Comparing Omeprazole With Fluoxetine for Treatment of Non Erosive Reflux Disease and Its Subgroups: a Double-blind Placebo-controlled Clinical Trial - Full Text View

Purpose

Gastro-esophageal reflux disease (GERD) is highly prevalent, affecting up to 20% of the adult population in North America. Up to 70% of GERD patients have non-erosive reflux disease (NERD), a term used to describe symptoms suggestive of GERD in patients with no endoscopic evidence of erosive esophagitis. NERD represents a heterogeneous group of patients whom are sub classified according to 24 hours-PH monitoring results and also symptom-acid association analysis(Symptom Index,SI).

Treatment of NERD can be a challenge for clinicians. According to the many studies , the pooled rate for symptomatic response after a period of proton pomp inhibitor(PPIs)therapy as the most frequently used drug, in NERD patients is lower than for erosive esophagitis patients. It is also shown that acid exposure is much lower in NERD patients than those with erosive esophagitis and NERD patients are less likely to exhibit a strong association between heartburn symptoms and acid reflux events than patients with erosive oesophagitis.

Furthermore, beside the high economic burden, there are concerns about the adverse effects of long time administration of PPIs.

Several hypothesis has been proposed to describe low response rate of NERD patients to PPIs. One of the most acceptable theories is that patients with anxiety or depression and psychological problems are at an increased risk of developing reflux symptoms. On the other hand, pain modulators such as sertraline, a selective serotonin reuptake inhibitor(SSRI), and other antidepressants have been shown to improve symptoms in patients with functional gastrointestinal disorders like non cardiac chest pain.

According to the above-mentioned tips, the investigators hypothesize that antidepressants like fluoxetine, as an SSRI, may have beneficial effects in improving symptoms of NERD patients.

The purpose of this study is to compare the effect of omeprazole with fluoxetine and placebo for treatment of NERD patients and its subgroups who all experience reflux symptoms and have normal endoscopic findings.

Condition	Intervention	Phase
Non-erosive Reflux Disease	Drug: Fluoxetine Drug: Omeprazole Drug: placebo	Phase 2 Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Comparing Omeprazole With Fluoxetine for Treatment of Non Erosive Reflux Disease and Its Subgroups: a Double-blind Placebo-controlled Clinical Trial

Resource links provided by NLM:

MedlinePlus related topics: Antidepressants GERD Heartburn

Drug Information available for: Fluoxetine Fluoxetine hydrochloride Omeprazole Omeprazole magnesium Esomeprazole Esomeprazole Sodium Esomeprazole magnesium

U.S. FDA Resources

Further study details as provided by Tehran University of Medical Sciences:

Primary Outcome Measures:

investigator-reported symptom severity [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
symptom severity at beginning and 6 weeks after the study ,assessed by the standard questionnaire

Secondary Outcome Measures:

patient-reported symptom severity [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
symptom severity reported by the patient in daily diary
heartburn-free days [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
percentage of 24-h heartburn-free days (days with neither daytime nor nighttime heartburn) during treatment assessed by daily diary

Enrollment:	144
Study Start Date:	August 2010
Study Completion Date:	August 2011
Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: pH positive-omeprazole	Drug: Omeprazole 20 mg , oral , daily 30 mins before breakfast, for 6 weeks
Placebo Comparator: pH positive-placebo	Drug: placebo oral , daily 30 mins before breakfast, for 6 weeks
Active Comparator: pH positive-fluoxetine	Drug: Fluoxetine 20 mg , oral , daily 30 mins before breakfast, for 6 weeks
Active Comparator: pH negative-omeprazole	Drug: Omeprazole 20 mg , oral , daily 30 mins before breakfast, for 6 weeks
Active Comparator: pH negative-fluoxetine	Drug: Fluoxetine 20 mg , oral , daily 30 mins before breakfast, for 6 weeks
Placebo Comparator: pH negative-placebo	Drug: placebo oral , daily 30 mins before breakfast, for 6 weeks

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

age above 18 and below 60 years old
experiencing heartburn during last 6 months before inclusion
experiencing heartburn during at least 4 of 7 days before inclusion
presence of normal mucosa in upper gastrointestinal(GI) endoscopy which has been documented during 7 days before inclusion provided that the patient has not administered any PPI during last 30 days before inclusion

Exclusion Criteria:

inability to undergone upper GI endoscopy or PH monitoring
presence of barret's esophagus or erosive esophagitis in upper GI endoscopy
presence of active peptic ulcer disease or any disease which affects the absorption of drugs such as inflammatory bowel disease
past history of esophageal or gastric surgery
esophageal stricture which needs dilation
administration of proton pomp inhibitors during 30 days before inclusion to the study
administration of H2 blockers, anticholinergics, sucralfate and pro-kinetics during the assessments for eligibility and also during the study
long time administration of non-steroidal anti-inflammatory drugs (NSAIDs)
administration of neuroleptic or antidepressant drugs during 30 days before inclusion to the study
known allergy to PPIs or SSRIs
presence of significant systemic disease such as scleroderma , diabet mellitus , peripheral and autonomic neuropathies and ...
pregnancy for females
presence of known psychiatric disorder such as depression , panic disorder or drug addiction according to the DSM-IV criteria

