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

NCT01925482 | Completed Phase 1 FDA Drug

• 2 other identifiers: PRO13050158P50DC007667
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Middle Ear Gas Exchange

Keywords

middle ear; otitis; gas exchange

Outcome Measures

Primary Outcomes (1)

• trans-middle-ear mucosal gas exchange constants

  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)

  Visits 2-7, approximately 2 days between visits

Study Arms (2)

Group 1 -- no history of otitis media

OTHER

no history of otitis media

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

Group 2 --patent tympanostomy tube

OTHER

at least 1 patent tympanostomy tube

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

Interventions

6%CO2, 25%O2, balance N2 DRUG

exposure of middle ear to gas

Group 1 -- no history of otitis media; Group 2 --patent tympanostomy tube

6% CO2, 0%O2, balance N2 DRUG

exposure of middle ear to gas

Group 1 -- no history of otitis media; Group 2 --patent tympanostomy tube

20%CO2, 6%O2, balance N2 DRUG

exposure of middle ear to gas

Group 1 -- no history of otitis media; Group 2 --patent tympanostomy tube

0%CO2, 6%O2, balance N2 DRUG

exposure of middle ear to gas

Group 1 -- no history of otitis media; Group 2 --patent tympanostomy tube

6% CO2, 6%O2, balance N2 DRUG

exposure of middle ear to gas

Group 1 -- no history of otitis media; Group 2 --patent tympanostomy tube

6%CO2, 6%O2, 0%N2, balance argon DRUG

exposure of middle ear to gas

Group 1 -- no history of otitis media; Group 2 --patent tympanostomy tube

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Otherwise healthy adults aged 18 to 50 years
• No history of significant ME disease; intact tympanic membrane (Group 1 only)
• Functional tympanostomy tube or chronic perforation after tube extruded; tube placed for middle-ear effusion/Eustachian tube dysfunction (Group 2)
• No history of past ME surgeries other than ventilation tubes (Group 2),
• Able to comprehend study risks and provide written Informed Consent

You may not qualify if:

• 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)

Sponsors & Collaborators

• Cuneyt M. Alper: lead
• National Institute on Deafness and Other Communication Disorders (NIDCD): collaborator

Study Sites (1)

Middle Ear Physiology Laboratory, University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Otitis

Condition Hierarchy (Ancestors)

Ear Diseases; Otorhinolaryngologic Diseases

Study Officials

• Cuneyt M Alper, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Otolaryngology

Study Record Dates

• First Submitted: August 8, 2013
• First Posted: August 19, 2013
• Study Start: May 13, 2014
• Primary Completion: April 24, 2015
• Study Completion: May 19, 2015
• Last Updated: February 19, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)