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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by University of Pittsburgh
Sponsor:
Collaborator:
Information provided by (Responsible Party):
William J. Doyle, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01925495
First received: August 13, 2013
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

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 7 experiments done on 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 Intervention
Middle-ear Function
Other: varied middle-ear pressure
Drug: varied middle-ear gas composition
Other: varied ear-canal pressure

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • EMG activity [ Time Frame: 2 visits (Visits 2 and 8), approximately 3 weeks apart ] [ Designated as safety issue: No ]
    integrated EMG activity of tensor veli palatini muscle in response to changes in ear canal pressure and middle-ear pressure


Secondary Outcome Measures:
  • eustachian tube resistance [ Time Frame: 6 visits, approximately 2-3 days apart ] [ Designated as safety issue: No ]
    change in eustachian tube resistance in response to changes in middle ear gas composition


Estimated Enrollment: 10
Study Start Date: July 2014
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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. A custom ear plug will be made for use in Visits 3-7. The protocol includes 1 screening visit and 3 experiments requiring 7 experimental sessions of approximately 3-4 hours duration each done at a minimum interval of 3 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 3-7), the ME will be washed with physiologic, hypocarbic, hypercarbic, hypooxic 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 8), 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 9+) 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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01925495

Contacts
Contact: Julianne Banks, BS 412-692-3595
Contact: Jenna El-Wagaa 412-692-3595

Locations
United States, Pennsylvania
Middle Ear Physiology Laboratory, University of Pittsburgh Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15213
Sub-Investigator: Cuneyt M Alper, MD         
Principal Investigator: William J Doyle, PhD         
Sub-Investigator: Ellen M Mandel, MD         
Sub-Investigator: Douglas Swarts, PhD         
Sub-Investigator: Miriam S Teixeira, MD, PhD         
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: William J Doyle, PhD University of Pittsburgh
  More Information

No publications provided

Responsible Party: William J. Doyle, Professor of Otolaryngology, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01925495     History of Changes
Other Study ID Numbers: PRO13050328, P50DC007667
Study First Received: August 13, 2013
Last Updated: February 18, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
otitis media
middle ear
feedback pathways
middle-ear pressure

ClinicalTrials.gov processed this record on September 18, 2014