Role of Pain Modulation in GERD Patients Who Failed Standard Dose PPI

Phase 2

Completed

Conditions: Gastroesophageal Reflux Disease

Interventions: Drug: Rabeprazole 20mg,placebo dinner ,Low dose Tricyclic Antidepressant
Drug: Rabeprazole 20 mg two times, Placebo at bedtime
Drug: Rabeprazole 20mg, placebo dinner and bedtime

Registration Number: NCT00539240

Lead Sponsor: US Department of Veterans Affairs

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 236

Inclusion Criteria

Currently being treated with a PPI, but continue to experience GERD symptoms (such as heartburn) at least 2 times per week.

Exclusion Criteria

Known allergy or intolerance to TCA
History of serious arrhythmia or use of anti-arrhythmics
History of seizures
Subjects with significant co-morbidity, e.g., cardiovascular, respiratory, urogenital, renal, gastrointestinal, hepatic, hematological, endocrine, neurologic or psychiatric
With evidence or history of drug abuse within the past 6 months
Erosive esophagitis, esophageal ulceration, peptic stricture, Barrett's esophagus or adenocarcinoma of the esophagus on endoscopy
History of esophagogastric surgery
Gastric or duodenal lesions (ulcer, tumor, etc.)
Women who are pregnant or of childbearing age who are not on contraception
Patients who are unwilling or unable to provide informed consent
Insulin dependent diabetes

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rabeprazole breakfast, placebo dinner, nortriptyline bedtime	Rabeprazole 20mg,placebo dinner ,Low dose Tricyclic Antidepressant	AcipHex 20 mg once daily, placebo once daily and nortriptyline once daily
Rabeprazole morning/evening placebo bedtime	Rabeprazole 20 mg two times, Placebo at bedtime	AciPhex 20 mg BID and once daily placebo
Rabeprazole breakfast, placebo dinner and bedtime	Rabeprazole 20mg, placebo dinner and bedtime	AcipHex 20 mg once daily and BID placebo

Primary Outcome Measures

Name	Time	Method
Daytime Heartburn, Number of Days in Week Symptoms Intensity Score < 3 (Better)	Symptom control after 6 weeks of treatment	the number of days with Symptom Intensity Score \< 3 (better) for daytime heartburn during week 6 as compared to baseline
Acid Regurgitation, Number of Days in Week Symptoms Intensity Score < 3 (Better)	Symptom control after 6 weeks of treatment	the number of days with Symptom Intensity Score \< 3 (better) for acid regurgitation during week 6 as compared to baseline
Nighttime Heartburn, Number of Days in Week Symptom Activity Score <3 (Better) in Week 6 Compared to Baseline	Symptom control after 6 weeks of treatment	the number of days with Symptom Intensity Score \< 3 (better) for nighttime heartburn during week 6 as compared to baseline

Secondary Outcome Measures

Name	Time	Method
Health Related Quality of Life	end of study	SF-36 Physical Component Score (higher number better quality of life), is a measure of overall physical quality of life distinct from mental health. The range is 0 - 100. It has been adjusted to US national norms so that a score of 50 corresponds to the national mean.