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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
52
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).
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.
NYU Langone Health
New York, New York, United States
TMP Closure Ratio
Determined by otoscopic exam and photographic documentation
Time frame: up to Day 134
Time to Closure of TMP
Time frame: up to Day 134
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time frame: Pre-treatment (Day 1)
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time frame: Post-treatment 1 (Day 22)
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time frame: Post-treatment 1 (Day 43)
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time frame: Post-treatment 1 (Day 64)
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time frame: Post-treatment 1 (Day 85)
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time frame: Post-treatment 1 (Day 106)
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time frame: Post-treatment 1 (Day 127)
Pure-tone and speech discrimination scores
Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz). S
Time frame: Post-treatment 1 (Day 134)
Air-Bone Gap (ABG)
Defined as the difference between air-conduction and bone-conduction audiometric thresholds
Time frame: up to Day 134
Mobility of the Tympanic Membrane
As measured by tympanometry
Time frame: Day 134
Salvage Rate of FGF-2 in Patients who Fail Placebo
Time frame: Day 64
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