Gas Supply, Demand and Middle Ear Gas Balance: Specific Aim 3

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01925495
Recruitment Status : Recruiting
First Posted : August 19, 2013
Last Update Posted : February 8, 2018
National Institute on Deafness and Other Communication Disorders (NIDCD)
Information provided by (Responsible Party):
Cuneyt M. Alper, University of Pittsburgh

Brief Summary:

This is a study to determine if there are reflexes that detect changes in eardrum position or in the pressure of middle-ear gases and respond with changes in the ease by which the Eustachian tube is opened. The Eustachian tube is the normal tube that connects the middle ear to the nose. It is usually closed, but can be opened by contraction of 2 small muscles that surround the tube. If the Eustachian tube does not open frequently enough, the pressure in the middle ear will decrease, the eardrum will be pulled in toward the middle ear causing a hearing loss, and fluid will accumulate in the middle ear to try and stabilize its pressure. There is some evidence that the changes in eardrum position and middle-ear pressure when the Eustachian tube does not open frequently enough can be detected by the brain that, in turn, sends signals to the Eustachian tube and its muscles to make Eustachian tube opening easier. In this study, we will test this possibility.

Specifically, in 3 experiments done on 5 different days, we will move the eardrum in and out, apply different pressures to the middle ear, or change the composition of the gases in the middle ear while we measure how difficult it is to open the Eustachian tube by increasing middle-ear pressure or by measuring the "readiness" of the Eustachian tube muscles to contract and open the tube.

Condition or disease Intervention/treatment Phase
Middle-ear Function Other: varied middle-ear pressure Drug: varied middle-ear gas composition Other: varied ear-canal pressure Not Applicable

Detailed Description:

Adequate middle ear (ME) pressure-regulation, defined as the maintenance of a total ME pressure at approximately ambient levels, is required for normal hearing and to preserve ME health. The mechanism of ME pressure-regulation consists of two distinct components that affect total ME gas pressure: the bolus, total gradient driven exchange of gases between the ME and nasopharynx during active, transient Eustachian tube (ET) openings and the passive, partial-pressure gradient driven diffusive exchange of gases between the ME cavity and adjacent compartments. A large number of past studies have described the basic physiology of gas transfers through the ET in humans, but few have explored the possibility that physiological feedback mechanisms could modulate ET functional efficiency. However, there is an anatomic foundation to support feedback modulation of ET function and the results for some experiments in animals lend credibility to that possibility. Theoretically, the sensory components of possible feedback pathways could consist of stretch sensors in the tympanic membrane (TM; detecting position) and tensor tympani muscle (detecting tension) and/or chemo- (detecting gas pressures)/ baro- (detecting total pressure) receptors in the ME mucosa and effector components consisting of resting Tensor Veli Palatini muscle (mTVP) tonus and/or the extant ET periluminal pressure.

In this study, we explore 3 hypothesized stimulus-effector pairings in 10 otherwise healthy adult subjects with no history of significant ME disease and normal audiologic testing. Custom ear plugs will be made for use in Visits 2-6. The protocol includes 1 screening visit and 3 experiments requiring 5 experimental sessions of approximately 3-5 hours duration each done at a minimum interval of 2 days. Briefly, in Experiment 1 (Visit 2), ear canal pressure will be varied to change the position of the TM while simultaneously monitoring mTVP tonus by electromyography (EMG). Then, a unilateral ventilation tube (VT) inserted into the TM to allow access to the ME cavity. For Experiment 2, (Visits 3-5), the ME will be washed with physiologic, hypercarbic, and hyperoxic gas compositions (reference ME normal) while monitoring the ET periluminal tissue pressures measured as the ET resistance to gas flow. For Experiment 3 (Visit 6), total ME pressure will be varied while monitoring mTVP tonus by EMG. At the completion of Experiment 3, the VT will be removed and, then, the subjects will be followed weekly (Visits 7+) until documented healing of the TM at which time a standard audiologic assessment will be done. If the hypotheses are supported, selected activation of the feedback mechanisms would improve ET function and could be exploited as one component of a treatment protocol to improve ME pressure-regulation.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Middle Ear Pressure Regulation in Health and Disease/Gas Supply, Demand and Middle Ear Gas Balance: Specific Aim 3
Study Start Date : November 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Arm Intervention/treatment
Experimental: healthy adults
Experiment 1 -- variation of ear-canal pressure; Experiment 2 -- varied middle-ear gas compositions; Experiment 3 -- variation of middle-ear pressure
Other: varied middle-ear pressure
Drug: varied middle-ear gas composition
Other: varied ear-canal pressure

Primary Outcome Measures :
  1. EMG activity [ Time Frame: 2 visits (Visits 2 and 6), approximately 3 weeks apart ]
    integrated EMG activity of tensor veli palatini muscle in response to changes in ear canal pressure and middle-ear pressure

Secondary Outcome Measures :
  1. eustachian tube resistance [ Time Frame: 3 visits, minimum 2 days apart ]
    change in eustachian tube resistance in response to changes in middle ear gas composition

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Otherwise healthy adults aged 18 to 50 years, inclusive
  • No history of significant ME disease
  • No history of past ME surgeries
  • Able to comprehend study risks and provide written Informed Consent

Exclusion Criteria:

  • Have any chronic health problem
  • Have ME fluid or otitis media (OM)at the time of presentation
  • Have drainage through the tympanostomy tube at the time of testing
  • Taking any prescription drug with the exception of those for birth control that would interfere with study per study MD
  • Have a known or suspected allergy/adverse reaction to any of the study drugs use to prepare the tympanic membrane for ventilation tube insertion or the nasopharynx for EMG needle insertion
  • Have a hearing threshold >15 dB or a >10 dB air-bone gap at any of the speech frequencies
  • Pregnant or nursing
  • Temporary exclusion: expected need for seasonal allergy med during study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01925495

Contact: Julianne Banks, BS 412-692-3595

United States, Pennsylvania
Middle Ear Physiology Laboratory, University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Julie Banks    412-692-3595      
Principal Investigator: Cuneyt M Alper, MD         
Sub-Investigator: Ellen M Mandel, MD         
Sub-Investigator: Douglas Swarts, PhD         
Sub-Investigator: Miriam S Teixeira, MD, PhD         
Sub-Investigator: Margaretha L Casselbrant, MD, PhD         
Sub-Investigator: Beverly C Richert, PhD, RN, CRNP         
Sponsors and Collaborators
Cuneyt M. Alper
National Institute on Deafness and Other Communication Disorders (NIDCD)
Principal Investigator: Cuneyt M Alper, MD University of Pittsburgh

Responsible Party: Cuneyt M. Alper, Professor, Otolaryngology, University of Pittsburgh Identifier: NCT01925495     History of Changes
Other Study ID Numbers: PRO13050328
P50DC007667 ( U.S. NIH Grant/Contract )
First Posted: August 19, 2013    Key Record Dates
Last Update Posted: February 8, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Cuneyt M. Alper, University of Pittsburgh:
otitis media
middle ear
feedback pathways
middle-ear pressure