Trans-Middle-Ear Mucosal Gas Exchange Project 1, Specific Aim 1

This study is currently recruiting participants. (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:
NCT01925482
First received: August 8, 2013
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

This study will measure the speed at which gases move between the middle-ear air-space and the blood flowing through the middle-ear lining. The middle ear is a rigid biological gas pocket located behind the eardrum and is filled with the same gases as in air, primarily oxygen (O), nitrogen (N) and carbon dioxide (CO2), but in different proportions. The middle ear is lined by a thin layer of cells overlying tissues that surround blood vessels. The blood that flows through the middle-ear lining also contains these same gases but at different proportions from both the atmosphere (room air) and middle ear. Because of the differences in the proportions of these gases, each gas tends to flow between the middle ear and blood trying to make the proportions of gases in those compartments the same. This flow of gases to and from the middle ear changes the middle-ear pressure. If the middle-ear pressure decreases much below the air pressure of the atmosphere, the ability to hear sounds is impaired and fluid can build up in the middle ear. It is expected that each different gas will move between the middle ear and blood at a different speed, but it is not known what those speeds are for any of the gases. It is also expected that those speeds will be different for ears that have had middle-ear disease and those that have not. In this study, we will measure the speed of nitrogen, oxygen and carbon dioxide exchanges in both directions between the middle ear and blood. To do this, the gas mixture in the middle ear will be changed so that there is movement of only one gas for each experiment and then measure the change in the amount of the gas in the middle ear. This can be done using a special instrument called a mass spectrometer if there is an open, working tympanostomy (ventilation) tube, a small plastic tube, in the eardrum. For all participants in this study, we will conduct 6 experiments lasting about 2 hours each to measure the speed of nitrogen, oxygen and carbon dioxide flow. Subjects with and without tympanostomy tubes will be recruited. Those without a tube will have a tube inserted in one ear for study purposes and it will be removed at the end of the study; these subjects will be followed weekly until the hole in the eardrum (where the tube was) is closed.


Condition Intervention
Middle Ear Gas Exchange
Drug: 6%CO2, 25%O2, balance N2
Drug: 6% CO2, 0%O2, balance N2
Drug: 20%CO2, 6%O2, balance N2
Drug: 0%CO2, 6%O2, balance N2
Drug: 6% CO2, 6%O2, balance N2
Drug: 6%CO2, 6%O2, 0%N2, balance argon

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Crossover 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 1

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • trans-middle-ear mucosal gas exchange constants [ Time Frame: Visits 2-7, approximately 2 days between visits ] [ Designated as safety issue: No ]
    trans-middle-ear mucosal gas exchange constants for the 3 physiological gases and 2 exchange directions will be measured at each visit (1 intervention/visit)


Estimated Enrollment: 20
Study Start Date: September 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Group 1 -- no history of otitis media
no history of otitis media
Drug: 6%CO2, 25%O2, balance N2
exposure of middle ear to gas
Drug: 6% CO2, 0%O2, balance N2
exposure of middle ear to gas
Drug: 20%CO2, 6%O2, balance N2
exposure of middle ear to gas
Drug: 0%CO2, 6%O2, balance N2
exposure of middle ear to gas
Drug: 6% CO2, 6%O2, balance N2
exposure of middle ear to gas
Drug: 6%CO2, 6%O2, 0%N2, balance argon
exposure of middle ear to gas
Group 2 --patent tympanostomy tube
at least 1 patent tympanostomy tube
Drug: 6%CO2, 25%O2, balance N2
exposure of middle ear to gas
Drug: 6% CO2, 0%O2, balance N2
exposure of middle ear to gas
Drug: 20%CO2, 6%O2, balance N2
exposure of middle ear to gas
Drug: 0%CO2, 6%O2, balance N2
exposure of middle ear to gas
Drug: 6% CO2, 6%O2, balance N2
exposure of middle ear to gas
Drug: 6%CO2, 6%O2, 0%N2, balance argon
exposure of middle ear to gas

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 including the local blood via the ME mucosa (MEM) and environment via the tympanic membrane. The basic physiology of gas transfers through the ET is well established and a slow to negligible gas exchange across the normal and inflamed tympanic membrane has been measured for chinchillas, cats and monkeys, and confirmed by us for humans. In contrast, the characteristics of transMEM gas exchange is controversial. Mathematical modeling shows that transMEM gas exchange controls the ME pressure trajectory between ET openings and the relative rates of exchange for the different physiologic gases defines the demand placed on the ET for ME gas resupply. Here, we empirically measure the transMEM ME-to-blood and the blood-to-ME exchange constants for the physiologic gases in humans with normal and inflamed MEMs. For that purpose, a total of 20 otherwise healthy adult subjects, 10 with no significant history of ME ear disease (Group-1) and 10 with at least 1 functional ventilation tube (VT) inserted for extant ME disease (Group-2). Group-1 subjects will have VT insertion under local anesthetic in the research clinic and, for all subjects, a custom-made acrylic ear-plug will be fabricated and fitted with a sensor for measuring pressure, a syringe for adjusting system pressure and micro-tubing to allow for periodic gas sampling with composition analysis by an online mass-spectrometer. All subjects will undergo a series of six transMEM gas exchange experiments, with each experiment designed to establish a ME-to-blood or a blood-to-ME partial-pressure gradient for one of the 3 physiologic gases, N2, O2 or CO2. During each experiment, the ear-plug will be inserted into and sealed within the ear canal. The ear-plug will be attached by valves to a line leading to the mass-spectrometer and to a known composition gas source, and the system (ear-plug + ME) washed with a test gas specific to the experiment. Then, the ear-plug will be closed to the gas source, and for the 60 to 90 minute duration of the experiment, system pressure will be recorded continuously and ME gas samples will be taken at 10 minute intervals for composition analysis. The data will be transformed to estimate the transMEM conductance (exchange constant) for the test gas. On the last day of the experimental series, the Group-2 subjects will be dismissed; Group-1 subjects will have their VT removed and then be followed weekly until the tympanic membrane perforation has healed. At that time, audiometry which was performed before VT insertion will be repeated. The results will be used to complete our mathematical models of ME pressure-regulation as the ME transitions from health to disease. These empirical data will also be used to evaluate certain hypotheses related to the limitations placed on the exchange of each gas species and regarding the directional symmetry of the exchange processes.

  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
  • No history of significant ME disease (Group 1 only)
  • No history of past ME surgeries other than ventilation tubes,
  • 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 for ventilation tube insertion (Group 1 only)
  • Have drainage through the ventilation tube at the time of testing
  • Have a cold or allergic rhinitis 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 (Group 1 only)
  • Have a hearing threshold >15 dB or a >10 dB air-bone gap at any of the speech frequencies (Group 1 only)
  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: NCT01925482

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 Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Principal Investigator: William J Doyle, PhD         
Sub-Investigator: Cuneyt M Alper, MD         
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: NCT01925482     History of Changes
Other Study ID Numbers: PRO13050158, P50DC007667
Study First Received: August 8, 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:
middle ear
otitis
gas exchange

ClinicalTrials.gov processed this record on July 24, 2014