Budesonide as a Treatment for Functional Dyspepsia

Official title

Budesonide as a Treatment for Low-grade Duodenal Inflammation in Functional Dyspepsia

Overview

This clinical study is being conducted to evaluate the investigational drug, Budesonide, for the treatment of functional dyspepsia. The goal of this study is to learn more about the effect of Budesonide on patients with functional dyspepsia. Budesonide is a well-known and commonly used drug, and is part of the recommended therapy for patients with inflammatory bowel diseases (Crohn's disease or ulcerative colitis). It is also used as inhalation therapy for respiratory conditions such as asthma and COPD. However, the effect of Budesonide in patients with functional dyspepsia is still unknown. In patients with functional dyspepsia, an increased presence of inflammatory cells has been observed in the duodenum. Budesonide may reduce inflammatory responses. Therefore, with this study, the investigators aim to investigate primarily: 1. Whether Budesonide has an effect on the inflammatory cells observed in functional dyspepsia. 2. Whether the symptoms of patients with functional dyspepsia improve during and after taking Budesonide. 3. Whether inflammatory cells could be the cause of symptoms in functional dyspepsia.

Interventions

• Drug budesonide
  During an 8-week treatment period, patients will receive 9 mg of Budesonide daily, administered orally in enteric-coated capsules. Following this period, participants will undergo a gradual dose reduction to minimize the risk of adrenal insufficiency: 6 mg daily for 2 weeks, followed by 3 mg daily for another 2 weeks before discontinuing treatment.
• Drug Mannitol
  During an 8-week treatment period, patients will receive 9 mg of Mannitol daily, administered orally in enteric-coated capsules as placebo control. Following this period, participants will undergo a gradual dose reduction as is the case in the experimental group: 6 mg daily for 2 weeks, followed by 3 mg daily for another 2 weeks before discontinuing treatment.

Primary outcome measures

• Effect of Budesonide on the reduction of the number of eosinophils on duodenal biopsies in patients with functional dyspepsia [Time frame: before treatment and 8 weeks after start of treatment (9 mg)]

Secondary outcome measures (9)

• The effect of budesonide in functional dyspepsia on gastric emptying time. [Time frame: before treatment and 8 weeks after start of treatment (9 mg)]
• The effect of budesonide in functional dyspepsia on symptom outcome using the Leuven Postprandial Distress Scale (range 0-4; 0 = no symptoms, 4 = very severe symptoms) [Time frame: Daily for 2 weeks before start of treatment. Daily during the 8 weeks of treatment (at 9 mg). Daily during the 4 weeks of tapering the treatment]
• The effect of budesonide in functional dyspepsia on Quality of life of patients [Time frame: At baseline, 8 weeks after start of treatment (9mg), 2 weeks after start of tapering (which is at 10 weeks), at the end of tapering (at 12 weeks), at 16 weeks (4 weeks after treatment discontinuation)]
• The effect of budesonide in functional dyspepsia on Quality of life of patients [Time frame: At baseline, 8 weeks after start of treatment (9mg), 2 weeks after start of tapering (which is at 10 weeks), at the end of tapering (at 12 weeks), at 16 weeks (4 weeks after treatment discontinuation)]
• The effect of budesonide in functional dyspepsia on state of anxiety [Time frame: At baseline, 8 weeks after start of treatment (9mg), 2 weeks after start of tapering (which is at 10 weeks), at the end of tapering (at 12 weeks), at 16 weeks (4 weeks after treatment discontinuation)]
• The effect of budesonide in functional dyspepsia on state of depression [Time frame: At baseline, 8 weeks after start of treatment (9mg), 2 weeks after start of tapering (which is at 10 weeks), at the end of tapering (at 12 weeks), at 16 weeks (4 weeks after treatment discontinuation)]
• The effect of budesonide in functional dyspepsia on state of somatization [Time frame: At baseline, 8 weeks after start of treatment (9mg), 2 weeks after start of tapering (which is at 10 weeks), at the end of tapering (at 12 weeks), at 16 weeks (4 weeks after treatment discontinuation)]
• The effect of budesonide in functional dyspepsia on barrier function by measuring mRNA levels of tight-junction related molecules [Time frame: before treatment and 8 weeks after start of treatment (9 mg)]
• The effect of budesonide in functional dyspepsia on barrier function by measuring mRNA levels of pro-inflammatory cytokines [Time frame: before treatment and 8 weeks after start of treatment (9 mg)]

Eligibility criteria

Inclusion criteria

• Patients with Functional dyspepsia (subtype postprandial distress syndrome) as per Rome IV diagnostic criteria

• Symptom characteristics of dyspepsia (upper gastrointestinal symptoms occurring in the last 3 months and meal related)
• Negative endoscopy (maximum 12 months old)
• Patients must provide witnessed written informed consent prior to any study procedures being performed
• Patients aged between 18 and 70 years inclusive
• Male or female patients
• Women of child-bearing potential agree to apply a highly effective method of birth control during the entire duration of the trial. Highly effective birth control is defined as those which result in a low failure rate (i.e., less than 1% per year) when used constantly and correctly such as implants, injectables, combined oral contraceptive method, or some intrauterine devices (IUDs), sexual abstinence, or vasectomized partner. Women of non-childbearing potential may be included if surgically sterile (tubal ligation or hysterectomy) or postmenopausal with at least 2 year without spontaneous menses
• Subjects who are capable to understand the study and the questionnaires, and to comply with the study requirements

Exclusion criteria

• Patients with any condition which, in the opinion of the investigator, makes the patient unsuitable for entry into the study
• Patients with any major psychiatric disorders (including those with a major psychosomatic element to their gastrointestinal disease), depression, alcohol or substance abuse in the last 2 years
• Patients presenting with predominant symptoms of irritable bowel syndrome (IBS) or of gastro-esophageal reflux disease (GERD)
• Presence of diabetes mellitus, celiac disease (diagnosed with presence of anti-tissue transglutaminase antibodies and anti-gliadin antibodies or via duodenal biopsies), lupus, scleroderma or other systemic auto-immune disease
• Patients with eosinophilic esophagitis or eosinophilic gastroenteritis
• Active H. Pylori infection (or < 6 months after eradication)
• Organic gastro-intestinal disease of history of gastrointestinal surgery other than appendectomy
• Known impaired liver dysfunction
• Drugs altering gastric emptying, anti-inflammatory drugs, acid suppressive drugs or some drugs altering the CYP3A4 metabolism
• Major change in diet last 3 months
• Females who are pregnant or lactating
• Patients not capable to understand or be compliant with the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Belgium · 1 center

• UZ Leuven — Leuven

Identifiers

NCT: NCT06841406 · S64291

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