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

Gastroesophageal Reflux Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00539240
• Other study ID #: CLIN-022-04F
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: October 3, 2007
• Last updated: July 29, 2014
• Start date: April 2006
• Est. completion date: November 2011

Study information

• Verified date: July 2014
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 236
• Est. completion date: November 2011
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastroesophageal Reflux
• Gastroesophageal Reflux Disease

Intervention

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

Locations

Country	Name	City	State
United States	Southern Arizona VA Health Care System, Tucson	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Daytime Heartburn, Number of Days in Week Symptoms Intensity Score < 3 (Better)	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	No
Primary	Nighttime Heartburn, Number of Days in Week Symptom Activity Score <3 (Better) in Week 6 Compared to Baseline	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	No
Primary	Acid Regurgitation, Number of Days in Week Symptoms Intensity Score < 3 (Better)	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	No
Secondary	Health Related Quality of Life	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	No