Neuro-immune Interactions and PPI

Duodenal Neuro-immune Interactions and Effects of PPI in Functional Dyspepsia

Prospective interventional study on duodenal neuro-immune interactions in healthy volunteers and functional dyspepsia patients and the effects of PPI

Study Overview

• Status: Recruiting
• Conditions: Functional Dyspepsia
• Intervention / Treatment: Drug: Pantoprazole 40mg

Detailed Description

Duodenal low-grade inflammation is frequently reported in functional dyspepsia (FD), while also neuronal and structural changes in duodenal submucosal ganglia have been described in FD patients. Proton pump inhibitors (PPI) are the first-line therapy in FD patients and are recently shown to have anti-inflammatory properties in FD. However, the exact mechanism of their anti-inflammatory action is unknow and their effect on duodenal nerve signalling remain unclear.

In this prospective interventional study, FD patients will undergo study procedures before and after treatment with pantoprazole (Pantomed®) 40mg twice daily during 4 weeks, with a baseline comparison to healthy volunteers.

This study aims to provide an in-deep characterization of the inflammatory infiltrate in the duodenum of FD patients, and to unravel the effect of PPI-therapy on neuronal signalling, duodenal inflammation and neuro-immune interactions in FD.

Novel insights in the pathophysiology of FD, including the duodenal mucosal inflammation and impaired neuronal functioning, can provide a better understanding of this commonly and costly disorder. Moreover, these results will help to elucidate the anti-inflammatory effect of PPI, which will contribute to the discovery of predictive markers for therapeutic efficacy of PPI in FD.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Tim Vanuytsel, MD PhD; Phone Number: 32 16341973; Email: Tim.vanuytsel@kuleuven.be
• Study Contact Backup: Name: Lucas Wauters, MD; Phone Number: 32 16345238; Email: lucas.wauters@kuleuven.be

Study Locations

• Belgium
  • Belgie
    • Leuven, Belgie, Belgium, 3000
      • Recruiting
      • KU Leuven
      • Contact: Tim Vanuytsel, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients with FD diagnosis as per Rome IV criteria (EPS or PDS).
• Normal investigation including upper GI endoscopy.
• Patients have confirmed duodenal mucosal eosinophilia.
• Patients witnessed written informed consent.
• Patients aged between 18 and 64 years inclusive.
• Male or female (not pregnant or lactating and using contraception or postmenopausal).
• Subjects 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 (stable dose of single antidepressant allowed for psychiatric indication, no limitation for other indications).
• Patients presenting with predominant symptoms of irritable bowel syndrome (IBS) or of gastro-esophageal reflux disease (GERD).
• Patients with personal or family (first-degree relative) of diabetes mellitus, celiac disease, inflammatory bowel disease, psoriasis, lupus, scleroderma, rheumatic or other systemic auto-immune disease.
• Patients with eosinophilic esophagitis or eosinophilic gastroenteritis.
• Active H. pylori infection (or <6 months after eradication).
• Allergy or atopy, including therapy.
• Organic gastro-intestinal disease or history of gastrointestinal surgery other than appendectomy or splenectomy.
• Known impaired liver or kidney dysfunction, or coagulation disorders.
• Known HIV, HBV or HCV infection, including therapy.
• Active coronary or peripheral artery disease.
• Use of anti-inflammatory drugs or anti-allergy drugs <2 weeks before sampling.
• Use of immunosuppressants, antibiotics or acid-suppressive drugs <3 months before sampling.
• Use of prokinetics <2 weeks before sampling (unless if ≤3/week).
• Significant alcohol use (>10 units/week).
• Any use of alcohol or smoking <2 days before sampling.
• Active malignancy, including therapy.
• Females who are pregnant or lactating.
• Patients not capable to understand or be compliant with the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Functional dyspepsia patients before and after PPI; Pantoprazole 40mg twice daily in functional dyspepsia patients for 4 weeks	Drug: Pantoprazole 40mg; Pantoprazole 40mg twice daily; Other Names: Pantomed
No Intervention: Healthy controls before PPI; Baseline investigations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effect of PPI on calcium transient amplitudes after electrical stimulation of submucosal neurons in FD	Calcium transient amplitudes after electrical stimulation of interconnecting fiber bundles before and after PPI	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effect of PPI on duodenal mucosal inflammation (assessed by flow cytometry on lamina propria leukocytes) in FD	Duodenal mucosal inflammation as assessed by flow cytometric quantification of immune cell populations in isolated lamina propria leukocytes before and after PPI	4 weeks
The effect of PPI on systemic inflammation (assessed by inflammatory cytokine levels in plasma) in FD	Systemic inflammation quantified by inflammatory cytokine levels in plasma before and after PPI	4 weeks
The effect of PPI on symptoms (Patient Assessment of Upper Gastrointestinal Disorders - Symptom severity index [PAGI-SYM]) in FD	PAGI-SYM symptom scores (ranging from 0 [no symptoms] to 5 [very severe symptoms]) before and after PPI	4 weeks
The effect of PPI on quality of life (Patient Assessment of Upper Gastrointestinal Disorders - Quality of Life [PAGI-QOL]) in FD	PAGI-QOL scores (ranging from 0 [lowest quality of life] to 5 [highest quality of life]) before and after PPI	4 weeks
The effect of PPI on salivary cortisol in FD	salivary cortisol before and after PPI	4 weeks
The effect of PPI on stool microbiota (quantitative microbiota profiling [QMP]) in FD	Stool microbiota assessed by quantitative microbiota profiling (QMP) before and after PPI	4 weeks
The effect of PPI on urine metabolites in FD	urine metabolites before and after PPI	4 weeks

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Tim Vanuytsel, MD PhD, Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2021
• Primary Completion (Estimated): January 31, 2024
• Study Completion (Estimated): January 31, 2024

Study Registration Dates

• First Submitted: December 17, 2020
• First Submitted That Met QC Criteria: January 13, 2021
• First Posted (Actual): January 19, 2021

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: imaging; inflammation
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Dyspepsia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Pantoprazole
• Other Study ID Numbers: S64807/64847

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No