Role of Pain Modulation in GERD Patients Who Failed Standard Dose PPI
Condition: Gastroesophageal Reflux Disease
MeSH terms: Gastroesophageal Reflux
Study type: Interventional
Phase: Phase 2/Phase 3

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.
    

Intervention name(s): Rabeprazole 20mg, placebo dinner and bedtime; Rabeprazole 20 mg two times, Placebo at bedtime; Rabeprazole 20mg,placebo dinner ,Low dose Tricyclic Antidepressant
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Breakfast study medication - Rabeprazole 20mg, matching placebo at dinner , Placebo for tricyclic antidepressant at bedtime; Breakfast & Dinner study medication - Rabeprazole, placebo for tricyclic antidepressant at bedtime; Rabeprazole (Breakfast) study medication, dinner placebo medication, tricyclic antidepressant at bedtime
Other intervention name(s): AcipHex; Aciphex; Nortriptyline and Aciphex
Intervention MeSH terms: Antidepressive Agents; Nortriptyline; Antidepressive Agents, Tricyclic; Rabeprazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: acid reflux; acid regurgitation; esophagitis; GERD; heartburn; pain; peptic