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

NCT01269788 | Completed Phase 2

• 1 other identifier: 89-02-30-10638
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-erosive Reflux Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• investigator-reported symptom severity

  symptom severity at beginning and 6 weeks after the study ,assessed by the standard questionnaire

  6 weeks

Secondary Outcomes (2)

• patient-reported symptom severity

  6 weeks

• heartburn-free days

  6 weeks

Study Arms (6)

pH positive-omeprazole

ACTIVE COMPARATOR

Drug: Omeprazole

pH positive-placebo

PLACEBO COMPARATOR

Drug: placebo

pH positive-fluoxetine

ACTIVE COMPARATOR

Drug: Fluoxetine

pH negative-omeprazole

ACTIVE COMPARATOR

Drug: Omeprazole

pH negative-fluoxetine

ACTIVE COMPARATOR

Drug: Fluoxetine

pH negative-placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

placebo DRUG

oral , daily 30 mins before breakfast, for 6 weeks

pH positive-placebo

Omeprazole DRUG

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

pH positive-omeprazole

Fluoxetine DRUG

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

pH positive-fluoxetine

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• age above 18 and below 60 years old

You may not qualify if:

• 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 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)
• 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

Sponsors & Collaborators

• Tehran University of Medical Sciences: lead

Study Sites (1)

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

Tehran, Tehran Province, Iran

Location

Related Publications (13)

• 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.

  PMID: 19262544 BACKGROUND

• 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.

  PMID: 12622762 BACKGROUND

• 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.

  PMID: 16042660 BACKGROUND

• 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.

  PMID: 15290657 BACKGROUND

• 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.

  PMID: 8420248 BACKGROUND

• 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.

  PMID: 16483268 BACKGROUND

• 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.

  PMID: 8078547 BACKGROUND

• 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.

  PMID: 10192608 BACKGROUND

• 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.

  PMID: 10966532 BACKGROUND

• 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.

  PMID: 16422995 BACKGROUND

• 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.

  PMID: 15651544 BACKGROUND

• 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.

  PMID: 19392864 BACKGROUND

• 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.

  PMID: 24533896 DERIVED

MeSH Terms

Conditions

Non-Erosive Reflux Disease; Heartburn

Interventions

Fluoxetine; Omeprazole

Condition Hierarchy (Ancestors)

Gastroesophageal Reflux; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Seyed Amir Mirbagheri, MD

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

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2010
• First Posted: January 4, 2011
• Study Start: August 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: March 6, 2012

Record last verified: 2012-03

Locations

IR (1)