Tympanic Membrane PerforationPhase 2NCT02307916
Fibroblast Growth Factor Regeneration of Tympanic Membrane Perforations
A Phase 2 study testing FGF-2 in people with Tympanic Membrane Perforation, run by D. Bradley Welling, MD, PhD at 2 sites in United States.
Trial summary
A Phase II randomized trial will be initiated to evaluate closure of the perforated tympanic membrane as the primary measureable outcome. The goal is to determine the safety and efficacy of Fibroblast Growth Factor-2 (FGF-2) in the closure of chronic tympanic membrane perforations (TMP). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tympanic Membrane Perforation
- What is being tested?
- FGF-2
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 57 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2016to Mar 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Dry tympanic membrane perforation of greater than 3 months duration
- If female, post-menopausal or sterile, or if she is of child-bearing potential, must have a negative beta-human chorionic gonadotropin (HCG) test and must be using an adequate form of birth control such as birth control pills, birth control implants, intrauterine devices (IUDs), diaphragms or condoms.
Who cannot join
- The presence of any of the following excludes a subject from study enrollment:
- Active otitis media or chronic otorrhea from the middle ear
- Subjects receiving radiation therapy, corticosteroids, immunosuppressive agents or chemotherapy
- Subjects who, at study entry, are taking systemic antibiotics
- Subjects who are immunosuppressed
- Subjects experiencing bacterial or viral infection or who may otherwise be febrile
Show all 14Show fewer
- Life expectancy of less than 1 year
- Active alcohol or drug abuse within 6 months prior to study entry
- Significant medical condition that could prevent full participation in the procedures required for the study (See body of protocol for full list of exclusions)
- Known or suspected allergies to any components used in the study
- Subjects who have cholesteatoma mass in the tympanic cavity
- Subjects whose total perforation cannot be seen by an endoscope
- Subjects with inadequately controlled diabetes mellitus (NGSP: HbA1c 6.9% or higher)
- Subjects with a history of malignant ear canal tumors within 3 years of screening for eligibility
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts Eye and Ear
Boston, Massachusetts, 02114
Wilford Hall, Lackland Airforce Base
Lackland City, Texas, 78236
About this study
A Phase II randomized trial will be initiated to evaluate closure of the perforated tympanic membrane as the primary measureable outcome. The goal is to determine the safety and efficacy of Fibroblast Growth Factor-2 (FGF-2) in the closure of chronic tympanic membrane perforations (TMP). If FGF-2 is topically applied for the treatment of chronic TMP in humans, it is hypothesized it will be safe, tolerable and effective for use as treatment for tympanic membrane perforation. A total of 60 subjects will be recruited.
Read the detailed description
A Phase II randomized trial will be initiated to evaluate efficacy as the primary measureable outcome. Eligible and consented patients will be randomized in a 3:1 ratio to the optimal biologic dose (OBD) of FGF-2 or placebo (sterile water).
Application of the study treatment may occur at the initial Screening Visit (pending all eligibility requirements can be confirmed) or at Visit 1 and may be repeated at each follow up visit as needed for a maximum of three treatments per treatment arm. These follow up visits will occur three weeks (+/- 7 days) from the last treatment application. During these visits, the subject's tympanic membrane will be examined, photographed, and additional otologic tests will be performed. If the perforation is found to be closed during these visits, then the subject will report in 2 months (+/-7 days) for a final study visit.
If the subject's TMP has not closed after the third and final application of their assigned treatment group, then the subject will be crossed over to the other treatment group. Again, the subject may be given up to three additional treatments in this new group. The follow up visits will follow the same schedule, occurring three weeks (+/- 7 days) from the last treatment. The same otologic procedures will be performed as in the previous visits.
All subjects will report for a final study visit 2 months (+/- 7 days) after their last follow up visit when the perforation is determined to be closed or when the subject has completed the maximum number of study visits without perforation closure. The study will be completed for reporting purposes after all subjects have completed the 2 month (+/- 7 days) follow up final visit.
