Drug-Releasing Cochlear Implant for Hearing Loss

(DEE-REX Trial)

Recruiting at 6 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Cochlear

Must not be taking: Corticosteroids

Disqualifiers: Autoimmune disease, Otitis media, Meniere's, others

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This clinical study will test a new type of cochlear implant known as CI632D. This experimental cochlear implant has been designed to slowly release a drug called dexamethasone. Dexamethasone works to ease inflammation and reduce tissue injury, which is common after any type of surgery. The goal is to learn if the dexamethasone in the CI632D implant lessens these reactions inside the ear following surgery and if this makes the implant work as well, or even better, in improving hearing than what would be expected with a standard cochlear implant. The study will be conducted in adults with sensorineural hearing loss, a type of hearing loss caused by damage to the inner ear or auditory nerve (the nerve that carries sound signals from the ear to the brain). The study participants will receive the CI632D experimental implant and will complete tests to see how well they are hearing and how well the implant is working.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on active immunosuppressive therapy, you may not be eligible to participate.

What data supports the idea that Drug-Releasing Cochlear Implant for Hearing Loss is an effective treatment?

The available research shows that using a drug-releasing cochlear implant, specifically with dexamethasone, can help improve hearing outcomes. In one study, patients who received dexamethasone with their cochlear implants had better hearing preservation compared to those who did not receive the drug. For example, 62% of patients who received steroids had partial or complete hearing preservation, while only 33% of those without steroids achieved similar results. Another study found that dexamethasone released from the implant helped protect the ear from damage during the implant process, which can lead to better long-term hearing results. These findings suggest that the drug-releasing cochlear implant is more effective than implants without the drug. ^{1 2 3 4 5}

What safety data exists for the drug-releasing cochlear implant?

Several studies have evaluated the safety of dexamethasone-eluting cochlear implants. In non-human primates, the dexamethasone-eluting electrode showed a protective anti-inflammatory effect. In guinea pigs, dexamethasone-eluting electrodes were found to be safe, with no bacterial infection or significant tissue growth observed. The drug was released in a controlled manner, maintaining stable concentrations in the perilymph without accumulating in cochlear tissue. These findings suggest that the dexamethasone-eluting cochlear implant is safe and effective in reducing inflammation and preserving hearing. ^{5 6 7 8 9}

Is the drug Dexamethasone a promising treatment for hearing loss with cochlear implants?

Yes, Dexamethasone is promising because it can be released in a controlled way from cochlear implants to protect the ear from damage during surgery, reduce inflammation, and improve the performance of the implants. ^{1 2 3 9 10}

Research Team

Aaron Parkinson, PhD

Principal Investigator

Cochlear

Eligibility Criteria

Adults with sensorineural hearing loss, which is caused by damage to the inner ear or auditory nerve, are eligible for this trial. Participants must be suitable candidates for cochlear implant surgery.

Inclusion Criteria

Willing and able to provide written informed consent.

I have received the pneumococcal vaccine as recommended.

Pure-tone average unaided threshold (500 through 4000 Hz) ≥ 30 dB HL, in the contralateral ear

Exclusion Criteria

I have had bacterial meningitis before.

I have brain lesions or deafness in the ear I plan to have an implant in.

I am allergic to dexamethasone or corticosteroids.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation

Participants receive the CI632D experimental implant

1 day

1 visit (in-person)

Postactivation Monitoring

Participants are monitored for changes in hearing and implant performance at 3-, 6-, and 12-months postactivation

12 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dexamethasone (Corticosteroid)

Trial Overview The study tests a new cochlear implant (CI632D) that releases dexamethasone to reduce inflammation and tissue injury post-surgery. The aim is to see if it improves hearing more effectively than standard implants.

Participant Groups

Group I: Drug-eluting electrode array (CI632D) Experimental Treatment 2 Interventions

Participants will be implanted with the slim modiolar dexamethasone-eluting electrode array.

