A Clinical Trial of Proton Pump Inhibitors to Treat Children With Chronic Otitis Media With Effusion

This study is being done to see if reflux of stomach fluid might be a cause of chronic fluid in the ears. Our hypothesis is that treatment with an anti-reflux medication (lansoprazole) will increase the rate of resolution of chronic middle ear fluid in children.

Study Overview

• Status: Completed
• Conditions: Otitis Media With Effusion
• Intervention / Treatment: Drug: lansoprazole; Drug: placebo

Detailed Description

This study is being done to see if reflux of stomach fluid might be a cause of fluid in the ears. Earlier studies have found pepsin or pepsinogen, a component of stomach fluid, in the middle ear fluid of many children with chronic middle ear fluid. Anti-reflux medicines called proton pump inhibitors (PPI) reduce the acidity of the contents of the stomach and the activity of pepsin or pepsinogen. We are studying the effectiveness of a PPI called lansoprazole (Prevacid™) in reducing fluid in the ears. If lansoprazole is able to reduce the fluid in the middle ear, this tells us that the reflux of gastric acid into the esophagus and into the ear canal may be causing middle ear fluid.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• History of chronic otitis media with effusion meeting clinical indications for tympanostomy tubes placement, defined as the presence of middle ear fluid on physical exam for at least 3 months, in at least one ear.

Exclusion Criteria:

• Past medical history or concurrent conditions known to increase the incidence of either recurrent otitis media or otitis media with effusion or gastroesophageal reflux disease, including cleft palate, neurological delay, cerebral palsy, Down syndrome, velocardiofacial syndrome, and primary ciliary dyskinesia.
• Children with structural abnormalities of the tympanic membranes, such as cholesteatoma, deep retraction pockets, and atelectasis of the tympanic membrane. These abnormalities would require placement of tympanostomy tubes in standard clinical practice.
• Children weighing less than 10 kilograms, due to the lower weight limit for standard Prevacid™ dosing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lansoprazole (Prevacid); Prevacid SoluTab (15 or 30 mg tab) once daily for 2 months	Drug: lansoprazole; Prevacid SoluTab 15 mg daily by mouth for 2 months (patients weighing 10-30 kg),or Prevacid SoluTab 30 mg daily by mouth for 2 months (patients weighing >30 kg) is the experimental arm. Placebo Solutabs will be given in the same dosage, frequency, and duration for the placebo arm.; Other Names: Prevacid SoluTab
Placebo Comparator: Placebo; Placebo SoluTab once daily for 2 months	Drug: placebo; Placebo Solutab in 15 and 30 mg dosages.; Other Names: Placebo Solutab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absence of Middle Ear Fluid by Pneumatic Otoscopy, Right Ear	2 months
Absence of Middle Ear Fluid by Pneumatic Otoscopy, LeftEar	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acoustic Reflectometry: Level of Risk as Defined by Manufacturer	Spectral gradient acoustic reflectometry is a noninvasive, non-audible acoustic wave used to help detect middle ear fluid. The manufacturer recommends interpretation of the angle result as: <49°, high risk of middle ear effusion (level 5); 49-59°, moderate-high risk (level 4); 60-69°, moderate risk (level 3); 70-95°, low-moderate risk (level 2) and >95°, low risk (level 1).	2 months
Number of Participants With Normal Type A Tympanometry	Tympanometry of both ears, coded by Jerger classification (Type A, normal; type B, flat; Type C; negative pressure). This is a standard test of middle ear status as performed by audiologists. Please refer to the reference for more information: Kileny & Zwolan, Diagnostic Audiology, chapter 133, Cummings Otolaryngology-Head and Neck Surgery, Elsevier/Saunders, 2015.	2 months
Number of Participants With at Least 1 Symptoms of Reflux in the Past Week, Assessed by the Reflux Symptom Questionnaire	Questions regarding reflux symptoms, created and evaluated by Nelson et al, Prevalence of symptoms of gastroesophageal reflux during childhood: a pediatric practice-based survey, Arch Pediatr Adolesc Med 2000;154;150-154. This study used the GER3-9P version for children aged 3-9 years. Results are reported as number reporting at least one specific symptom in the past week, maximum 7 symptoms.	2 months

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: TAP Pharmaceutical Products Inc.; Doris Duke Charitable Foundation
• Investigators: Principal Investigator: Judith EC Lieu, MD, Washington University School of Medicine

Publications and helpful links

General Publications

• Lieu JE, Muthappan PG, Uppaluri R. Association of reflux with otitis media in children. Otolaryngol Head Neck Surg. 2005 Sep;133(3):357-61. doi: 10.1016/j.otohns.2005.05.654.
• Tasker A, Dettmar PW, Panetti M, Koufman JA, P Birchall J, Pearson JP. Is gastric reflux a cause of otitis media with effusion in children? Laryngoscope. 2002 Nov;112(11):1930-4. doi: 10.1097/00005537-200211000-00004.
• Abd El-Fattah AM, Abdul Maksoud GA, Ramadan AS, Abdalla AF, Abdel Aziz MM. Pepsin assay: a marker for reflux in pediatric glue ear. Otolaryngol Head Neck Surg. 2007 Mar;136(3):464-70. doi: 10.1016/j.otohns.2006.08.030.
• Sone M, Yamamuro Y, Hayashi H, Yanagi E, Niwa Y, Nakashima T. Prediction of gastroesophageal reflux in otitis media with effusion in adults. Acta Otolaryngol. 2007 May;127(5):470-3. doi: 10.1080/00016480600868406.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: October 17, 2007
• First Submitted That Met QC Criteria: October 17, 2007
• First Posted (Estimate): October 18, 2007

Study Record Updates

• Last Update Posted (Actual): June 1, 2018
• Last Update Submitted That Met QC Criteria: May 29, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: proton pump inhibitor; otitis media with effusion; ear infection; gastroesophageal reflux
• Additional Relevant MeSH Terms: Otorhinolaryngologic Diseases; Ear Diseases; Otitis; Otitis Media; Otitis Media with Effusion; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Dexlansoprazole; Lansoprazole
• Other Study ID Numbers: HRPO# 07-0762