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01269788

Locations

Iran, Islamic Republic of
Gasterointestinal endoscopy ward, Amir Alam hospital, Tehran university of medical sciences
Tehran, Iran, Islamic Republic of

Sponsors and Collaborators

Tehran University of Medical Sciences

Investigators

Study Chair:	Seyed Amir Mirbagheri, MD	Department of Internal Medicine, Faculty of medicine, Tehran university of medical sciences
Principal Investigator:	Mohammad Reza Ostovaneh, MD,MPH	Tehran University of Medical Sciences
Principal Investigator:	Arash Etemadi, MD, PhD	Tehran University of Medical Sciences
Principal Investigator:	Yasin Farrokhi Khajeh Pasha, MD, MPH	Tehran University of Medical Sciences
Principal Investigator:	Behtash Saeidi, MD	Tehran University of Medical Sciences
Principal Investigator:	Kaveh Hajifathalian, MD	Tehran University of Medical Sciences
Principal Investigator:	Akbar Fotouhi, MD, PhD	Tehran University of Medical Sciences
Principal Investigator:	Seyed Mahmoud Eshagh hosseini, MD	Tehran University of Medical Sciences

More Information

Publications:

Heidelbaugh JJ, Goldberg KL, Inadomi JM. Overutilization of proton pump inhibitors: a review of cost-effectiveness and risk [corrected]. Am J Gastroenterol. 2009 Mar;104 Suppl 2:S27-32. Review. Erratum in: Am J Gastroenterol. 2009 Apr;104(4):1072. Am J Gastroenterol. 2009 Mar;104(2 Suppl):S39.

Martinez SD, Malagon IB, Garewal HS, Cui H, Fass R. Non-erosive reflux disease (NERD)--acid reflux and symptom patterns. Aliment Pharmacol Ther. 2003 Feb 15;17(4):537-45.

Raghunath AS, O'Morain C, McLoughlin RC. Review article: the long-term use of proton-pump inhibitors. Aliment Pharmacol Ther. 2005 Aug;22 Suppl 1:55-63. Review.

Dean BB, Gano AD Jr, Knight K, Ofman JJ, Fass R. Effectiveness of proton pump inhibitors in nonerosive reflux disease. Clin Gastroenterol Hepatol. 2004 Aug;2(8):656-64. Review.

Bradley LA, Richter JE, Pulliam TJ, Haile JM, Scarinci IC, Schan CA, Dalton CB, Salley AN. The relationship between stress and symptoms of gastroesophageal reflux: the influence of psychological factors. Am J Gastroenterol. 1993 Jan;88(1):11-9.

DeVault KR. Review article: the role of acid suppression in patients with non-erosive reflux disease or functional heartburn. Aliment Pharmacol Ther. 2006 Mar;23 Suppl 1:33-9. Review.

Venes DJ. Imipramine in patients with chest pain despite normal coronary angiograms. N Engl J Med. 1994 Sep 29;331(13):882; author reply 882-3. No abstract available.

Handa M, Mine K, Yamamoto H, Hayashi H, Tsuchida O, Kanazawa F, Kubo C. Antidepressant treatment of patients with diffuse esophageal spasm: a psychosomatic approach. J Clin Gastroenterol. 1999 Apr;28(3):228-32.

Varia I, Logue E, O'connor C, Newby K, Wagner HR, Davenport C, Rathey K, Krishnan KR. Randomized trial of sertraline in patients with unexplained chest pain of noncardiac origin. Am Heart J. 2000 Sep;140(3):367-72.

Broekaert D, Fischler B, Sifrim D, Janssens J, Tack J. Influence of citalopram, a selective serotonin reuptake inhibitor, on oesophageal hypersensitivity: a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2006 Feb 1;23(3):365-70.

Rentz AM, Kahrilas P, Stanghellini V, Tack J, Talley NJ, de la Loge C, Trudeau E, Dubois D, Revicki DA. Development and psychometric evaluation of the patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) in patients with upper gastrointestinal disorders. Qual Life Res. 2004 Dec;13(10):1737-49.

Fass R, Chey WD, Zakko SF, Andhivarothai N, Palmer RN, Perez MC, Atkinson SN. Clinical trial: the effects of the proton pump inhibitor dexlansoprazole MR on daytime and nighttime heartburn in patients with non-erosive reflux disease. Aliment Pharmacol Ther. 2009 Jun 15;29(12):1261-72. Epub 2009 Apr 8.

Responsible Party:	Tehran University of Medical Sciences
ClinicalTrials.gov Identifier:	NCT01269788 History of Changes
Other Study ID Numbers:	89-02-30-10638
Study First Received:	December 21, 2010
Last Updated:	March 5, 2012
Health Authority:	Iran: Ethics Committee Iran: Ministry of Health

Keywords provided by Tehran University of Medical Sciences:

non-erosive reflux disease
heartburn
functional
Antidepressive Agents, Second-Generation
Proton Pump Inhibitors

Additional relevant MeSH terms:

Gastroesophageal Reflux
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Antidepressive Agents
Fluoxetine
Antidepressive Agents, Second-Generation
Omeprazole
Proton Pump Inhibitors
Psychotropic Drugs

Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs
Anti-Ulcer Agents
Gastrointestinal Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 19, 2013