Dexamethasone is already approved in Canada, Japan for the following indications:

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

Cochlear

Lead Sponsor

Trials

96

Recruited

6,300+

Headquarters

Sydney, Australia

Dig Howitt

Cochlear

Chief Executive Officer since 2018

BE (Hons), MBA

Michael del Prado

Cochlear

Chief Medical Officer since 2022

MD, MSc, FRACP, FAAHMS, FAICD

University of Iowa

Collaborator

Trials

486

Recruited

934,000+

LWB Consulting

Collaborator

Trials

2

Recruited

110+

Althea Anagnostopoulos Harrington

Collaborator

Trials

2

Recruited

110+

MV Clinical Research, LLC

Collaborator

Trials

2

Recruited

110+

Findings from Research

Local drug application to the inner ear, such as through intracochlear delivery, offers significant advantages over systemic delivery, particularly in enhancing cochlear implant (CI) rehabilitation by delivering therapeutic agents directly to the site of action.

In two case reports, patients with cochlear implants benefited from the intracochlear placement of a biocompatible, resorbable drug delivery system that released dexamethasone, leading to improved speech discrimination and reduced impedance, demonstrating the potential for targeted therapy in managing CI-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intracochlear drug delivery in combination with cochlear implants : Current aspects]. Plontke, SK., Götze, G., Rahne, T., et al.[2018]

Dexamethasone can be effectively released in a controlled manner from silicone used in cochlear implant electrode carriers, which may help protect residual low-frequency hearing after implantation.

In both in vitro and in vivo studies, the sustained release of dexamethasone was observed, lasting up to 20 weeks in vitro and 1 week in vivo, indicating potential for improved safety and performance of cochlear implants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo pharmacokinetic study of a dexamethasone-releasing silicone for cochlear implants. Liu, Y., Jolly, C., Braun, S., et al.[2018]

Local drug application to the inner ear, such as through cochlear implants, offers advantages over systemic delivery by improving drug targeting and reducing side effects, particularly for therapies like glucocorticosteroids and neurotrophins.

Two case reports demonstrated successful use of a biocompatible, resorbable drug-delivery system for controlled release of dexamethasone in cochlear implant patients, which helped address issues like reduced speech discrimination and increased impedance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracochlear drug delivery in combination with cochlear implants : Current aspects. Plontke, SK., Götze, G., Rahne, T., et al.[2019]

In a study of 147 adult patients undergoing cochlear implantation, those who received steroids (either dexamethasone or a combination with prednisone) showed significantly better hearing preservation, with 62% achieving partial or complete hearing preservation compared to only 33% in the control group without steroids.

The effectiveness of hearing preservation varied by cochlear implant brand, with Med-El and Advanced Bionics patients showing better outcomes (45% and 43% respectively) compared to those with Oticon implants (20%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Effect of Steroids for Hearing Preservation in Cochlear Implantation: Conclusions Based on Three Cochlear Implant Systems and Two Administration Regimes. Skarżyńska, MB., Kołodziejak, A., Gos, E., et al.[2022]

In a study of 35 adult patients undergoing cochlear implantation, those receiving intravenous dexamethasone showed a high rate of partial hearing preservation (77.8%), indicating its effectiveness in maintaining residual hearing post-surgery.

The combination of intravenous dexamethasone and oral prednisone also resulted in significant hearing preservation (61.5%), while the control group without steroid treatment had a higher incidence of no measurable hearing (38.5%) after 12 months, highlighting the potential benefits of steroid therapy in cochlear implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Effect of Steroid Therapy on Preserving Residual Hearing after Cochlear Implantation with the Advanced Bionics HiRes Ultra 3D Cochlear Implant System. Skarzynska, MB., Kolodziejak, A., Gos, E., et al.[2022]

The dexamethasone-eluting electrode (DEXEL) demonstrated a protective anti-inflammatory effect in normal hearing macaques, resulting in lower threshold shifts and impedance values compared to conventional cochlear implants after 6 months.

