Prucalopride Treatment for Refractory Gastro-esophageal Reflux Disease

A Placebo-controlled Trial With Prucalopride for the Treatment of Typical Reflux Symptoms in Patients With Gastro-esophageal Reflux Disease With Incomplete Proton Pump Inhibitor Response

Up to date there is no placebo-controlled trial to investigate the effect of prucalopride in patients with proven refractory GERD. Therefore, to evaluate the efficacy of prucalopride on the improvement in symptom severity and reflux parameters, we will conduct a randomized, parallel, placebo-controlled, single-blind study. 60 patients with refractory GERD symptoms will receive either placebo or prucalopride (Resolor®) 2 mg for a period of 4 weeks. Symptom severity will be assessed by a validated reflux questionnaire (ReQuest) and reflux parameters (acid exposure time and number of reflux episodes) will be assessed by means of a 24 hour impedance-pH monitoring.

Study Overview

• Status: Unknown
• Conditions: GERD
• Intervention / Treatment: Drug: Prucalopride; Drug: Placebo Oral Tablet

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

Contacts and Locations

• Study Contact: Name: Hannelore Geysen; Phone Number: +32 (0)16 324921; Email: hannelore.geysen@kuleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
    • Contact: Hannelore Geysen; Phone Number: +32 (0)16 324921; Email: hannelore.geysen@kuleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 to 65 years old.
2. Patients must have proven reflux, documented either by the presence of esophagitis (≥ grade B) at upper endoscopy ("on" PPI b.i.d.) in the 24 months prior to inclusion or pathological reflux parameters (acid exposure time >4% or number of reflux episodes >40) on a 24 hour impedance-pH monitoring ("on" PPI b.i.d.) in the 6 months prior to inclusion.
3. History of typical GERD symptoms during PPI treatment, at least 3 times per week for 12 weeks.
4. Daily intake of PPI treatment 12 weeks prior to inclusion, with at least 8 weeks of b.i.d. therapy (at least 2*20mg of omeprazole or equivalent).
5. Sexually active women of child bearing potential participating in the study must use a medically acceptable form of contraception. Medically acceptable forms of contraception do not include oral contraceptives, due to expected diarrhea as side effect of prucalopride. Injectable or implantable methods, intrauterine devices, or properly used barrier contraception are acceptable forms of contraception.
6. Subjects must be capable of understanding and be willing to provide signed and dated written voluntary informed consent before any protocol-specific screening procedures are performed.

Exclusion Criteria:

1. Systemic diseases, known to affect esophageal motility.
2. Colitis ulcerosa, Crohn's disease, toxic megacolon.
3. Have a cardiovascular disease or QT c>450 ms
4. Severely decreased kidney function.
5. Severely decreased liver function.
6. Surgery in the thorax or in the upper part of the abdomen (appendectomy and cholecystectomy are allowed).
7. Number of stools >3 per day.
8. Major psychiatric disorder.
9. Treatment with prucalopride prior to the start of the study.
10. Concomitant use of medications such as: anticholinergics, baclofen or prokinetics.
11. Significant neurological, respiratory, hepatic, renal, hematological, cardiovascular, metabolic or gastrointestinal cerebrovascular disease as judged by the investigator.
12. Absence of PPI intake for at least 2 consecutive days in the 2 weeks prior to the screening.
13. Pregnancy or breast feeding.
14. History of poor compliance. History of/or current psychiatric illness that would interfere with ability to comply with protocol requirements or give informed consent.
15. History of alcohol or drug abuse that would interfere with ability to comply with protocol requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prucalopride; Prucalopride 2mg once a day as add-on for PPI 2x/d	Drug: Prucalopride; Prucalopride 2mg taken once a day as add-on to PPI (2x/d)
Placebo Comparator: Placebo; Placebo once a day as add-on for PPI 2x/d	Drug: Placebo Oral Tablet; Placebo tablet taken once a day as add-on to PPI (2x/d)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in acid exposure time	change in acid exposure time assessed by 24 hour impedance-pH monitoring.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in number of reflux episodes	change in number of reflux episodes assessed by 24 hour impedance-pH monitoring	4 weeks
Change in symptom severity	change in symptom severity assessed by a validated reflux questionnaire (ReQuest questionnaire and diaries)	4 weeks

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2019
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: April 10, 2018
• First Submitted That Met QC Criteria: September 17, 2018
• First Posted (Actual): September 18, 2018

Study Record Updates

• Last Update Posted (Actual): December 5, 2019
• Last Update Submitted That Met QC Criteria: December 4, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux; 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: S61035

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No