Clinical trial NCT02307916: Fibroblast Growth Factor Regeneration of Tympanic Membrane Perforations
Official title: Fibroblast Growth Factor Regeneration of Tympanic Membrane Perforations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tympanic Membrane Perforation
Keywords: tympanic membrane perforation
ear drum
hole
Lead sponsor: Massachusetts Eye and Ear Infirmary
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2014-12-04
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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). 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.

Eligibility criteria: Inclusion Criteria:

1. Dry tympanic membrane perforation of greater than 3 months duration
2. 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.

Exclusion Criteria:

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
* 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

Primary outcomes:
measure: Number of Patients With Tympanic Membrane Closure Following Treatment
timeFrame: ~60 days
Secondary outcomes:
measure: Measurement of Changes in Pure-tone Averages
timeFrame: Baseline, 60 days
measure: Measurement of Changes in Speech Discrimination Scores
timeFrame: Baseline, 60 days
measure: Number of Treatments Required for Closure of the Tympanic Membrane Perforation
timeFrame: 60 days
measure: Number of Patients With Normal Mobility of the Eardrum as Assessed by Tympanometry
timeFrame: 60 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts Eye and Ear
state: Massachusetts
city: Lackland Air Force Base
country: United States
facility: Wilford Hall, Lackland Airforce Base
state: Texas
Study officials:
affiliation: Massachusetts Eye and Ear
name: D. B. Welling, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References: