosis and ulcers in the terminal ileum with and without contrast. Additionally, the study will evaluate interobserver variability for wall thickness, the presence of visible intestinal contractions, and correlations between ulcer size, bowel wall thickness, and frequency of contractions. The study will also compare motility findings between Crohn's patients and healthy volunteers, and assess disease activity in the neoterminal ileum with and without contrast.