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.

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.