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Neuro-immune Interactions and PPI

Primary Purpose

Functional Dyspepsia

Status

Recruiting

Phase

Phase 4

Locations

Belgium

Study Type

Interventional

Intervention

Pantoprazole 40mg

About this trial

This is an interventional treatment trial for Functional Dyspepsia focused on measuring inflammation, imaging

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

KU LeuvenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Functional dyspepsia patients before and after PPI

Healthy controls before PPI

Arm Description

Pantoprazole 40mg twice daily in functional dyspepsia patients for 4 weeks

Baseline investigations

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

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

The effect of PPI on salivary cortisol in FD

salivary cortisol before and after PPI

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

The effect of PPI on urine metabolites in FD

urine metabolites before and after PPI

Full Information

NCT ID

NCT04713969

First Posted

December 17, 2020

Last Updated

March 30, 2023

Sponsor

Universitaire Ziekenhuizen KU Leuven

1. Study Identification

Unique Protocol Identification Number

NCT04713969

Brief Title

Neuro-immune Interactions and PPI

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Recruiting

Study Start Date

March 31, 2021 (Actual)

Primary Completion Date

January 31, 2024 (Anticipated)

Study Completion Date

January 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Universitaire Ziekenhuizen KU Leuven

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Functional Dyspepsia

Keywords

inflammation, imaging

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

Intervention with PPI (Pantoprazole 40mg twice daily) in 30 FD patients. Baseline procedures in 30 healthy controls.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Functional dyspepsia patients before and after PPI

Arm Type

Experimental

Arm Description

Pantoprazole 40mg twice daily in functional dyspepsia patients for 4 weeks

Arm Title

Healthy controls before PPI

Arm Type

No Intervention

Arm Description

Baseline investigations

Intervention Type

Drug

Intervention Name(s)

Pantoprazole 40mg

Other Intervention Name(s)

Pantomed

Intervention Description

Pantoprazole 40mg twice daily

Primary Outcome Measure Information:

Title

The effect of PPI on calcium transient amplitudes after electrical stimulation of submucosal neurons in FD

Description

Calcium transient amplitudes after electrical stimulation of interconnecting fiber bundles before and after PPI

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

The effect of PPI on duodenal mucosal inflammation (assessed by flow cytometry on lamina propria leukocytes) in FD

Description

Duodenal mucosal inflammation as assessed by flow cytometric quantification of immune cell populations in isolated lamina propria leukocytes before and after PPI

Time Frame

4 weeks

Title

The effect of PPI on systemic inflammation (assessed by inflammatory cytokine levels in plasma) in FD

Description

Systemic inflammation quantified by inflammatory cytokine levels in plasma before and after PPI

Time Frame

4 weeks

Title

The effect of PPI on symptoms (Patient Assessment of Upper Gastrointestinal Disorders - Symptom severity index [PAGI-SYM]) in FD

Description

PAGI-SYM symptom scores (ranging from 0 [no symptoms] to 5 [very severe symptoms]) before and after PPI

Time Frame

4 weeks

Title

The effect of PPI on quality of life (Patient Assessment of Upper Gastrointestinal Disorders - Quality of Life [PAGI-QOL]) in FD

Description

PAGI-QOL scores (ranging from 0 [lowest quality of life] to 5 [highest quality of life]) before and after PPI

Time Frame

4 weeks

Title

The effect of PPI on salivary cortisol in FD

Description

salivary cortisol before and after PPI

Time Frame

4 weeks

Title

The effect of PPI on stool microbiota (quantitative microbiota profiling [QMP]) in FD

Description

Stool microbiota assessed by quantitative microbiota profiling (QMP) before and after PPI

Time Frame

4 weeks

Title

The effect of PPI on urine metabolites in FD

Description

urine metabolites before and after PPI

Time Frame

4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tim Vanuytsel, MD PhD

Phone

16341973

Ext

Tim.vanuytsel@kuleuven.be

First Name & Middle Initial & Last Name or Official Title & Degree

Lucas Wauters, MD

Phone

16345238

Ext

lucas.wauters@kuleuven.be

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tim Vanuytsel, MD PhD

Organizational Affiliation

Universitaire Ziekenhuizen KU Leuven

Official's Role

Principal Investigator

Facility Information:

Facility Name

KU Leuven

City

Leuven

State/Province

Belgie

ZIP/Postal Code

3000

Country

Belgium

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Tim Vanuytsel, MD PhD

12. IPD Sharing Statement

Plan to Share IPD

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Neuro-immune Interactions and PPI

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