Clinical trial NCT01082029: Study of Anti-reflux Medication as a Potential Treatment for Glue Ear in Children
Official title: Role of Empiric Anti-reflux Therapy in Pediatric Otitis Media With Effusion - a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Otitis Media With Effusion
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: McMaster University
First posted: 2010-03-05
Enrollment: 65
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The accumulation of fluid behind the ear drum without any acute inflammation is known as otitis media with effusion (OME). It is the most common cause of acquired hearing loss during childhood. Long-term complications of OME include linguistic, developmental, and social development delays due to hearing loss.

The cause of OME is not known; however, low grade infection of the middle ear, poor function of the eustachian tube between the ear and the throat, and adenoid hypertrophy have all been suggested as possible etiologies. Recent detection of the stomach enzyme pepsin in middle ear fluid has led some to propose that OME is related to the reflux of stomach contents into the ear, via the eustachian tube.

The purpose of the investigators study is to determine whether anti-reflux medication may have a positive impact by clearing the accumulation of fluid in the middle ear with the aim of preventing or reducing hearing loss in children diagnosed with OME. Empiric anti-reflux therapy with proton pump inhibitor (PPI) medication is safe, proven and cost-effective. It is used widely as a diagnostic and treatment strategy in the presence of the signs and symptoms of gastroesophageal reflux disease (GERD). The signs and symptoms of GERD include heartburn, recurrent vomiting or regurgitation, acid taste in mouth, throat irritation, voice problems, heartburn, difficult or painful swallowing, asthma and recurrent pneumonia.

This pilot study will be a double-blinded, randomized, placebo-controlled trial that will compare resolution rates for OME in children treated with lansoprazole or placebo for three months. At the end of the study, those patients who have persistent middle ear effusions will be brought to the operating room and have the fluid aspirated and sent for analysis for pepsin.

Detailed description: Otitis media with effusion (OME) is a condition characterized by the accumulation of non-purulent fluid in the middle ear space, in the absence of acute inflammation. OME is diagnosed 2.2 million times annually (U.S. Department of Health \& Human Services, 2000). It is a condition in which more then 50% of children will experience in their first year of life (National Institutes of Health, 1993). Although many episodes resolve spontaneously, 30% to 40% persist, and 5% to 10% of episodes last 1 year or longer (Yoshinaga-Itano, 1995). It is particularly more common among children between the ages of one and three years and in seasons where the prevalence of upper respiratory tract infections is high; with an incidence of 10% to 30%. It occurs frequently even up to the age of seven, with a prevalence of 3% to 8%(Fiellau et al, 1997; Fiellau et al, 1983; Lous et al, 1981; Teele et al, 1989).

OME is the most common cause of acquired hearing loss in childhood. Long-term hearing complications from OME are associated with linguistic, developmental, and social consequences; especially if the OME is bilateral and of long duration (Fiellau et al, 1983; Golz et al, 1998; Grace et al, 1990; Lous et al, 1995). The etiology of OME is uncertain; however, low-grade infection, poor eustachian tube function, formation of biofilms, and adenoidal infection or hypertrophy have all been suggested as possible etiologies (Faden et al, 1998; Hall-Stoodley et al, 2006).

Recently, there has been good scientific evidence to suggest that OME is a supraesophageal manifestation of gastroesophageal reflux disease (GERD), and more specifically laryngo-pharyngeal reflux (LPR). Tasker et al (2002) investigated the potential role of gastric reflux in the development of OME in children who underwent myringotomy. Of 65 tested effusion samples, 59 (91%) effusions gave a positive result. The concentrations of pepsin/pepsinogen were roughly estimated to be about 1000 times higher than those found in the serum obtained from a number of controls. They speculated that pepsin found in middle ear effusion (MEE) was most probably due to micro-aspiration of gastric contents passing through the eustachian tube (ET) and reaching the middle ear. Lieu et al (2005) performed a pilot study where they replicated the finding of pepsin/pepsinogen in 17 of 36 (77%) middle ear fluid aspirates, obtained from 22 children who underwent tympanostomy tube placement for chronic or recurrent otitis media (OM).

Based on our literature review, we believe there is sufficient scientific evidence to support the empiric treatment of suspected GERD and LPR in patients with OME. Empiric anti-reflux therapy is a safe, proven, cost-effective diagnostic and treatment strategy used widely in the presence of other signs and symptoms of suspected GERD. This pilot study will be a double-blinded, randomized control trial. It will compare hearing outcomes for children with OME being treated with lansoprazole versus placebo for three months. We believe there is sufficient evidence to support the use of this strategy in patients with suspected GERD and LPR who present with OME.

Eligibility criteria: Inclusion Criteria:

* Children between the ages of 1 and 17 years referred to the McMaster Otolaryngology Clinic.
* Presence of bilateral OME for at least 3 months based on:

  * Clinical history: patient may present with decrease in hearing, aural fullness and/or ear pressure, balance problems, ear tugging/rubbing, they typically do not have otalgia or fever.
  * Pneumatic otoscopy: observations suggestive of OME include presence of a dull tympanic membrane with presence of non purulent effusion (serous or mucoid), presence of a level of effusion, decrease or non motility of the tympanic membrane, retraction of the tympanic membrane.
  * Tympanometry: type B or type C tympanogram with normal air volume of the external auditory canal.
  * Pure tone audiometry: conductive hearing loss that typically varies from slight to moderate.

Exclusion Criteria:

* Presence of acute otitis media as determined by history and physical examination:

  * History of rapid acute onset of significant otalgia, decrease in hearing, fever, irritability.
  * Pneumatic otoscopy revealing purulent effusion, yellowness and/or redness with hypervascularity of the tympanic membrane, bulging of tympanic membrane with decrease of normal landmarks.
* Presence of craniofacial abnormalities
* Previous middle ear surgery (excluding myringotomy and tube)
* Allergic reactions to lansoprazole, and any other adverse drug interactions to lansoprazole.

Primary outcomes:
measure: Collect the required data for sample size calculation
timeFrame: Following the recruitment of 100 patients (~1 year)
Secondary outcomes:
measure: Resolution of Otitis Media with Effusion
timeFrame: At presentation and at 1 month, 2months and 3 months post initiation of treatment
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Mcmaster University Medical Centre 3V1 Clinic
state: Ontario
Study officials:
affiliation: McMaster University
name: Dr. Diane Reid, MD FRCSC
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: Dr. Gavin Rukholm, MD
role: PRINCIPAL_INVESTIGATOR
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