Fibroblast Growth Factor Regeneration of Tympanic Membrane Perforations
Primary Purpose
Tympanic Membrane Perforation
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
FGF-2
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Tympanic Membrane Perforation
Eligibility Criteria
Inclusion Criteria:
- Age 18 years and older
- Dry tympanic membrane perforation of at least 6 months duration
- Any person of child-bearing potential, must have a negative beta-HCG test and must agree to use an adequate form of birth control throughout the clinical trial.
Exclusion Criteria:
- 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 or may be with inflammation.
- 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
- Known or suspected allergies to any components used in the study, i.e. porcine collagen
- Subjects who have cholesteatoma mass, or endothelium invasion 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
- Subjects who have undergone prior myringoplasty or tympanoplasty
- Subjects whose TMP is a result of thermal burn, or radiation therapy.
- Subjects who have abnormalities in the auditory ossicles or their linkages
- Subjects having moderate to severe dementia such as Alzheimer's disease or senile dementia
- Subjects whose hearing ability does not improve to bone-conduction hearing on a hearing acuity test using the tentative closure of perforation with a wet cotton ball.
- Subject having residual TM with abnormal form or abnormal shape anatomically
- Subjects having any granulation or soft tissue density due to inflammation, or infection in mastoid antrum determined by CT scanning (Temporal bone CT scanning)
Sites / Locations
- NYU Langone HealthRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Human Fibroblast Growth Factor-2 (FGF-2)
Arm Description
Outcomes
Primary Outcome Measures
TMP Closure Ratio
Determined by otoscopic exam and photographic documentation
Secondary Outcome Measures
Time to Closure of TMP
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Air-Bone Gap (ABG)
Defined as the difference between air-conduction and bone-conduction audiometric thresholds
Mobility of the Tympanic Membrane
As measured by tympanometry
Salvage Rate of FGF-2 in Patients who Fail Placebo
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04960384
Brief Title
Fibroblast Growth Factor Regeneration of Tympanic Membrane Perforations
Official Title
Fibroblast Growth Factor Regeneration of Tympanic Membrane Perforations
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 27, 2022 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is a double blinded, placebo-controlled phase II study evaluating the efficacy of FGF-2 for the treatment of chronic non-healing tympanic membrane perforations (TMP). The documentation of TM closure will be the main efficacy outcome measure. Pretreatment photographs will document the area of the TM perforation and allow measurement of surface areas of the TMP for comparison of pre- and post-treatment. The study will be divided into two phases, the Randomized Treatment phase (part A), and the Unblinded Crossover phase (part B). In part A of the study, subjects will be randomized 1:1 (using simple randomization) to receive FGF-2 or placebo treatment up to 3 treatments. Subjects that fail three study treatments will move on to part B of the study. Subjects who received placebo in part A and failed three placebo treatments will crossover to receive unblinded FGF-2 for up to 3 treatments. Subjects who received FGF-2 in part A and failed three experimental treatments will not have additional FGF-2 treatment, and will move on to study follow up.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tympanic Membrane Perforation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
The investigator and the subject will be blinded to treatment assignment during the Randomized Treatment phase.
Allocation
Randomized
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
Human Fibroblast Growth Factor-2 (FGF-2)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
FGF-2
Intervention Description
The FGF-2 method of use comprises a pledget of gelatin sponge, with human fibroblast growth factor-2 (FGF-2) added to the pledget just before topical application to the tympanic membrane, and the use of fibrin glue used for applications in ear surgery. The concentration of the FGF-2 solution will be 100μg of FGF-2 per 1 mL with an estimated dose of about 20 μg in 0.2ml. Fibrin glue will be applied to secure gelatin sponge after placement according to the size of the membrane perforation. Application of the study treatment will occur at Visit 1 and may be repeated at each follow up visit as needed for a maximum of three treatments in the Randomized Treatment Phase (Visit 1, Visit 2, and Visit 3).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
FGF-2 will be replaced with sterile water to saturate a pledget of gelatin sponge. The method will be otherwise identical to the FGF-2 intervention.
Primary Outcome Measure Information:
Title
TMP Closure Ratio
Description
Determined by otoscopic exam and photographic documentation
Time Frame
up to Day 134
Secondary Outcome Measure Information:
Title
Time to Closure of TMP
Time Frame
up to Day 134
Title
Pure-tone and speech discrimination scores
Description
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time Frame
Pre-treatment (Day 1)
Title
Pure-tone and speech discrimination scores
Description
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time Frame
Post-treatment 1 (Day 22)
Title
Pure-tone and speech discrimination scores
Description
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time Frame
Post-treatment 1 (Day 43)
Title
Pure-tone and speech discrimination scores
Description
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time Frame
Post-treatment 1 (Day 64)
Title
Pure-tone and speech discrimination scores
Description
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time Frame
Post-treatment 1 (Day 85)
Title
Pure-tone and speech discrimination scores
Description
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time Frame
Post-treatment 1 (Day 106)
Title
Pure-tone and speech discrimination scores
Description
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time Frame
Post-treatment 1 (Day 127)
Title
Pure-tone and speech discrimination scores
Description
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time Frame
Post-treatment 1 (Day 134)
Title
Air-Bone Gap (ABG)
Description
Defined as the difference between air-conduction and bone-conduction audiometric thresholds
Time Frame
up to Day 134
Title
Mobility of the Tympanic Membrane
Description
As measured by tympanometry
Time Frame
Day 134
Title
Salvage Rate of FGF-2 in Patients who Fail Placebo
Time Frame
Day 64
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18 years and older
Dry tympanic membrane perforation of at least 6 months duration
Any person of child-bearing potential, must have a negative beta-HCG test and must agree to use an adequate form of birth control throughout the clinical trial.
Exclusion Criteria:
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 or may be with inflammation.
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
Known or suspected allergies to any components used in the study, i.e. porcine collagen
Subjects who have cholesteatoma mass, or endothelium invasion 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
Subjects who have undergone prior myringoplasty or tympanoplasty
Subjects whose TMP is a result of thermal burn, or radiation therapy.
Subjects who have abnormalities in the auditory ossicles or their linkages
Subjects having moderate to severe dementia such as Alzheimer's disease or senile dementia
Subjects whose hearing ability does not improve to bone-conduction hearing on a hearing acuity test using the tentative closure of perforation with a wet cotton ball.
Subject having residual TM with abnormal form or abnormal shape anatomically
Subjects having any granulation or soft tissue density due to inflammation, or infection in mastoid antrum determined by CT scanning (Temporal bone CT scanning)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Elan Dayanov
Phone
212-263-6344
Email
Elan.Dayanov@nyulangone.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Friedmann, MD
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristin Montella
Phone
212-263-8182
Email
Kristin.montella@nyulangone.org
First Name & Middle Initial & Last Name & Degree
David Friedmann, MD
First Name & Middle Initial & Last Name & Degree
J. Thomas Roland, Jr., MD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Only aggregate data will be shared upon reasonable request.
IPD Sharing Time Frame
Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
IPD Sharing Access Criteria
The investigator who proposed to use the data will have access to the data upon reasonable request. Requests should be directed to David.friedmann@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
Learn more about this trial
Fibroblast Growth Factor Regeneration of Tympanic Membrane Perforations
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