Cochlear Implant Stimulation for Usher Syndrome

Recruiting in Palo Alto (17 mi)

+3 other locations

Overseen by Shuman He, MD, PhD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Waitlist Available

Sponsor: Ohio State University

Disqualifiers: Severe medical comorbidities, electrode malposition, others

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

Usher syndrome (USH) causes extensive degeneration in the cochlear nerve (CN), especially in CN fibers innervating the base of the cochlea. As the first step toward developing evidence-based practice for managing implant patients with USH, this study evaluates local neural health, as well as the neural encoding of temporal and spectral cues at the CN in implanted patients with USH. Aim 1 will determine local CN health in patients with USH by assessing the sensitivity of the electrically evoked compound action potential to changes in interphase gap and pulse polarity. Aim 2 will determine group differences in neural encoding of temporal and spectral cues at the CN between patients with USH and patients with idiopathic hearing loss. Aim 3 will use supervised machine learning techniques to develop an objective tool for assessing the electrode-neuron interface at individual electrode locations.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment for Usher Syndrome using cochlear implants and experimental stimulation parameters?

Cochlear implants have been successful in providing partial hearing to over 120,000 people worldwide, including children who develop nearly normal language skills. Additionally, electroacoustic stimulation (EAS) has shown auditory benefits in children with limited low-frequency hearing, suggesting potential effectiveness for similar conditions. ^{1 2 3 4 5}

Is cochlear implant stimulation safe for humans?

Research on cochlear implants, including studies on animals, shows that there can be risks such as surgical trauma and damage to the inner ear structures. However, these findings help improve the design and safety of cochlear implants for human use. ^{4 6 7 8 9}

How does the cochlear implant stimulation treatment for Usher Syndrome differ from other treatments?

This treatment is unique because it involves experimental manipulation of cochlear implant stimulation parameters to improve hearing by focusing electrical signals more precisely on the auditory nerve, potentially reducing signal 'blurring' and enhancing speech recognition, especially in noisy environments. ^{10 11 12 13 14}

Research Team

Shuman He, MD, PhD

Principal Investigator

Ohio State University

Eligibility Criteria

This trial is for individuals with Usher Syndrome or idiopathic hearing loss who have used a cochlear implant for at least 6 months. It's not suitable for those with severe medical conditions or issues with the position of their cochlear implant electrodes.

Inclusion Criteria

You have had a cochlear implant for at least 6 months.

I have been diagnosed with Usher syndrome or have hearing loss without a known cause.

Exclusion Criteria

The electrodes are not placed correctly or have moved, as shown in the imaging tests.

I have severe health conditions besides my cancer.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Evaluation of local neural health and neural encoding of temporal and spectral cues at the cochlear nerve in implanted patients with Usher syndrome

2 years

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Experimental manipulation of stimulation parameters (Other)

Trial Overview The study aims to understand how well the auditory nerve functions in patients with Usher Syndrome using cochlear implants by manipulating stimulation settings and measuring responses. It also seeks to develop a tool to assess the connection between electrodes and nerves.

Participant Groups

Group I: Usher Syndrome Experimental Treatment 1 Intervention

Adult and pediatric cochlear implant users with Usher syndrome

Group II: Idiopathic Hearing Loss Active Control 1 Intervention

Adult and pediatric cochlear implant users with idiopathic hearing loss

Experimental manipulation of stimulation parameters is already approved in Canada for the following indications:

Approved in Canada as Cochlear implant for:

• Severe to profound sensorineural hearing loss
• Single-sided deafness
• Bilateral profound sensorineural hearing loss in children

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

Dr. John J. Warner

Ohio State University

Chief Executive Officer since 2023

MD, MBA

Dr. Peter Mohler

Ohio State University

Chief Medical Officer since 2023

PhD in Molecular Biology

National Institute on Deafness and Other Communication Disorders (NIDCD)

Collaborator

Trials

377

Recruited

190,000+

Joshua M. Levy

National Institute on Deafness and Other Communication Disorders (NIDCD)

Chief Medical Officer

MD, MPH, MS

Debara L. Tucci

National Institute on Deafness and Other Communication Disorders (NIDCD)

Chief Executive Officer since 2019

MD, MS, MBA

Findings from Research

Cochlear implants have successfully provided partial hearing to over 120,000 people worldwide, including many children who can develop nearly normal language skills, highlighting their efficacy in treating hearing loss.

