Mast Cells in Acid-induced Intestinal Permeability

NCT ID: NCT02664051

Last Updated: 2024-07-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2021-06-29

Brief Summary

This is a randomized, double-blind, cross-over study in healthy volunteers. In the first part, the duodenum of the participants will be perfused with acid or saline, during which intragastric pressure will be monitored to assess activation of the duodenogastric reflex. After perfusion, duodenal biopsies will be collected to evaluate mucosal integrity. In the second part, healthy volunteers are treated with the mast cell stabilizer disodium cromoglycate or with a placebo during 14 days. Subsequently, the duodenum will be perfused with acid and intragastric pressure and mucosal integrity will be evaluated.

Detailed Description

Despite intensive research, the pathophysiology of functional dyspepsia remains unknown. The investigators recently demonstrated that functional dyspepsia patients display impaired duodenal mucosal integrity and low-grade mucosal inflammation. As studies have also shown that functional dyspepsia patients present with an increased spontaneous duodenal acid exposure, the hypothesis of this study is that increased duodenal acid exposure results in increased duodenal permeability via mast cell activation. This will also induce activation of the duodenogastric reflex, resulting in gastric relaxation, eventually leading to the generation of dyspeptic symptoms. The general aim of this project is to assess the effect of mast cell inhibition on duodenal mucosal integrity and intragastric pressure of healthy volunteers after acid infusion in the duodenum.

The study will be a randomized, double-blind, cross-over study in 20 healthy volunteers and consists of 2 parts. (1) In the first part, 10 healthy volunteers will be perfused with acid (0.1N HCl) or 0.9% saline during 30 minutes at a rate of 5 mL/min with an interval of at least one month. During acid/saline perfusion, intragastric pressure will be measured with a high resolution manometry system to evaluate activation of the duodenogastric reflex. Dyspeptic symptoms will be scored 1 minute before and every 5 minutes during the infusion. After perfusion, endoscopy will be performed and duodenal biopsies will be obtained to evaluate mucosal integrity using Ussing chambers and by assessing the expression of cell-to-cell adhesion proteins (real-time PCR, immunofluorescence and western blot). (2) In the second part, 10 healthy volunteers will be perfused with acid after a placebo treatment and after treatment with the mast cell stabilizer disodium cromoglycate 100mg 4x2/day (with an interval of at least one month). The rest of the study continues as described in part 1.

Conditions

Dyspepsia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

placebo

mannitol

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

100mg 4x2 daily mannitol

disodium cromoglycate

disodium cromoglycate

Group Type: ACTIVE_COMPARATOR

Nalcrom

Intervention Type: DRUG

Drug: disodium cromoglycate 100mg 4x2 daily

Other Names:

• Nalcrom

Interventions

Nalcrom

Drug: disodium cromoglycate 100mg 4x2 daily

Other Names:

• Nalcrom

Intervention Type: DRUG

placebo

100mg 4x2 daily mannitol

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• healthy

Exclusion Criteria

• - refused informed consent
• pregnant women or women who are breastfeeding
• symptoms or history of gastrointestinal disease
• diabetes mellitus
• coagulation disorders/anticoagulant therapy
• first degree relatives with celiac disease, Crohn's disease or type I diabetes mellitus
• taking antihistamines, ketotifen, cromoglycate, acetylsalicylates, NSAIDs, anticholinergics, theophylline, β2-agonists, codeine or opioid derivatives 2 weeks prior to the study
• taking steroid or immunosuppressive drugs 6 months prior to the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven Campus Gasthuisberg O&N1

Leuven, Vlaams Brabant, Belgium

Countries

Belgium

Other Identifiers

2015-000244-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

S56881

Identifier Type: -

Identifier Source: org_study_id