Evaluation of Budesonide for Duodenal Eosinophilia in Functional Dyspepsia: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to evaluate the effect of **budesonide** on duodenal eosinophilia in patients with **Functional Dyspepsia**. This is clinically relevant as duodenal eosinophilia is implicated in the pathophysiology of functional dyspepsia, and addressing it may lead to improved management of the condition.

Secondary objectives include assessing the effect of budesonide on various aspects of functional dyspepsia:

• Gastric sensorimotor function
• Symptom outcome
• Quality of life in patients
• State of anxiety, depression, and somatization
• Mucosal barrier function
• The mucosal microbiome

The clinical trial focuses on evaluating the effect of Budesonide on duodenal eosinophilia in patients diagnosed with **Functional Dyspepsia**. The study population comprises both male and female participants aged between 18 and 70 years, inclusive. Participants are selected based on the presence of meal-related symptoms, specifically postprandial distress syndrome, as defined by the Rome IV criteria. The trial includes a vulnerable population, although specific details regarding the total number of participants have not been provided by the sponsor. The selection criteria ensure a diverse representation of adults experiencing functional dyspepsia, without specific emphasis on lifestyle factors such as diet or physical activity.

The clinical trial is designed to evaluate the effect of **budesonide** on duodenal eosinophilia in patients with **functional dyspepsia**. This study is a randomized, double-blind, controlled trial, involving the administration of Jorveza 1 mg orodispersible tablets, with a placebo group receiving Mannitol, 1mg, for oral use. The trial is set to commence on May 1, 2024, and is expected to conclude by May 31, 2026. The total duration of the trial for each participant is 12 weeks, with the primary endpoint being the assessment of duodenal eosinophils before and after 8 weeks of treatment. Secondary endpoints include evaluations of gastrointestinal symptoms, quality of life, psychological states, mucosal permeability, gastric motility, and the mucosa-associated microbiome, all assessed before and after the 8-week treatment period.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18-70 years), gender (male or female), and the presence of meal-related symptoms as per the Rome IV criteria. Following the screening, participants will be randomized to receive either the active treatment or placebo. Follow-up visits will occur at regular intervals to monitor treatment effects and ensure participant safety. The end-of-study visit will involve comprehensive assessments to evaluate the primary and secondary endpoints. Participant involvement is expected to last for the full 12-week treatment period unless early termination is warranted due to adverse events, non-compliance, or withdrawal of consent. The trial is not classified as low intervention, and it is conducted under the therapeutic use category for **budesonide** in **functional dyspepsia** patients.

The clinical trial involves the administration of **Jorveza 1 mg orodispersible tablets**, which contain the active substance **budesonide**. Budesonide is classified under the ATC code A07EA06. The pharmaceutical form of the medication is an orodispersible tablet, designed to dissolve in the mouth for oral administration. The maximum daily dose of budesonide is 9 mg, with a total maximum dose of 630 mg over the treatment period. The treatment duration is set for a maximum of 12 weeks. The medication is manufactured by DR. FALK PHARMA G.M.B.H. and is not a paediatric formulation. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

In addition to the experimental treatment, the study includes a **placebo** group receiving **Mannitol, 1 mg, Oral use**. Mannitol serves as the placebo comparator in this trial. The pharmaceutical form and specific details regarding the administration of Mannitol are not provided. The placebo is intended to mimic the administration of the active treatment without providing any therapeutic effect, allowing for the assessment of budesonide's efficacy in treating low-grade duodenal inflammation in functional dyspepsia. Participant compliance with the placebo administration will also be monitored to maintain the integrity of the trial results.

Efficacy in the clinical trial evaluating **Budesonide** for the treatment of low-grade duodenal inflammation in functional dyspepsia will be assessed using both primary and secondary endpoints. The primary endpoint involves measuring the number of duodenal eosinophils before treatment and after 8 weeks of treatment. This will provide a direct assessment of the effect of Budesonide on duodenal eosinophilia.

Secondary endpoints include a comprehensive evaluation of various parameters before and after 8 weeks of treatment. These parameters are: gastro-intestinal symptoms assessed using the Leuven Postprandial Distress Scale (LPDS), quality of life, and psychological states such as anxiety, depression, and somatization. Additionally, mucosal permeability will be evaluated by examining gene and protein expression of major tight-junction related molecules and cytokines. Gastric motility will be assessed by measuring gastric emptying time, gastric sensitivity to distension, and the gastric accommodation reflex. The mucosa-associated microbiome will also be analyzed.

These efficacy parameters will be collected and analyzed at specified timepoints, specifically before treatment initiation and after 8 weeks of treatment. The use of validated scales and laboratory tests will ensure the reliability and accuracy of the data collected. The trial aims to provide a comprehensive understanding of the therapeutic effects of Budesonide in patients with functional dyspepsia.