The success of cochlear implants is attributed to a collaborative effort among engineers, scientists, and healthcare professionals, focusing on system design, safety, and integration, which sets a model for developing other neural prostheses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cochlear implants: system design, integration, and evaluation. Zeng, FG., Rebscher, S., Harrison, W., et al.[2022]

In a study of 17 children with limited low-frequency hearing who underwent cochlear implantation (CI), electroacoustic stimulation (EAS) rehabilitation showed potential benefits, particularly in noisy environments, enhancing speech perception compared to CI-only mode.

Successful EAS rehabilitation was achieved in 9 out of 21 ears, with the postoperative low-frequency pure-tone average identified as a key predictive factor for better outcomes, suggesting that preserving low-frequency hearing during CI can improve auditory rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes and Predictive Factors of Electroacoustic Stimulation Rehabilitation in Children With Limited Low-Frequency Hearing. Nam, GS., Song, MH., Choi, JY., et al.[2020]

In a study involving 20 cochlear implant patients, those with combined electric acoustic stimulation (EAS) showed significant advantages in speech perception when both electrical and acoustic stimulation were used compared to using either stimulation alone.

The EAS group preserved hearing in 9 out of 10 patients post-surgery, while the conventional cochlear implant group lost all residual hearing, highlighting the potential safety and efficacy of EAS in maintaining hearing while improving speech understanding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is electric acoustic stimulation better than conventional cochlear implantation for speech perception in quiet? Adunka, OF., Pillsbury, HC., Adunka, MC., et al.[2022]

The earliest sign of Usher syndrome in patients is delayed walking, with an average onset at 20 months, which is significantly later than the average of 14 months in other congenitally deaf children, indicating a need for early diagnosis.

Cochlear implantation in children with Usher syndrome leads to good speech perception outcomes, especially when performed before the age of 9, highlighting the importance of early intervention for optimizing rehabilitation and speech therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usher syndrome and cochlear implantation. Loundon, N., Marlin, S., Busquet, D., et al.[2019]

In a study of 7356 patients with hearing impairment, only 0.71% were found to be candidates for electric-acoustic stimulation (EAS) implants, compared to 2.52% for standard cochlear implants (CIs).

Among the EAS candidates, only 5.83% (2 individuals) actually received the EAS implant surgery, highlighting the need for healthcare professionals to thoroughly evaluate patients with high-frequency hearing loss for potential EAS eligibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of potential candidates for electric-acoustic stimulation implant in a hearing-impaired population. Saito, K., Fujita, T., Osaki, Y., et al.[2021]

Chronic electrical stimulation of the auditory nerve can lead to significant complications, including surgical trauma and electrode displacement, which may occur at various times after insertion.

Histopathological analysis revealed severe damage, such as loss of hair cells and spiral ganglion cells, as well as new bone growth, highlighting the need for improved design and safety measures in cochlear prostheses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cochlear pathology following chronic electrical stimulation in cats]. Ni, DF.[2007]

Stimulation-Current-Induced Non-Stimulating Electrode Voltage Recordings (SCINSEVs) effectively detect extracochlear electrodes (EEs) in cochlear implants, showing high sensitivity and specificity (91% for CI-A and 100% for CI-B) across different manufacturers' devices.

The study demonstrated that SCINSEVs can generalize to various cochlear implant designs, indicating a promising tool for improving detection of EEs, which can negatively impact speech outcomes in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of Extracochlear Electrodes Using Stimulation-Current- Induced Non-Stimulating Electrode Voltage Recordings With Different Electrode Designs. de Rijk, SR., Hammond-Kenny, A., Tam, YC., et al.[2023]

A new 3D-printed cochlea model with integrated sensing wires allows for better understanding of how electrical stimulation spreads in cochlear implants, which is crucial for improving hearing quality in deaf patients.

