Middle-ear FunctionEarly Phase 1NCT01925495
Gas Supply, Demand and Middle Ear Gas Balance: Specific Aim 3
A Early Phase 1 study testing varied middle-ear pressure, varied middle-ear gas composition and varied ear-canal pressure in people with Middle-ear Function, run by Cuneyt M. Alper at 1 site in United States.
Trial summary
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. 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 Function
- What is being tested?
- varied middle-ear pressure, varied middle-ear gas composition and varied ear-canal pressure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Dec 2016to 17 Jan 2019
- Phase
- Early 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, inclusive
- No history of significant ME disease
- No history of past ME surgeries
- 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
- Have drainage through the tympanostomy tube at the time of testing
- Taking any prescription drug with the exception of those for birth control that would interfere with study per study MD
- 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
- Pregnant or nursing
- Temporary exclusion: expected need for seasonal allergy med during study
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 3
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 3 experiments done on 5 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.
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. 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. Custom ear plugs will be made for use in Visits 2-6. The protocol includes 1 screening visit and 3 experiments requiring 5 experimental sessions of approximately 3-5 hours duration each done at a minimum interval of 2 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 3-5), the ME will be washed with physiologic, hypercarbic, 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 6), 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 7+) 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.
- Conditions
- Middle-ear Function
- Being tested
- varied middle-ear pressure, varied middle-ear gas composition, varied ear-canal pressure
- Keywords
- otitis media, middle ear, feedback pathways, middle-ear pressure
- Medical subject headings
- Otitis Media
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
varied middle-ear pressureOther
varied middle-ear gas compositionDrug
varied ear-canal pressureOther
| Study group | Role | What they receive |
|---|---|---|
| healthy adults | Experimental | Experiment 1 -- variation of ear-canal pressure; Experiment 2 -- varied middle-ear gas compositions; Experiment 3 -- variation of middle-ear pressure Receives: Other: varied middle-ear pressure; Drug: varied middle-ear gas composition; Other: varied ear-canal pressure |
What is being measured
The primary outcome is the main question the study is designed to answer.
EMG activity
integrated EMG activity of tensor veli palatini muscle in response to changes in ear canal pressure and middle-ear pressure
Measured: 2 visits (Visits 2 and 6), approximately 3 weeks apart
Secondary outcomes (1)
eustachian tube resistance
change in eustachian tube resistance in response to changes in middle ear gas composition
Measured: 3 visits, minimum 2 days apart
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 start2 Dec 2016
- Primary completion12 Nov 2018
- Study completion17 Jan 2019
Why it stopped: slow recruitment and adverse events
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Middle-ear FunctionStudies 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 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
- NCT01925495
- Sponsor's protocol ID
- PRO13050328
- Other IDs
- P50DC007667
- Status last verified
- May 2019
- First submitted
- 13 Aug 2013
- Last updated
- 17 May 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 17 May 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 3
- ClinicalTrials.gov ID
- NCT01925495
- Acronym / sponsor ID
- PRO13050328
- Conditions
- Middle-ear Function
- Keywords
- otitis media, middle ear, feedback pathways, middle-ear pressure
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow recruitment and adverse events
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Cuneyt M. AlperUniversity, hospital or other
- Collaborators
- National Institute on Deafness and Other Communication Disorders (NIDCD)
- Study start
- 2 Dec 2016 (actual)
- Primary completion
- 12 Nov 2018 (actual)
- Study completion
- 17 Jan 2019 (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 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 3 experiments done on 5 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.
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. Custom ear plugs will be made for use in Visits 2-6. The protocol includes 1 screening visit and 3 experiments requiring 5 experimental sessions of approximately 3-5 hours duration each done at a minimum interval of 2 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 3-5), the ME will be washed with physiologic, hypercarbic, 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 6), 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 7+) 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| healthy adults | Experimental | Other: varied middle-ear pressure, Drug: varied middle-ear gas composition, Other: varied ear-canal pressureExperiment 1 -- variation of ear-canal pressure; Experiment 2 -- varied middle-ear gas compositions; Experiment 3 -- variation of middle-ear pressure |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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 that would interfere with study per study MD
- 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
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 |
|---|---|---|
| varied middle-ear pressure | Other | healthy adults |
| varied middle-ear gas composition | Drug | healthy adults |
| varied ear-canal pressure | Other | healthy adults |
Primary outcome
EMG activity
Time frame: 2 visits (Visits 2 and 6), approximately 3 weeks apart
integrated EMG activity of tensor veli palatini muscle in response to changes in ear canal pressure and middle-ear pressure
1 secondary outcome
eustachian tube resistance
Time frame: 3 visits, minimum 2 days apart
Results and safety
The study was stopped early (reason given: slow recruitment and adverse events). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 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 Early Phase 1 study testing varied middle-ear pressure, varied middle-ear gas composition and varied ear-canal pressure in people with Middle-ear Function, 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 4 inclusion and 8 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: stopped early, as of the sponsor's last update on 17 May 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 was stopped early (reason given: slow recruitment and adverse events). Results are not available in the source record.
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?
EMG activity (time frame: 2 visits (Visits 2 and 6), approximately 3 weeks apart). 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 17 May 2019; AzTrials last refreshed its copy on 6 Nov 2026.