Role of Pain Modulation in GERD Patients Who Failed Standard Dose Proton Pump Inhibitors (PPI)

Study Overview
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Brief Summary
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The main objective of this study is to evaluate the role of pain modulation in GERD patients who fail to obtain clinical relief with standard dose (once daily) PPI. The study will compare the efficacy of 1) standard dose PPI plus low-dose tricyclic antidepressant (TCA) to, 2) double dose PPI to, 3) standard dose PPI and placebo to determine the relative symptom resolution and health related quality of life in GERD patients who fail standard dose PPI and are randomly assigned to one of these three groups.

Detailed Description
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To evaluate the role of pain modulation in gastroesophageal reflux disease(GERD)patients who fail to obtain clinical relief with standard dose (once daily) proton pump inhibitor(PPI). The study will compare the efficacy; of 1)standard dose PPI plus low-dose tricyclic antidepressant (TCA) to, 2) double dose PPI to, 3) standard dose PPI and placebo to determine the relative symptom resolution and health related quality of life in GERD patients who fail standard dose PPI and are randomly assigned to one of these three groups.

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

Conditions
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Gastroesophageal Reflux Disease

Intervention / Treatment
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* Drug: Standard dose (once daily) PPI plus low-dose antidepressant
* Drug: Double dose PPI plus evening placebo
* Drug: Rabeprazole , placebo, placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Ages 18 to 75 At least two episodes of heartburn per week while on PPI once daily Able to communicate with the investigator and comply with the requirements of the study Subjects who give written informed consent after being given a full description of the study. Exclusion Criteria: Known allergy or intolerance to TCA Use of antidepressant or a diagnosis of depression 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, hematologic, endocrine, neurologic or psychiatric. Evidence or history of drug abuse within the past 6 months Erosive esophagitis, esophageal ulceration, peptic stricture, Barret'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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard dose (PPI) plus low dose TCA<br>Standard dose Rabeprazole(PPI) plus low dose tricyclic antidepressant(TCA) | Drug: Standard dose (once daily) PPI plus low-dose antidepressant<br>* 20 mg. rabeprazole plus low dose tricyclic antidepressant(TCA)<br>* Other names: Nortriptyline-TCA;|
| Active Comparator: Double dose PPI<br>Double dose proton pump inhibitor plus placebo | Drug: Double dose PPI plus evening placebo<br>* 20 mg. twice daily with a placebo<br>* Other names: Aciphex-PPI, rabeprazole;|
| Placebo Comparator: Standard dose PPI plus placebo x 2<br>Standard dose 20 mg. once daily plus Placebo before dinner and placebo before bedtime | Drug: Rabeprazole , placebo, placebo<br>* 20 mg rabeprazole(PPI) once daily -a.m. placebo -p.m. placebo -bedtime<br>* Other names: Nortriptyline-low-dose tricyclic antidepressant (TCA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom control after 6 weeks of treatment | To measure the outcome after 6 weeks of treatment | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of drop-outs due to poor symptom control | To measure the number of drop-outs due to poor symptom control. | 6 weeks | 
| Level of antacid consumption | To measure the level of antacid consumption due to poor symptom control. | 6 weeks | 
| Improvement in quality of life | To improve quality of life with GERD symptom control. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acid reflux studies, efficacy of PPI therapy, failing PPI therapy, GERD, Acid Reflux Disease