Clinical trial NCT06698419: RADA16 on Mastoid Cavity Epithelialization
Official title: A Prospective Study: The Effect of RADA16 on Mastoid Cavity Epithelialization After Canal Wall Down Mastoidectomy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Delayed Wound Healing
Keywords: Mastoidectomy
Healing
Biologic
Mastoid cavity
Mastoid cavity disease
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: 3-D Matrix UK Ltd.
First posted: 2024-11-21
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly allocated to the experimental group or the control group. All participants will undergo a canal wall down mastoidectomy in standard fashion. Participants in the experimental group will receive RADA16 gel in the mastoid cavity at the conclusion of the surgery whereas participants in the control group will not.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to see if the application of RADA16 gel can expedite and improve the healing process in participants after canal wall down mastoidectomy. The main questions are:

* Does application of RADA16 in the mastoid cavity after canal wall down mastoidectomy lead to faster healing (i.e. epithelialization)?
* Is application of RADA16 in the mastoid cavity after canal wall down mastoidectomy associated with a decreased need for medications after surgery (i.e. antibiotics, steroids), less frequent in-office debridements, and less postoperative appointments?

Researchers will compare the healing outcomes in participants treated with RADA16 gel to those in a control group who do not receive the treatment.

Participants will:

* Undergo canal wall down mastoidectomy as recommended regardless of participation in the clinical trial
* Follow-up postoperatively for clinical assessment at 1 month, 2 months, 3 months, 6 months, 1 year, 18 months, and 2 years. Participants may follow-up more frequently as needed.

Detailed description: Canal wall-down mastoidectomy is a commonly performed procedure for the treatment of cholesteatoma and chronic otitis media which involves elimination of the posterior wall of the external auditory canal and creation of a mastoid cavity. Unlike its canal wall-up counterpart, canal wall-down mastoidectomy allows for exteriorization and removal of cholesteatoma and middle ear disease in otherwise difficult-to-access middle ear subsites (e.g., sinus tympani and lateral epitympanum), and improved surveillance of these spaces post-operatively.

While there are many benefits to canal wall-down mastoidectomy in the right patient, the creation of a mastoid cavity is not without pitfalls. Normally, the tympanic cavity and mastoid air cells are covered in mucosal epithelium which is important in middle ear ventilation, protection from infection, and sound transmission to the inner ear. A mastoid cavity requires life-long maintenance and care and periodic visits to an otolaryngologist for debridement and surveillance. In creation of the mastoid cavity, the mucosa lining tympanic cavity and mastoid air cells is often removed along with cholesteatoma or other middle ear disease leaving exposed bone. Maturation of the mastoid cavity requires re-epithelization of the cavity which can take months to years to occur \[2\]. Inadequate or delayed epithelialization results in an "unstable" mastoid cavity which occurs in 20 to 60% of patients depending on the study \[2-4\]. Formation of granulation tissue and adhesions trap debris and lead to excessive crusting, chronic otorrhea, and intolerance to water exposure which further hinders mastoid cavity healing. In the researchers' experience, these patients often require more frequent office visits for debridement, application of ototopical agents, in-office cauterization, and revision mastoidectomy under general anesthesia in some cases.

Creation of a mastoid cavity requires making a wide enough cavity to allow for adequate ventilation, facilitate cavity inspection, and promote a self-cleaning environment. Other anatomic factors important for the surgeon include creating a mastoid cavity that is oval-shaped with a low facial ridge \[5\]. Because maturation of the mastoid cavity requires complete epithelization, a variety of methods have been explored to facilitate this process including application of a gelatin film \[6\], silastic sheeting \[7\], pedicled postauricular periosteal flap \[8\], and poly-N-acetyl-glucosamine sheet with fibrin glue \[9\]. At our institution and many others, mastoid cavities are packed with absorbable gelatin sponge (Gelfoam) which provides structural support for the newly formed mastoid cavity by securing soft tissue and grafts in place.

