Clinical trial NCT06482671: Primary Care dySpEpsia rikkuNshiTo
Official title: A Randomized Controlled Trial of Rikkunshito (TJ-43) in Functional Dyspepsia Patients Recruited From Primary Care
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Dyspepsia and Other Specified Disorders of Function of Stomach
Postprandial Distress Syndrome
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2024-07-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind intervention with Rikkunshito (herbal preparation) or Placebo
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
2. Use of highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner.
3. Male or female
4. 18 years old or older
5. Newly to be treated FD diagnosis
6. Capable to understand and comply with the study requirements

Exclusion Criteria:

* 1. Participant has a history of diabetes mellitus type 1, type 2 (including therapy), eosinophilic esophagitis, coeliac disease or inflammatory bowel disease, major abdominal surgery (except for appendectomy, cholecystectomy or splenectomy).

  2. Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol 3. Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial 4. If applicable: Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive 5. Patients with predominant symtoms of gastro-oesophageal reflux disease (GERD) or irritable bowel syndrome (IBS) 6. Patients with any active somatic or psychiatric condition that may explain dyspeptic symptoms (stable dose of single antidepressant allowed for psychiatric indication, no limitation for other indications) or severe depression using PHQ-7 (score of 20-27) 7. Patients already on PPI therapy20 or using a PPI in the last 2 weeks prior to enrolment 8. Patients with active malignancy (including therapy) 9. Known HIV, HBV, or HCV infection (including therapy) 10. Significant alcohol use (more than 10 units a week) 11. Known allergy to Rikkunshito or any of its ingredients 12. Patients with overweight (BMI\>26)

Primary outcomes:
measure: Percentage responders of Rikkunshito compared to placebo in FD
timeFrame: 8 weeks
Secondary outcomes:
measure: The effect of Rikkunshito versus placebo on duodenal mucosal integrity
timeFrame: 8 weeks
measure: The effect of Rikkunshito versus placebo on Immune activation
timeFrame: 8 weeks
measure: The effect of Rikkunshito versus placebo on duodenal microbiome
timeFrame: 8 weeks
measure: percentage minimal clinical response of rikkunshito
timeFrame: 8 weeks
measure: The effect of Rikkunshito versus placebo on PDS clinical symptoms
timeFrame: 8 weeks
measure: The effect of Rikkunshito versus placebo on gastrointestinal symptoms
timeFrame: 8 weeks
measure: The effect of Rikkunshito versus placebo on quality of life
timeFrame: 8 weeks
measure: The effect of Rikkunshito versus placebo on psychologic distress
timeFrame: 8 weeks
measure: The response to Rikkunshito in patients with normal versus those with delayed gastric emptying rate at baseline.
timeFrame: 8 weeks
measure: • The effect of Rikkunshito versus placebo at 8 weeks on gastric emptying rate in those with delayed emptying at baseline.
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: KU Leuven
state: Vlaams-Brabant
Study officials:
References: