Middle Ear Gas ExchangePhase 1NCT01925482
Trans-Middle-Ear Mucosal Gas Exchange Project 1, Specific Aim 1
A Phase 1 study testing 6%CO2, 25%O2, balance N2, 6% CO2, 0%O2, balance N2 and 20%CO2, 6%O2, balance N2 in people with Middle Ear Gas Exchange, run by Cuneyt M. Alper at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Middle Ear Gas Exchange
- What is being tested?
- 6%CO2, 25%O2, balance N2, 6% CO2, 0%O2, balance N2 and 20%CO2, 6%O2, balance N2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 13 May 2014to 19 May 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Middle Ear Physiology Laboratory, University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: 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.
Read the 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.
- Conditions
- Middle Ear Gas Exchange
- Being tested
- 6%CO2, 25%O2, balance N2, 6% CO2, 0%O2, balance N2, 20%CO2, 6%O2, balance N2, 0%CO2, 6%O2, balance N2, 6% CO2, 6%O2, balance N2
- Keywords
- middle ear, otitis, gas exchange
- Medical subject headings
- Otitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
6%CO2, 25%O2, balance N2Drug
exposure of middle ear to gas
6% CO2, 0%O2, balance N2Drug
exposure of middle ear to gas
20%CO2, 6%O2, balance N2Drug
exposure of middle ear to gas
0%CO2, 6%O2, balance N2Drug
exposure of middle ear to gas
6% CO2, 6%O2, balance N2Drug
exposure of middle ear to gas
6%CO2, 6%O2, 0%N2, balance argonDrug
exposure of middle ear to gas
| Study group | Role | What they receive |
|---|---|---|
| Group 1 -- no history of otitis media | Other | no history of otitis media Receives: 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 Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Visits 2-7, approximately 2 days between visits
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2013 (estimated)
- Study start13 May 2014
- Primary completion24 Apr 2015
- Study completion19 May 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Middle Ear Gas ExchangeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cuneyt M. Alper
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Deafness and Other Communication Disorders (NIDCD)
- Responsible party
- Sponsor-investigator, Cuneyt M. Alper, University of Pittsburgh
- Investigators
- Cuneyt M Alper, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01925482
- Sponsor's protocol ID
- PRO13050158
- Other IDs
- P50DC007667
- Status last verified
- Feb 2019
- First submitted
- 8 Aug 2013
- Last updated
- 19 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Middle Ear Pressure Regulation in Health and Disease: Gas Supply, Demand and Middle-Ear Gas Balance -- Specific Aim 1
- ClinicalTrials.gov ID
- NCT01925482
- Acronym / sponsor ID
- PRO13050158
- Conditions
- Middle Ear Gas Exchange
- Keywords
- middle ear, otitis, gas exchange
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Cuneyt M. AlperUniversity, hospital or other
- Collaborators
- National Institute on Deafness and Other Communication Disorders (NIDCD)
- Study start
- 13 May 2014 (actual)
- Primary completion
- 24 Apr 2015 (actual)
- Study completion
- 19 May 2015 (actual)
- First posted
- 19 Aug 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 -- no history of otitis media | Other | 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 argonno history of otitis media |
| Group 2 --patent tympanostomy tube | Other | 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 argonat least 1 patent tympanostomy tube |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 6%CO2, 25%O2, balance N2exposure of middle ear to gas | Drug | Group 1 -- no history of otitis media, Group 2 --patent tympanostomy tube |
| 6% CO2, 0%O2, balance N2exposure of middle ear to gas | Drug | Group 1 -- no history of otitis media, Group 2 --patent tympanostomy tube |
| 20%CO2, 6%O2, balance N2exposure of middle ear to gas | Drug | Group 1 -- no history of otitis media, Group 2 --patent tympanostomy tube |
| 0%CO2, 6%O2, balance N2exposure of middle ear to gas | Drug | Group 1 -- no history of otitis media, Group 2 --patent tympanostomy tube |
| 6% CO2, 6%O2, balance N2exposure of middle ear to gas | Drug | Group 1 -- no history of otitis media, Group 2 --patent tympanostomy tube |
| 6%CO2, 6%O2, 0%N2, balance argonexposure of middle ear to gas | Drug | Group 1 -- no history of otitis media, Group 2 --patent tympanostomy tube |
Primary outcome
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2019.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cuneyt M Alper, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 6%CO2, 25%O2, balance N2, 6% CO2, 0%O2, balance N2 and 20%CO2, 6%O2, balance N2 in people with Middle Ear Gas Exchange, run by Cuneyt M. Alper at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
trans-middle-ear mucosal gas exchange constants (time frame: Visits 2-7, approximately 2 days between visits). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2019.