Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06448039 |
| Other study ID # |
2024P001401 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
June 15, 2024 |
| Est. completion date |
December 30, 2025 |
Study information
| Verified date |
June 2024 |
| Source |
Massachusetts Eye and Ear Infirmary |
| Contact |
Christopher G. Wood |
| Phone |
857-991-8680 |
| Email |
cgwood[@]meei.harvard.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The goal of this clinical trial is to compare the application of fibroblast growth factor 2
(FGF2) with normal saline for the healing of chronic tympanic membrane (TM) perforations.
This is an extension of a prior study.
The main question it aims to answer is: Will modifications to our prior surgical trial
provide higher success rates in obtaining complete closure of chronic tympanic membrane
perforations? Twenty participants will be randomized in a controlled study to FGF2 or saline
in a 3:1 ratio and the total tympanic membrane closure compared.
Description:
Background
The use of topically applied growth factors to promote TM closure has been suggested as an
attractive alternative to conventional tympanoplasty. Previous clinical studies have reported
a 92% and 98% complete closure rate of chronic tympanic membrane perforations with
application of topical FGF-22 (Hakuba et al., Kanemaru et al). The investigators recently
published a study a double-blinded, randomized placebo-controlled phase 2 clinical trial of
54 patients with chronic TM perforations also applying topical FGF-2 with saline as the
control. Unlike prior studies the investigators found no statistically significant difference
between FGF-2 (57.5%) and saline control TM (71.4%) closure rates (P value = 0.36).
The current study is proposed to examine healing rates with topical application of FGF-2 with
surgical modifications to our prior study in the attempt to mirror the Japanese studies
excellent results. The long-term goal is to repair TM perforations with nonsurgical topical
application of the appropriate factors to avoid surgery, general anesthesia, and
hospitalization. A secondary aim is to maintain hearing and to prevent complications of TMP.
Surgical modifications in this limited study of 20 patients randomized to active (FGF-2) or
placebo (saline) treatment include 1) ensuring that no middle ear discharge is present at the
time of the procedure, 2) placing a cotton pledget in the middle ear prior to rimming the
perforation, 3) removing any tympanosclerotic tympanic membrane that abuts the perforation,
4) placing a layer of test article in the middle ear medial to the perforation and lateral to
the perforation prior to adding a fibrin glue, 5) using up to 4 applications of the test
article, and 6) the procedure will be performed by one surgeon only to ensure complete
adherence to prescribed techniques and reduce surgeon variability.
Specific Aims and Objectives
The primary outcome is complete the closure of chronic tympanic membrane perforations
evaluated at six months post treatment by photo-documentation and tympanometry. Secondary
measures will include a) changes in pure tone and speech audiometry and b) wideband TM
acoustic absorption.
General Description of Study Design
Randomized double-blinded placebo-controlled treatment of 20 patients with chronic (>6
month), dry tympanic membrane perforations will be repaired with a gelatin sponge soaked with
FGF2 or saline in a 3:1 ratio, then covered with a fibrin glue. Up to four applications will
be administered at 3 week intervals or until complete healing is observed.
Subject Enrollment Patients who present to participating otologist's MEE clinics with a
chronic (6 months or longer), dry tympanic membrane perforation will be invited to
participate by the investigators.
Study Procedure
Consenting subjects will be placed in the supine position in the minor operating suite of the
Otology Clinic at MEE. The ear with the chronic perforation will be visualized with binocular
microscopy and image will be taken for measurement of the TM perforation (time point 0). Any
cerumen or debris occluding vision of the complete circumference of the central perforation
will be removed. If the complete circumference of the central perforation cannot be
visualized, an endoscope may be used. Complete view around the circumference of the
perforation is required to proceed. If the perforation is a marginal perforation, the
procedure will not proceed. Likewise, if there is discharge from the perforation or
excessively thickened diseased mucosa, the procedure will be terminated.
Anesthesia of the clean, dry, chronic TM perforation will be accomplished by placing 4%
lidocaine gel impregnated cotton against the TM with care to cover the edges of the
perforation completely. The gel is left in place for a minimum of 15 minutes measured with a
room timer. Following removal of the lidocaine gel cotton pledget, the anesthesia is tested
with a sharp fine straight pick by creating postage stamp perforations around the
circumference of the perforation. To ensure sufficient anesthesia, an injection of 1%
lidocaine directly into the external auditory canal may be given if necessary to reduce pain.
The rim of the perforation is then completely removed with small cup forceps. If an area of
hyalinized TM or tympanosclerosis is abutting the perforation, the tympanosclerosis will be
removed also.
After rimming the perforation is complete, saline or FGF2 soaked gelatin foam is placed
through the perforation into the middle ear to fill the space medial to the perforation and
surrounding it. A second layer of test article soaked gelatin is placed lateral to the
perforation
Next a thin layer of fibrin glue is sprayed over the perforation and gelatin foam and allowed
to congeal. A cotton ball is placed in the external meatus and the procedure terminated.
The patient returns for follow up in 3 weeks (+/- 1 week) for re-inspection of the
perforation. The procedure may be repeated up to 3 more times if the perforation has not
completely healed at follow up out to 9 weeks. If the perforation is completely healed and
confirmed by pneumatic otoscopy, the patient will return 6 months from the procedure for
follow up audiogram and tympanometry.
Any risks of the medical procedure to be performed will be explained thoroughly to patients.
Statistical Analysis
The null hypothesis is that there is no difference between 40 previously treated FGF-2
subjects (original surgical group 1) and this study (adjusted surgical group 2). From our
prior study, FGF-2 treated group 1 had an effective closure rate of 40% in 40 patients. To
show a difference with 80% closure rate in group 2, the investigators need 14 subjects at
alpha 0.05, beta at 0.2 and power of .80. If 20 subjects are enrolled, 5 will receive placebo
and 15 FGF-2. Of the 15 subjects receiving FGF-2, if one withdraws (similar to our prior
study), 14 FGF-2 treated subjects suffice for the analysis. If 80% or more FGF2 show TMP
complete closure with durability to six months, the investigators will propose further phase
II clinical trials.
Secondary outcomes of hearing and tympanic membrane mobility will be measured with audiometry
and tympanometry. Pure tone averages will be analyzed using ordinary linear regression and
speech discrimination will be analyzed using quantile regression. Tympanometry and wide band
immittance will be descriptive only in this small cohort.
Monitoring and Quality Assurance
The quality, data, and safety will be monitored regularly by an independent medical monitor.
Monitoring and oversight will be maintained and documented through monthly meetings that will
include the PI and study staff. Adverse events if any will be reported according to MGB
guidelines.
