Official Title: “Role of Pain Modulation in GERD Patients Who Failed Standard Dose PPI”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2009

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.

Intervention(s) in this Clinical Trial

• Drug: Rabeprazole 20mg, placebo dinner and bedtime
  • Breakfast study medication - Rabeprazole 20mg, matching placebo at dinner , Placebo for tricyclic antidepressant at bedtime
• Drug: Rabeprazole 20 mg two times, Placebo at bedtime
  • Breakfast & Dinner study medication - Rabeprazole, placebo for tricyclic antidepressant at bedtime
• Drug: Rabeprazole 20mg,placebo dinner ,Low dose Tricyclic Antidepressant
  • Rabeprazole (Breakfast) study medication, dinner placebo medication, tricyclic antidepressant at bedtime

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: 1
  • AciPhex 20 mg BID and once daily placebo
• Placebo Comparator: 2
  • AcipHex 20 mg once daily and BID placebo
• Placebo Comparator: 3
  • AcipHex 20 mg once daily, placebo once daily and nortriptyline once daily

Primary Measures

• Evaluate the role of pain modulation in GERD patients who fail to obtain clinical relief with standard dose (once daily) PPI. We will compare the efficacy of 1) standard dose PPI plus low-dose TCA to 2) double dose PPI to 3) standard dose PPI and placebo
  • Time Frame: Symptom control after 6 weeks of treatment
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Department of Veterans Affairs

Overall Clinical Trial Officials and Contacts

Ronnie Fass, MD Principal Investigator Southern Arizona VA Health Care System, Tucson  

Overall Contact: Marcia Willis, BA CCRC  marcia.willis@va.gov

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00539240

Study ID Number: CLIN-022-04F

ClinicalTrials.gov Identifier: NCT00539240

Health Authority: United States: Federal Government