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

February 16, 2019 updated by: Cuneyt M. Alper

Middle Ear Pressure Regulation in Health and Disease: Gas Supply, Demand and Middle-Ear Gas Balance -- Specific Aim 1

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Middle Ear Physiology Laboratory, University of PIttsburgh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: 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
Other: 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
trans-middle-ear mucosal gas exchange constants
Time Frame: Visits 2-7, approximately 2 days between visits
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cuneyt M. Alper

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Deafness and Other Communication Disorders (NIDCD)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Cuneyt M Alper, MD, University of Pittsburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 13, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 24, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 19, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 8, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 15, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 19, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 19, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 16, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2019

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PRO13050158
  • P50DC007667 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Middle Ear Gas Exchange

Clinical Trials on 6%CO2, 25%O2, balance N2

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings