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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tehran University of Medical Sciences
ClinicalTrials.gov Identifier:
NCT01269788
First received: December 21, 2010
Last updated: March 5, 2012
Last verified: March 2012
  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:


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
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: 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:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 July 24, 2014