Primary Care dySpEpsia rikkuNshiTo
NCT Number: NCT06482671
Acronym: PRESENT
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Dyspepsia and Other Specified Disorders of Function of Stomach|Postprandial Distress Syndrome
Interventions: DRUG: Rikkunshi-to|OTHER: Placebo
Sponsor: Universitaire Ziekenhuizen KU Leuven
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 100
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-10-01
Completion Date: 2026-10-01
Locations: KU Leuven, Leuven, Vlaams-Brabant, 3000, Belgium

Summary:
Dyspepsia refers to chronic or recurrent upper gastrointestinal (GI) symptoms originating from the gastroduodenal region with a significant impact on patients' lives. Functional dyspepsia comprises the diagnostic categories of epigastric pain syndrome (EPS) with epigastric pain or burning and postprandial distress syndrome (PDS) with meal-related fullness or early satiation, which are unexplained after routine investigation including upper GI endoscopy 2. Despite the common occurrence of FD in up to 15% of the general population, the underlying pathophysiology remains unclear and no treatments of proven efficacy are available in Europe for this condition.

Our group has demonstrated increased duodenal mucosal permeability and low-grade inflammation in FD patients, correlating with meal-related symptoms. The causes of the barrier defect and immune activation are unknown but candidates include psychological stress, luminal food components, (bile) acid and microbiota. The symptoms most closely associated with increased eosinophil counts in the duodenum are early satiation and postprandial fullness, which are typical PDS symptoms, and which are also associated with impaired gastric accommodation to meal ingestion and delayed gastric emptying.

Previously the efficacy of the Kampo medicine Rikkunshito (TJ-43) has been shown in FD. The exact mode of action remains to be determined. Previous studies have provided mechanistic evidence that rikkunshito is able to improve gastric accommodation, improve food intake and enhance circulating levels of the orexigenic gut peptide ghrelin.

The aim of this study is to evaluate the efficacy of Rikkunshito in comparison to placebo in PDS patients recruited from primary care in Belgium, and to evaluate whether this is associated with changes in duodenal mucosal low-grade inflammation.

Primary Outcome Measures: Percentage responders of Rikkunshito compared to placebo in FD, Number of patients clinically relevant difference of 0.7 for the PDS symptoms (average of 3 questions of LPDS diary) by comparing pretreatment baseline scores with the average score during the last 2 weeks on treatment (responder definition). And compared Rikkunshito versus placebo., 8 weeks
Secondary Outcome Measures: The effect of Rikkunshito versus placebo on duodenal mucosal integrity, mucosal permeability and electrical resistance measured by Ussing-Chambers in duodenal biopsies, 8 weeks|The effect of Rikkunshito versus placebo on Immune activation, Assessment of immune cell counts (mast cells and eosinophils) in duodenal biopsies, 8 weeks|The effect of Rikkunshito versus placebo on duodenal microbiome, Assessment of DNA of bacteria at the level of duodenal mucosa biopsies, 8 weeks|percentage minimal clinical response of rikkunshito, Number of patients clinically relevant difference of 0.5 for the PDS symptoms (average of 3 questions of LPDS diary) by comparing pretreatment baseline scores with the average score during the last 2 weeks on treatment (minimal clinical relevant reseponse definition). And compared Rikkunshito versus placebo., 8 weeks|The effect of Rikkunshito versus placebo on PDS clinical symptoms, assessed with the LPDS daily diary, 8 weeks|The effect of Rikkunshito versus placebo on gastrointestinal symptoms, assessed by PAGI-SYM questionnaire, 8 weeks|The effect of Rikkunshito versus placebo on quality of life, Assessed with the PAGI-Qol questionnaire, 8 weeks|The effect of Rikkunshito versus placebo on psychologic distress, Assessed by the PHQ questionnaire, 8 weeks|The response to Rikkunshito in patients with normal versus those with delayed gastric emptying rate at baseline., assessed with the C13 gastric emptying breath test, 8 weeks|• The effect of Rikkunshito versus placebo at 8 weeks on gastric emptying rate in those with delayed emptying at baseline., assessed with the C13 gastric emptying breath test, 8 weeks