- Conditions
- Tympanic Membrane Perforation
- Being tested
- FGF-2, Placebo
- Keywords
- tympanic membrane perforation, ear drum, hole
- Medical subject headings
- Tympanic Membrane Perforation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FGF-2Drug
Also called FGF2, Human Fibroblast Growth Factor 2
The FGF-2 method of use comprises a pledget of gelatin foam with human fibroblast growth factor-2 (FGF-2) added to the pledget just before topical application to the tympanic membrane, and the use of Tisseel, a fibrin glue used for applications in ear surgery.
PlaceboOther
Also called Placebo comparator; sterile saline
Placebo comparator using a sterile saline solution.
| Study group | Role | What they receive |
|---|---|---|
| FGF-2 | Experimental | FGF-2 given a minimum of 1 and maximum of 3 times within, approximately, 60 days. Receives: Drug: FGF-2 |
| Placebo | Placebo comparator | Equal concentration of saline is given a minimum of 1 and maximum of 3 times within, approximately, 60 days. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Tympanic Membrane Closure Following Treatment
The efficacy of the treatment is determined by the number of patients whose tympanic membrane perforations closed after study treatments. Subjects from both treatment arms received up to three treatments before determining non-closure of the tympanic membrane.
Measured: ~60 days
Secondary outcomes (4)
Measurement of Changes in Pure-tone Averages
measured by pre- and post-treatment audiograms.
Measured: Baseline, 60 days
Measurement of Changes in Speech Discrimination Scores
Speech discrimination score is determined by having the patient listen to words through headphones and having the patient repeat the words back to the audiologist. A score of 100 percent (100%) is the best outcome, and 0 percent (0%) is the worst. Pre- and post- treatment tests are compared and analyzed.
Measured: Baseline, 60 days
Number of Treatments Required for Closure of the Tympanic Membrane Perforation
Out of the patients who healed, some healed with 1 treatment, some with 2 treatments, and some with 3 treatments.
Measured: 60 days
Number of Patients With Normal Mobility of the Eardrum as Assessed by Tympanometry
Tympanometry is an examination used to test the condition of the middle ear and the mobility of the eardrum. Any type of perforation, regardless of size, would cause the result of the tympanometry to be abnormal. We use this test to determine if the eardrum closed completely.
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2014 (estimated)
- Study startOct 2016
- Primary completionJul 2019
- Study completionMar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Tympanic Membrane PerforationStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- D. Bradley Welling, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor-investigator, D. Bradley Welling, MD, PhD, Massachusetts Eye and Ear Infirmary
- Investigators
- D. B. Welling, M.D., Ph.D, Principal investigator, Massachusetts Eye and Ear
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02307916
- Sponsor's protocol ID
- 16-043
- Status last verified
- Dec 2020
- First submitted
- 2 Dec 2014
- Last updated
- 8 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fibroblast Growth Factor Regeneration of Tympanic Membrane Perforations
- ClinicalTrials.gov ID
- NCT02307916
- Acronym / sponsor ID
- 16-043
- Conditions
- Tympanic Membrane Perforation
- Keywords
- tympanic membrane perforation, ear drum, hole
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- D. Bradley Welling, MD, PhDUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- Oct 2016
- Primary completion
- Jul 2019 (actual)
- Study completion
- Mar 2020 (actual)
- First posted
- 4 Dec 2014 (estimated)
- Results
- Posted 11 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase II randomized trial will be initiated to evaluate closure of the perforated tympanic membrane as the primary measureable outcome. The goal is to determine the safety and efficacy of Fibroblast Growth Factor-2 (FGF-2) in the closure of chronic tympanic membrane perforations (TMP). If FGF-2 is topically applied for the treatment of chronic TMP in humans, it is hypothesized it will be safe, tolerable and effective for use as treatment for tympanic membrane perforation. A total of 60 subjects will be recruited.
