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

NCT ID: NCT01269788

Last Updated: 2012-03-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

144 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-08-31

Study Completion Date

2011-08-31

Brief Summary

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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.

Detailed Description

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Conditions

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Non-erosive Reflux Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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pH positive-omeprazole

Group Type ACTIVE_COMPARATOR

Omeprazole

Intervention Type DRUG

20 mg , oral , daily 30 mins before breakfast, for 6 weeks

pH positive-placebo

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

oral , daily 30 mins before breakfast, for 6 weeks

pH positive-fluoxetine

Group Type ACTIVE_COMPARATOR

Fluoxetine

Intervention Type DRUG

20 mg , oral , daily 30 mins before breakfast, for 6 weeks

pH negative-omeprazole

Group Type ACTIVE_COMPARATOR

Omeprazole

Intervention Type DRUG

20 mg , oral , daily 30 mins before breakfast, for 6 weeks

pH negative-fluoxetine

Group Type ACTIVE_COMPARATOR

Fluoxetine

Intervention Type DRUG

20 mg , oral , daily 30 mins before breakfast, for 6 weeks

pH negative-placebo

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

oral , daily 30 mins before breakfast, for 6 weeks

Interventions

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Fluoxetine

20 mg , oral , daily 30 mins before breakfast, for 6 weeks

Intervention Type DRUG

Omeprazole

20 mg , oral , daily 30 mins before breakfast, for 6 weeks

Intervention Type DRUG

placebo

oral , daily 30 mins before breakfast, for 6 weeks

Intervention Type DRUG

Omeprazole

20 mg , oral , daily 30 mins before breakfast, for 6 weeks

Intervention Type DRUG

Fluoxetine

20 mg , oral , daily 30 mins before breakfast, for 6 weeks

Intervention Type DRUG

placebo

oral , daily 30 mins before breakfast, for 6 weeks

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tehran University of Medical Sciences

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Seyed Amir Mirbagheri, MD

Role: STUDY_CHAIR

Department of Internal Medicine, Faculty of medicine, Tehran university of medical sciences

Mohammad Reza Ostovaneh, MD,MPH

Role: PRINCIPAL_INVESTIGATOR

Tehran University of Medical Sciences

Arash Etemadi, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Tehran University of Medical Sciences

Yasin Farrokhi Khajeh Pasha, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Tehran University of Medical Sciences

Behtash Saeidi, MD

Role: PRINCIPAL_INVESTIGATOR

Tehran University of Medical Sciences

Kaveh Hajifathalian, MD

Role: PRINCIPAL_INVESTIGATOR

Tehran University of Medical Sciences

Akbar Fotouhi, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Tehran University of Medical Sciences

Seyed Mahmoud Eshagh hosseini, MD

Role: PRINCIPAL_INVESTIGATOR

Tehran University of Medical Sciences

Locations

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

Tehran, Tehran Province, Iran

Site Status

Countries

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Iran

References

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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. doi: 10.1038/ajg.2009.49.

Reference Type BACKGROUND
PMID: 19262544 (View on PubMed)

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. doi: 10.1046/j.1365-2036.2003.01423.x.

Reference Type BACKGROUND
PMID: 12622762 (View on PubMed)

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. doi: 10.1111/j.1365-2036.2005.02611.x.

Reference Type BACKGROUND
PMID: 16042660 (View on PubMed)

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. doi: 10.1016/s1542-3565(04)00288-5.

Reference Type BACKGROUND
PMID: 15290657 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8420248 (View on PubMed)

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. doi: 10.1111/j.1365-2036.2006.02798.x.

Reference Type BACKGROUND
PMID: 16483268 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8078547 (View on PubMed)

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. doi: 10.1097/00004836-199904000-00008.

Reference Type BACKGROUND
PMID: 10192608 (View on PubMed)

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. doi: 10.1067/mhj.2000.108514.

Reference Type BACKGROUND
PMID: 10966532 (View on PubMed)

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. doi: 10.1111/j.1365-2036.2006.02772.x.

Reference Type BACKGROUND
PMID: 16422995 (View on PubMed)

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. doi: 10.1007/s11136-004-9567-x.

Reference Type BACKGROUND
PMID: 15651544 (View on PubMed)

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. doi: 10.1111/j.1365-2036.2009.04013.x. Epub 2009 Apr 8.

Reference Type BACKGROUND
PMID: 19392864 (View on PubMed)

Ostovaneh MR, Saeidi B, Hajifathalian K, Farrokhi-Khajeh-Pasha Y, Fotouhi A, Mirbagheri SS, Emami H, Barzin G, Mirbagheri SA. Comparing omeprazole with fluoxetine for treatment of patients with heartburn and normal endoscopy who failed once daily proton pump inhibitors: double-blind placebo-controlled trial. Neurogastroenterol Motil. 2014 May;26(5):670-8. doi: 10.1111/nmo.12313. Epub 2014 Feb 7.

Reference Type DERIVED
PMID: 24533896 (View on PubMed)

Other Identifiers

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89-02-30-10638

Identifier Type: -

Identifier Source: org_study_id

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