To date, there are no studies evaluating the use of RADA16 gel in human otologic surgery. RADA16 is a viscous solution of synthetic peptides that self-assemble into a transparent hydrogel matrix at physiological pH, mimicking the native extracellular matrix \[10\]. This unique property has enabled RADA16 to be adapted for various clinical applications. The biologic scaffold created by RADA16 acts as a physical barrier over wounds, inhibiting blood flow and promoting hemostasis. Its effectiveness has been demonstrated in various cardiovascular, gastrointestinal, and otolaryngologic procedures specifically endonasal \[11-17\].

The hydrogel matrix of RADA16 not only serves as a barrier but also acts as a biologic scaffold that supports wound healing, cell proliferation, and tissue regeneration \[18\]. Numerous in vivo studies have highlighted RADA16's potential as a wound healing agent. For example, it has shown promise in promoting mucosal regeneration after gastric ulcer formation \[19\], colon injury in a rat model \[20\], periodontal disease \[21\], and following endoscopic excision of gastrointestinal lesions \[17\]. Animal models have also demonstrated RADA16's ability to prevent scarring and adhesion formation, specifically in preventing esophageal stricture after submucosal resection \[22\]. In sinonasal surgery, RADA16 has proven beneficial in enhancing wound healing, preventing adhesion formation, and minimizing crusting \[13, 23\]. In a sheep model, RADA16 application to nasal mucosal defects led to reduced adhesion formation and accelerated healing \[24\]. More pertinent to this investigation, a study using a middle ear rodent model revealed that cultured middle ear epithelial cells treated with RADA16 were able to survive and repair mucosal defects, unlike those not treated with RADA16 \[25\].

Given the previous studies which include improved mucosal wound healing in the sinonasal cavity and a promising middle ear rodent study, researchers' aim to investigate and compare mastoid cavity epithelization rates after canal wall down mastoidectomy with and without the intraoperative application of RADA16 gel.

Eligibility criteria: Inclusion Criteria:

* English-speaking adults over the age of 18 years who require a canal wall down mastoidectomy for any reason including cholesteatoma, chronic suppurative middle ear disease, and neoplasm.
* Participants with history of canal wall up mastoidectomy who now require canal wall down mastoidectomy for any reason.

Exclusion Criteria:

* History of chronic immunodeficiency and autoimmune disease
* History of head and neck radiation
* Active tobacco use
* History of coronary artery disease
* History of peripheral vascular disease
* History of diabetes mellitus
* Known allergy to RADA16 gel or its components
* Vulnerable populations including children, neonates, pregnant women, prisoners, institutionalized individuals, and other individuals who are unable to provide informed consent

Primary outcomes:
measure: Time to Complete Mastoid Cavity Epithelialization at 1 Month
timeFrame: Baseline and Postoperative Month 1
measure: Time to Complete Mastoid Cavity Epithelialization at 2 Months
timeFrame: Baseline and Postoperative Month 2
measure: Time to Complete Mastoid Cavity Epithelialization at 3 Months
timeFrame: Baseline and Postoperative Month 3
measure: Time to Complete Mastoid Cavity Epithelialization at 6 Months
timeFrame: Baseline and Postoperative Month 6
measure: Time to Complete Mastoid Cavity Epithelialization at 1 Year
timeFrame: Baseline and Postoperative Year 1
measure: Time to Complete Mastoid Cavity Epithelialization at 18 Months
timeFrame: Baseline and Postoperative Month 18
measure: Time to Complete Mastoid Cavity Epithelialization at 2 Years
timeFrame: Baseline and Postoperative Year 2
Secondary outcomes:
measure: Total Number of Medications Prescribed Up To Complete Epithelialization
timeFrame: Baseline to complete epithelialization, up to 2 years
measure: Total Number of Mastoid Cavity Debridements Up to Complete Epithelialization
timeFrame: Baseline to complete epithelialization, up to 2 years
measure: Total Number of Postoperative Visits Up to Complete Epithelialization
timeFrame: Baseline to complete epithelialization, up to 2 years
Other outcomes:
Locations:
Study officials:
affiliation: University of Florida
name: Rex Haberman, MD
role: PRINCIPAL_INVESTIGATOR
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