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

Sponsor

Tehran University of Medical Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT01269788

Collaborator

(none)

144

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Non-erosive Reflux Disease	Drug: Fluoxetine Drug: Omeprazole Drug: placebo Drug: Omeprazole Drug: Fluoxetine Drug: placebo	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, 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

Study Start Date :

Aug 1, 2010

Actual Primary Completion Date :

Aug 1, 2011

Actual Study Completion Date :

Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

investigator-reported symptom severity [6 weeks]
symptom severity at beginning and 6 weeks after the study ,assessed by the standard questionnaire

Secondary Outcome Measures

patient-reported symptom severity [6 weeks]
symptom severity reported by the patient in daily diary
heartburn-free days [6 weeks]
percentage of 24-h heartburn-free days (days with neither daytime nor nighttime heartburn) during treatment assessed by daily diary

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	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