Clinical trial NCT00539240
Conditions: Gastroesophageal Reflux Disease
Keywords: acid reflux acid regurgitation esophagitis GERD heartburn pain peptic
Sponsor: US Department of Veterans Affairs
Start date: 2006-04-01; Completion date: 2011-11-01
Enrollment: 236 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this project is to compare the efficacy (how successful) 1) standard-dose proton pump inhibitor (PPI) (rabeprazole 20 mg once daily) (a medication that completely blocks the stomach from producing acid) plus low dose tricyclic antidepressant (nortriptyline 50mg) (TCA); 2) double-dose PPI (rabeprazole 20 mg twice a day); to 3) standard-dose PPI (rabeprazole 20mg once daily) and placebo (an inactive substance, like a sugar pill) to determine the relative symptom resolution and health-related quality of life in gastroesophageal reflux disease (a disease characterized by a burning sensation (heartburn) behind the breast bone caused by a backflow of stomach contents into the esophagus) (GERD) patients who fail standard-dose PPI and you will be randomly assigned (similar to flipping a coin) to one of the three groups.

Detailed description:
Failure of standard dose PPI to control GERD symptoms has been increasingly encountered in clinical practice (both primary care and sub-specialties) and has become one of the most challenging therapeutic dilemmas in GERD management. It has been estimated that up to 30% of the patients receiving PPI once daily will continue to report typical GERD symptoms \[1\]. Presently, increasing the PPI dose has been the standard of care in these patients \[2\]. However, success in relieving refractory GERD symptoms with such a therapeutic approach has been extremely limited, resulting in frustration of both the patient as well as the health care provided. Furthermore, patients who fail PPI will continue to seek medical attention and may undergo a variety of invasive or non-invasive tests, and thus consume already limited health care resources. Recent advancement in the understanding of the diverse composition of the different GERD groups as well as symptom generation has led to the recognition of alteration in pain perception as an important contributing factor for PPI failure in some and the presence of non-acid related stimuli in others \[3\].

This study will clarify for the first time the role of pain modulation in patients who failed standard dose of PPI. The clinical experience with doubling the PPI dose, which is the current standard of care, has been very limited and relatively disappointing. Additionally, this study may identify the group of PPI failure patients that may benefit from doubling the dose of PPI and the group that will benefit more from adding a pain modulator. This study is timely, has never been performed and addresses a prevalent emerging clinical dilemma in GI as well as primary care clinics.

Arms: arm 1: AciPhex 20 mg BID and once daily placebo arm 2: AcipHex 20 mg once daily and BID placebo arm 3: AcipHex 20 mg once daily, placebo once daily and nortriptyline once daily
Interventions: intervention 1: Rabeprazole 20mg, placebo dinner and bedtime intervention 2: Rabeprazole 20 mg two times, Placebo at bedtime intervention 3: Rabeprazole 20mg,placebo dinner ,Low dose Tricyclic Antidepressant
Intervention descriptions: intervention 1: Breakfast study medication - Rabeprazole 20mg, matching placebo at dinner , Placebo for tricyclic antidepressant at bedtime intervention 2: Breakfast \& Dinner study medication - Rabeprazole, placebo for tricyclic antidepressant at bedtime intervention 3: Rabeprazole (Breakfast) study medication, dinner placebo medication, tricyclic antidepressant at bedtime

Protocol documents: