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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00539240
First received: October 3, 2007
Last updated: July 29, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Gastroesophageal Reflux Disease
Drug: Rabeprazole 20mg, placebo dinner and bedtime
Drug: Rabeprazole 20 mg two times, Placebo at bedtime
Drug: Rabeprazole 20mg,placebo dinner ,Low dose Tricyclic Antidepressant
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Role of Pain Modulation in GERD Patients Who Failed Standard Dose PPI

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Daytime Heartburn, Number of Days in Week Symptoms Intensity Score < 3 (Better) [ Time Frame: Symptom control after 6 weeks of treatment ] [ Designated as safety issue: No ]
    the number of days with Symptom Intensity Score < 3 (better) for daytime heartburn during week 6 as compared to baseline

  • 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 ] [ Designated as safety issue: No ]
    the number of days with Symptom Intensity Score < 3 (better) for nighttime heartburn during week 6 as compared to baseline

  • Acid Regurgitation, Number of Days in Week Symptoms Intensity Score < 3 (Better) [ Time Frame: Symptom control after 6 weeks of treatment ] [ Designated as safety issue: No ]
    the number of days with Symptom Intensity Score < 3 (better) for acid regurgitation during week 6 as compared to baseline


Secondary Outcome Measures:
  • Health Related Quality of Life [ Time Frame: end of study ] [ Designated as safety issue: No ]
    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.


Enrollment: 236
Study Start Date: April 2006
Study Completion Date: November 2011
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: Nortriptyline and Aciphex

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00539240

Locations
United States, Arizona
Southern Arizona VA Health Care System, Tucson
Tucson, Arizona, United States, 85723
Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00539240     History of Changes
Other Study ID Numbers: CLIN-022-04F
Study First Received: October 3, 2007
Results First Received: February 7, 2014
Last Updated: July 29, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
acid reflux
acid regurgitation
esophagitis
GERD
heartburn
pain
peptic

Additional relevant MeSH terms:
Gastroesophageal Reflux
Deglutition Disorders
Digestive System Diseases
Esophageal Diseases
Esophageal Motility Disorders
Gastrointestinal Diseases
Antidepressive Agents
Antidepressive Agents, Tricyclic
Nortriptyline
Rabeprazole
Adrenergic Agents
Adrenergic Uptake Inhibitors
Anti-Ulcer Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Proton Pump Inhibitors
Psychotropic Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014