The DEXEL group showed significantly higher electrically evoked compound action potential (eCAP) amplitudes and reduced tissue reactions like fibrosis and ossification, indicating improved safety and efficacy in preserving hearing function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cochlear Implantation With a Dexamethasone Eluting Electrode Array: Functional and Anatomical Changes in Non-Human Primates. Manrique-Huarte, R., Zulueta-Santos, C., Calavia, D., et al.[2021]

Incorporating dexamethasone (DXM) into cochlear implant arrays does not affect the insertion forces, indicating that it can be safely used without increasing the risk of trauma during the implantation process.

The study tested four different cochlear implant models with a total of 140 insertions, and found that the DXM-loaded arrays maintained similar friction forces compared to drug-free models, suggesting potential benefits for reducing inflammation and fibrosis post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of embedded dexamethasone in cochlear implant array on insertion forces in an artificial model of scala tympani. Nguyen, Y., Bernardeschi, D., Kazmitcheff, G., et al.[2018]

In a study using guinea pigs, dexamethasone-eluting silicone rods were found to be safe for use in cochlear implants, showing no signs of bacterial infection or increased macrophage presence, which indicates a low risk of inflammation.

The study demonstrated that the dexamethasone-eluting electrodes resulted in less hearing threshold shift (1 dB) compared to non-eluting electrodes (10 dB), suggesting that the dexamethasone may help mitigate hearing loss associated with electrode insertion trauma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cochlear implant and inflammation reaction: Safety study of a new steroid-eluting electrode. Astolfi, L., Simoni, E., Giarbini, N., et al.[2018]

Dexamethasone can be effectively embedded in cochlear implant electrode carriers, allowing for controlled and sustained release of the drug over several weeks, which helps reduce inflammation after surgery.

Higher concentrations of dexamethasone (1% and 10%) resulted in significantly greater and longer-lasting drug levels in the perilymph compared to lower concentrations, suggesting that a dose range of 50 to 100 ng/ml is effective for managing inflammation during cochlear implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term in vivo Release Profile of Dexamethasone-Loaded Silicone Rods Implanted Into the Cochlea of Guinea Pigs. Liebau, A., Schilp, S., Mugridge, K., et al.[2020]

A single dose of a sustained release dexamethasone hydrogel administered one day before cochlear implantation significantly reduced hearing threshold shifts at various frequencies, indicating improved hearing preservation post-surgery.

Increased outer hair cell counts were observed in the cochlear apex of guinea pigs treated with dexamethasone, suggesting that timely glucocorticoid application can enhance cochlear health, although it was also associated with a higher rate of electrode translocation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of sustained release dexamethasone hydrogels in hearing preservation cochlear implantation. Honeder, C., Zhu, C., Schöpper, H., et al.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Intracochlear drug delivery in combination with cochlear implants : Current aspects]. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

In vitro and in vivo pharmacokinetic study of a dexamethasone-releasing silicone for cochlear implants. [2018]

3. Germany pubmed.ncbi.nlm.nih.gov

Intracochlear drug delivery in combination with cochlear implants : Current aspects. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The Clinical Effect of Steroids for Hearing Preservation in Cochlear Implantation: Conclusions Based on Three Cochlear Implant Systems and Two Administration Regimes. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The Clinical Effect of Steroid Therapy on Preserving Residual Hearing after Cochlear Implantation with the Advanced Bionics HiRes Ultra 3D Cochlear Implant System. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Cochlear Implantation With a Dexamethasone Eluting Electrode Array: Functional and Anatomical Changes in Non-Human Primates. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Effect of embedded dexamethasone in cochlear implant array on insertion forces in an artificial model of scala tympani. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Cochlear implant and inflammation reaction: Safety study of a new steroid-eluting electrode. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Long-Term in vivo Release Profile of Dexamethasone-Loaded Silicone Rods Implanted Into the Cochlea of Guinea Pigs. [2020]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of sustained release dexamethasone hydrogels in hearing preservation cochlear implantation. [2018]