The Effect of Prucalopride (Resolor®) on Gastric Motor Function and Gastric Sensitivity

Functional Dyspepsia-Postprandial Distress Syndrome (FD-PDS), is characterized by meal-related symptoms such as early satiation and postprandial fullness. Disturbances of gastric motor function have been implicated the pathogenesis of PDS symptoms, and hence, motility modifying agents are considered for the treatment of PDS. Prucalopride (Resolor®), a highly selective 5-TH4 receptor agonist which stimulates gastrointestinal motility throughout the GI tract, is currently approved for the treatment of chronic constipation. The objective of this study was to evaluate the effect of prucalopride on gastric sensorimotor function in healthy volunteers (HV). Methods A total of 17 HV (59% females, mean age 29.4±2.7 years) underwent a barostat and intragastric pressure (IGP) measurements after treatment with placebo or prucalopride (2 mg) in a single blinded cross-over fashion. Isobaric distentions with stepwise increments of 2 mm Hg starting from minimal distending pressure (MDP) and scoring of intensities of gastric sensations (0-6: pain) were used to determine gastric compliance and sensitivity. Gastric accommodation (GA) was quantified as the difference (delta) in intra-balloon volume 30 min before and 60 min after ingestion of 200 ml of a nutrient drink (ND) (1.5 kcal mL(-1)). GA measured by IGP was quantified as the drop of IGP from baseline during the intragastric infusion of ND until maximal satiation. During all tests, epigastric symptoms were scored every 5 minutes.

Study Overview

• Status: Completed
• Conditions: Dyspepsia; Gastrointestinal Motility Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Prucalopride

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers, male and females, between 18-60 years old

Exclusion Criteria:

Subjects that:

• They are older than 60 years old.
• Have severely decreased kidney function.
• Have severely decreased liver function.
• Have severe heart disease, for example a history of irregular heartbeats, angina or heart attack.
• Have severe lung disease.
• Have severe psychiatric illness or neurological illness.
• Have any gastrointestinal disease
• Women that are pregnant or breastfeeding.
• Have a rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption (Resolor tablets contain lactose).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo is an opaque empty gel capsule obtained from the UZ Gasthuisberg pharmacy. These capsules are composed of 100% gelatine that will rapidly dissolve (disintegration time is 15 minutes) in the stomach without affecting the gastric motor function.	Drug: Placebo; Orally administered
Experimental: Prucalopride; 2 mg, Resolor®, Shire, Belgium Prucalopride (2 mg) is rapidly absorbed; after a single oral dose of 2 mg Cmax was attained in 2-3 hours. The absolute oral bioavailability is >90%. Concomitant intake of food does not influence the oral bioavailability of prucalopride.	Drug: Prucalopride; Orally administered; Other Names: Resolor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effect of prucalopride on gastric accommodation with gastric barostat technique	Gastric barostat: The gastric balloon will be distended at the minimal distending pressure plus 2 mmHg for 90 minutes. During this time, the subject will score their gastric satiation (0-5) every 5 minutes. After the first 30 minutes, the subject will be asked to drink a liquid meal (20 ml Nutridrink, Nutricia; 630 KJ, 6 g proteins, 18.4 g carbohydrates, and 5.8 g lipids per 100 mL) to induce gastric accommodation.	90 minutes
The effect of prucalopride on gastric accommodation with intragastric pressure measurement technique	Intragastric pressure measurement with high resolution manometry. A manometry probe, a small, flexible tube, will be passed through the nose into the stomach of the subject. The probe contains 36 channels that measure pressure. The manometry probe will be positioned in the fundus and the position will be then verified by fluoroscopy. To infuse the nutrient drink directly into the stomach, a second infusion catheter will be positioned through the mouth of the subject. nutrient drink (Nutridrink, Nutricia) will be infused directly into the stomach at a constant speed of 60 millilitres per minute. Infusion is stopped when the subject reports maximal satiation.	60 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analog Score for sensitivity	Gastric sensitivity will be done by means of step-wise distention of the gastric barostat with Visual Analog Score for sensitivity	120 minutes
The effect of prucalopride on gastric compliance	Gastric compliance of the gastric wall will be assessed with step-wise distention of the gastric balloon	120 minutes
The effect of prucalopride on nutrient tolerance	The amount of ingested calories will be assessed during intragastric infusion of a nutrient drink will be evaluated	30 minutes

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

General Publications

• Carbone F, Vanuytsel T, Tack J. The effect of prucalopride on gastric sensorimotor function and satiation in healthy volunteers. Neurogastroenterol Motil. 2021 Aug;33(8):e14083. doi: 10.1111/nmo.14083. Epub 2021 Feb 2.

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): October 3, 2016

Study Registration Dates

• First Submitted: August 24, 2018
• First Submitted That Met QC Criteria: June 11, 2020
• First Posted (Actual): June 12, 2020

Study Record Updates

• Last Update Posted (Actual): October 26, 2021
• Last Update Submitted That Met QC Criteria: October 25, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: gastric accommodation; nutrient tolerance; gastric sensitivity; gastric compliance
• Additional Relevant MeSH Terms: Immune System Diseases; Signs and Symptoms, Digestive; Hypersensitivity; Dyspepsia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Serotonin Agents; Serotonin Receptor Agonists; Laxatives; Serotonin 5-HT4 Receptor Agonists; Prucalopride
• Other Study ID Numbers: S55741

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