RADA16 on Mastoid Cavity Epithelialization

November 18, 2024 updated by: University of Florida

A Prospective Study: The Effect of RADA16 on Mastoid Cavity Epithelialization After Canal Wall Down Mastoidectomy

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

14

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: RADA16 Group
Participants will undergo canal wall down mastoidectomy in standard fashion. All participants will have absorbable gelatin sponge placed into the mastoid cavity which is standard care. Only participants in this arm will receive RADA16 gel into the mastoid cavity before placement of the gelatin sponge.
Device: RADA16 gel application into mastoid cavity
A single application of RADA16 gel will be applied along the surface of the mastoid cavity intraoperatively prior to insertion of gelatin sponge packing. Application will involve a thin layer of gel just enough to cover the entire surface of the cavity.
Other Names:
  • PuraGel
No Intervention: Control Group
Participants will undergo canal wall down mastoidectomy in standard fashion. All participants will have absorbable gelatin sponge placed into the mastoid cavity which is standard care. Participants in this arm will not receive RADA16 gel.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Complete Mastoid Cavity Epithelialization at 1 Month
Time Frame: Baseline and Postoperative Month 1
The mastoid cavity will be evaluated postoperatively using an operative microscope. The principal investigator will record the otoscopic exam which will be saved as a digital file on a password-secured server. Two separate investigators who are masked to participant arm allocation will view the recorded exam and evaluate the mastoid cavity for complete epithelialization.
Baseline and Postoperative Month 1
Time to Complete Mastoid Cavity Epithelialization at 2 Months
Time Frame: Baseline and Postoperative Month 2
The mastoid cavity will be evaluated postoperatively using an operative microscope. The principal investigator will record the otoscopic exam which will be saved as a digital file on a password-secured server. Two separate investigators who are masked to participant arm allocation will view the recorded exam and evaluate the mastoid cavity for complete epithelialization.
Baseline and Postoperative Month 2
Time to Complete Mastoid Cavity Epithelialization at 3 Months
Time Frame: Baseline and Postoperative Month 3
The mastoid cavity will be evaluated postoperatively using an operative microscope. The principal investigator will record the otoscopic exam which will be saved as a digital file on a password-secured server. Two separate investigators who are masked to participant arm allocation will view the recorded exam and evaluate the mastoid cavity for complete epithelialization.
Baseline and Postoperative Month 3
Time to Complete Mastoid Cavity Epithelialization at 6 Months
Time Frame: Baseline and Postoperative Month 6
The mastoid cavity will be evaluated postoperatively using an operative microscope. The principal investigator will record the otoscopic exam which will be saved as a digital file on a password-secured server. Two separate investigators who are masked to participant arm allocation will view the recorded exam and evaluate the mastoid cavity for complete epithelialization.
Baseline and Postoperative Month 6
Time to Complete Mastoid Cavity Epithelialization at 1 Year
Time Frame: Baseline and Postoperative Year 1
The mastoid cavity will be evaluated postoperatively using an operative microscope. The principal investigator will record the otoscopic exam which will be saved as a digital file on a password-secured server. Two separate investigators who are masked to participant arm allocation will view the recorded exam and evaluate the mastoid cavity for complete epithelialization.
Baseline and Postoperative Year 1
Time to Complete Mastoid Cavity Epithelialization at 18 Months
Time Frame: Baseline and Postoperative Month 18
The mastoid cavity will be evaluated postoperatively using an operative microscope. The principal investigator will record the otoscopic exam which will be saved as a digital file on a password-secured server. Two separate investigators who are masked to participant arm allocation will view the recorded exam and evaluate the mastoid cavity for complete epithelialization.
Baseline and Postoperative Month 18
Time to Complete Mastoid Cavity Epithelialization at 2 Years
Time Frame: Baseline and Postoperative Year 2
The mastoid cavity will be evaluated postoperatively using an operative microscope. The principal investigator will record the otoscopic exam which will be saved as a digital file on a password-secured server. Two separate investigators who are masked to participant arm allocation will view the recorded exam and evaluate the mastoid cavity for complete epithelialization.
Baseline and Postoperative Year 2

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Number of Medications Prescribed Up To Complete Epithelialization
Time Frame: Baseline to complete epithelialization, up to 2 years
The total number of medications prescribed postoperatively to promote mastoid cavity healing will be assessed with focus on antibiotics and steroids.
Baseline to complete epithelialization, up to 2 years
Total Number of Mastoid Cavity Debridements Up to Complete Epithelialization
Time Frame: Baseline to complete epithelialization, up to 2 years
The total number of in-office mastoid cavity debridements will be recorded and assessed. Participants with faster and more robust healing are expected to require less in-office debridements.
Baseline to complete epithelialization, up to 2 years
Total Number of Postoperative Visits Up to Complete Epithelialization
Time Frame: Baseline to complete epithelialization, up to 2 years
The total number of postoperative visits (including set time points at 1 month, 2 months, 3 months, 9 months, 1 year, 18 months, and 2 years) will be recorded and assessed. Participants with faster and more robust healing are expected to not need additional visits, specifically for mastoid cavity healing related problems.
Baseline to complete epithelialization, up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Florida

Collaborators

3-D Matrix Medical Technology

Investigators

  • Principal Investigator: Rex Haberman, MD, University of Florida

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2025

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

November 18, 2024

First Submitted That Met QC Criteria

November 18, 2024

First Posted (Estimated)

November 21, 2024

Study Record Updates

Last Update Posted (Estimated)

November 21, 2024

Last Update Submitted That Met QC Criteria

November 18, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • IRB202401064

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is no current plan to share IPD with other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Delayed Wound Healing

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Chile

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe