Compare How Effective Standard Dose Proton Pump Inhibitor (PPI) and Low Dose Tricyclic Antidepressant and Double Dose PPI to Standard Dose PPI and Placebo - Full Text View

Sponsor:	Department of Veterans Affairs
Information provided by:	Department of Veterans Affairs
ClinicalTrials.gov Identifier:	NCT00539240

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 II Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Role of Pain Modulation in GERD Patients Who Failed Standard Dose PPI

Resource links provided by NLM:

MedlinePlus related topics: Antidepressants GERD Heartburn

Drug Information available for: E 3810

U.S. FDA Resources

Further study details as provided by Department of Veterans Affairs:

Primary Outcome 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	150
Study Start Date:	April 2006
Estimated Study Completion Date:	May 2010
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator AciPhex 20 mg BID and once daily placebo	Drug: Rabeprazole 20mg, placebo dinner and bedtime Breakfast study medication - Rabeprazole 20mg, matching placebo at dinner , Placebo for tricyclic antidepressant at bedtime
2: Placebo Comparator AcipHex 20 mg once daily and BID placebo	Drug: Rabeprazole 20 mg two times, Placebo at bedtime Breakfast & Dinner study medication - Rabeprazole, placebo for tricyclic antidepressant at bedtime
3: Placebo Comparator 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

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

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

Contacts

Contact: Marcia Willis, BA CCRC		marcia.willis@va.gov
Contact: Phyllis J Houston, AAS	(520) 792-1450	Phyllis.Houston@va.gov

Locations

United States, Arizona
Southern Arizona VA Health Care System, Tucson	Recruiting
Tucson, Arizona, United States, 85723
Contact: Marcia Willis, BA CCRC marcia.willis@va.gov
Contact: Sheila Ojendyk (520) 792-1450 ext 5537 sheila.ojendyk@va.gov
Principal Investigator: Ronnie Fass, MD

Sponsors and Collaborators

Department of Veterans Affairs

Investigators

Principal Investigator:

Ronnie Fass, MD

Southern Arizona VA Health Care System, Tucson

More Information

Publications:

Richter JE, Campbell DR, Kahrilas PJ, Huang B, Fludas C. Lansoprazole compared with ranitidine for the treatment of nonerosive gastroesophageal reflux disease. Arch Intern Med. 2000 Jun 26;160(12):1803-9.

Kahrilas PJ, Falk GW, Johnson DA, Schmitt C, Collins DW, Whipple J, D'Amico D, Hamelin B, Joelsson B. Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial. The Esomeprazole Study Investigators. Aliment Pharmacol Ther. 2000 Oct;14(10):1249-58.

Fass R, Murthy U, Hayden CW, Malagon IB, Pulliam G, Wendel C, Kovacs TO. Omeprazole 40 mg once a day is equally effective as lansoprazole 30 mg twice a day in symptom control of patients with gastro-oesophageal reflux disease (GERD) who are resistant to conventional-dose lansoprazole therapy-a prospective, randomized, multi-centre study. Aliment Pharmacol Ther. 2000 Dec;14(12):1595-603.

Fass R, Fennerty MB, Vakil N. Nonerosive reflux disease--current concepts and dilemmas. Am J Gastroenterol. 2001 Feb;96(2):303-14. Review.

Carlsson R, Dent J, Watts R, Riley S, Sheikh R, Hatlebakk J, Haug K, de Groot G, van Oudvorst A, Dalvag A, Junghard O, Wiklund I. Gastro-oesophageal reflux disease in primary care: an international study of different treatment strategies with omeprazole. International GORD Study Group. Eur J Gastroenterol Hepatol. 1998 Feb;10(2):119-24.

Responsible Party:	Department of Veterans Affairs ( Fass, Ronnie - Principal Investigator )
Study ID Numbers:	CLIN-022-04F
Study First Received:	October 3, 2007
Last Updated:	January 13, 2010
ClinicalTrials.gov Identifier:	NCT00539240 History of Changes
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:

Molecular Mechanisms of Pharmacological Action
Gastrointestinal Diseases
Gastrointestinal Agents
Psychotropic Drugs
Enzyme Inhibitors
Gastroesophageal Reflux
Pharmacologic Actions
Antidepressive Agents, Tricyclic
Esophageal Motility Disorders

Deglutition Disorders
Digestive System Diseases
Proton Pump Inhibitors
Therapeutic Uses
Anti-Ulcer Agents
Esophageal Diseases
Central Nervous System Agents
Antidepressive Agents
Rabeprazole

ClinicalTrials.gov processed this record on February 08, 2010