Detailed description
A Phase II randomized trial will be initiated to evaluate efficacy as the primary measureable outcome. Eligible and consented patients will be randomized in a 3:1 ratio to the optimal biologic dose (OBD) of FGF-2 or placebo (sterile water).
Application of the study treatment may occur at the initial Screening Visit (pending all eligibility requirements can be confirmed) or at Visit 1 and may be repeated at each follow up visit as needed for a maximum of three treatments per treatment arm. These follow up visits will occur three weeks (+/- 7 days) from the last treatment application. During these visits, the subject's tympanic membrane will be examined, photographed, and additional otologic tests will be performed. If the perforation is found to be closed during these visits, then the subject will report in 2 months (+/-7 days) for a final study visit.
If the subject's TMP has not closed after the third and final application of their assigned treatment group, then the subject will be crossed over to the other treatment group. Again, the subject may be given up to three additional treatments in this new group. The follow up visits will follow the same schedule, occurring three weeks (+/- 7 days) from the last treatment. The same otologic procedures will be performed as in the previous visits.
All subjects will report for a final study visit 2 months (+/- 7 days) after their last follow up visit when the perforation is determined to be closed or when the subject has completed the maximum number of study visits without perforation closure. The study will be completed for reporting purposes after all subjects have completed the 2 month (+/- 7 days) follow up final visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FGF-2 | Experimental | Drug: FGF-2FGF-2 given a minimum of 1 and maximum of 3 times within, approximately, 60 days. |
| Placebo | Placebo comparator | Other: PlaceboEqual concentration of saline is given a minimum of 1 and maximum of 3 times within, approximately, 60 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Dry tympanic membrane perforation of greater than 3 months duration
- If female, post-menopausal or sterile, or if she is of child-bearing potential, must have a negative beta-human chorionic gonadotropin (HCG) test and must be using an adequate form of birth control such as birth control pills, birth control implants, intrauterine devices (IUDs), diaphragms or condoms.
Key exclusion criteria (14 listed)
- Active otitis media or chronic otorrhea from the middle ear
- Subjects receiving radiation therapy, corticosteroids, immunosuppressive agents or chemotherapy
- Subjects who, at study entry, are taking systemic antibiotics
- Subjects who are immunosuppressed
- Subjects experiencing bacterial or viral infection or who may otherwise be febrile
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 |
|---|---|---|
| FGF-2Also: FGF2, Human Fibroblast Growth Factor 2The FGF-2 method of use comprises a pledget of gelatin foam with human fibroblast growth factor-2 (FGF-2) added to the pledget just before topical application to the tympanic membrane, and the use of Tisseel, a fibrin glue used for applications in ear surgery. | Drug | FGF-2 |
| PlaceboAlso: Placebo comparator; sterile salinePlacebo comparator using a sterile saline solution. | Other | Placebo |
Primary outcome
Number of Patients With Tympanic Membrane Closure Following Treatment
Time frame: ~60 days
The efficacy of the treatment is determined by the number of patients whose tympanic membrane perforations closed after study treatments. Subjects from both treatment arms received up to three treatments before determining non-closure of the tympanic membrane.
4 secondary outcomes
Measurement of Changes in Pure-tone Averages
Time frame: Baseline, 60 days
Measurement of Changes in Speech Discrimination Scores
Time frame: Baseline, 60 days
Number of Treatments Required for Closure of the Tympanic Membrane Perforation
Time frame: 60 days
Number of Patients With Normal Mobility of the Eardrum as Assessed by Tympanometry
Time frame: 60 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
D. B. Welling, M.D., Ph.D principal investigator
Massachusetts Eye and Ear
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing FGF-2 in people with Tympanic Membrane Perforation, run by D. Bradley Welling, MD, PhD at 2 sites 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 2 inclusion and 14 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 8 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Patients With Tympanic Membrane Closure Following Treatment (time frame: ~60 days). 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 8 Dec 2025.