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

July 29, 2014 updated by: US Department of Veterans Affairs
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 Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

236

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85723
        • Southern Arizona VA Health Care System, Tucson

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Rabeprazole morning/evening placebo bedtime
AciPhex 20 mg BID and once daily placebo
Drug: Rabeprazole 20 mg two times, Placebo at bedtime
Breakfast & Dinner study medication - Rabeprazole, placebo for tricyclic antidepressant at bedtime
Other Names:
  • Aciphex
Placebo Comparator: Rabeprazole breakfast, placebo dinner and bedtime
AcipHex 20 mg once daily and BID placebo
Drug: Rabeprazole 20mg, placebo dinner and bedtime
Breakfast study medication - Rabeprazole 20mg, matching placebo at dinner , Placebo for tricyclic antidepressant at bedtime
Other Names:
  • AcipHex
Active Comparator: Rabeprazole breakfast, placebo dinner, nortriptyline bedtime
AcipHex 20 mg once daily, placebo once daily and nortriptyline once daily
Drug: Rabeprazole 20mg,placebo dinner ,Low dose Tricyclic Antidepressant
Rabeprazole (Breakfast) study medication, dinner placebo medication, tricyclic antidepressant at bedtime
Other Names:
  • Nortriptyline and Aciphex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Daytime Heartburn, Number of Days in Week Symptoms Intensity Score < 3 (Better)
Time Frame: 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
Symptom control after 6 weeks of treatment
Nighttime Heartburn, Number of Days in Week Symptom Activity Score <3 (Better) in Week 6 Compared to Baseline
Time Frame: 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
Symptom control after 6 weeks of treatment
Acid Regurgitation, Number of Days in Week Symptoms Intensity Score < 3 (Better)
Time Frame: 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
Symptom control after 6 weeks of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Health Related Quality of Life
Time Frame: 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.
end of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

US Department of Veterans Affairs

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2006

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

November 1, 2011

Study Registration Dates

First Submitted

October 3, 2007

First Submitted That Met QC Criteria

October 3, 2007

First Posted (Estimate)

October 4, 2007

Study Record Updates

Last Update Posted (Estimate)

August 18, 2014

Last Update Submitted That Met QC Criteria

July 29, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLIN-022-04F

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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