The study reveals a trade-off between stimulation amplitude and current focusing across different stimulation modes (monopolar, bipolar, tripolar), providing insights that could enhance clinical strategies for delivering clearer speech signals to cochlear implant users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Instrumented Cochlea Model for the Evaluation of Cochlear Implant Electrical Stimulus Spread. Jiang, C., Singhal, S., Landry, T., et al.[2022]

Optogenetic stimulation using multi-channel optical cochlear implants (oCIs) can provide high spectral selectivity in activating the auditory nerve, which may improve speech recognition in noisy environments compared to traditional electrical cochlear implants (eCIs).

In a study involving adult Mongolian gerbils, the oCIs demonstrated effective tonotopic activation of the auditory pathway with modest power requirements, indicating their potential for restoring hearing in both hearing and deaf subjects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

μLED-based optical cochlear implants for spectrally selective activation of the auditory nerve. Dieter, A., Klein, E., Keppeler, D., et al.[2021]

Cochlear implants provide a significant rehabilitative solution for severely deaf individuals, allowing them to experience sound and communicate effectively, with 7 out of 16 patients achieving excellent results by hearing solely through the implant.

The process includes thorough auditory diagnosis, precise tuning of the implant, and an 8-week hearing training program, demonstrating that even patients with moderate outcomes find substantial benefits from the device, enhancing their daily lives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Auditory achievements of cochlear implantation]. Hildesheimer, M., Muchnik, C., Tenne, S., et al.[2006]

Combined electroacoustic stimulation in residually-hearing ears enhances low-frequency sound perception and expands the dynamic range of hearing compared to pure electrical stimulation alone.

Physiological studies indicate that electrically stimulated hearing ears show less synchronization in evoked activity than deaf ears, which helps reduce hypersynchronization and allows for better integration of acoustic and electric inputs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiological Mechanisms in Combined Electric-Acoustic Stimulation. Sato, M., Baumhoff, P., Tillein, J., et al.[2018]

Cochlear implants are highly effective neural prostheses that can successfully mimic the natural hearing process by electrically stimulating the cochlea in deaf individuals.

Research into how the central auditory system responds to cochlear implants can enhance our understanding of hearing restoration and provide insights into central hearing mechanisms, independent of the cochlea's physical functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cochlear implants: the view from the brain. Middlebrooks, JC., Bierer, JA., Snyder, RL.[2006]

References

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

Cochlear implants: system design, integration, and evaluation. [2022]

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

Outcomes and Predictive Factors of Electroacoustic Stimulation Rehabilitation in Children With Limited Low-Frequency Hearing. [2020]

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

Is electric acoustic stimulation better than conventional cochlear implantation for speech perception in quiet? [2022]

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

Usher syndrome and cochlear implantation. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Prevalence of potential candidates for electric-acoustic stimulation implant in a hearing-impaired population. [2021]

6. China pubmed.ncbi.nlm.nih.gov

[Cochlear pathology following chronic electrical stimulation in cats]. [2007]

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

Usher syndrome: characteristics and outcomes of pediatric cochlear implant recipients. [2013]

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

Detection of Extracochlear Electrodes Using Stimulation-Current- Induced Non-Stimulating Electrode Voltage Recordings With Different Electrode Designs. [2023]

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

Evolution of cochlear implant arrays result in changes in behavioral and physiological responses in children. [2022]

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

An Instrumented Cochlea Model for the Evaluation of Cochlear Implant Electrical Stimulus Spread. [2022]

11. England pubmed.ncbi.nlm.nih.gov

μLED-based optical cochlear implants for spectrally selective activation of the auditory nerve. [2021]

12. Israel pubmed.ncbi.nlm.nih.gov

[Auditory achievements of cochlear implantation]. [2006]

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

Physiological Mechanisms in Combined Electric-Acoustic Stimulation. [2018]

14. England pubmed.ncbi.nlm.nih.gov

Cochlear implants: the view from the brain. [2006]