Investigation of a Device to Deliver Intra-Operative Therapeutic Hypothermia for Hearing Preservation in Cochlear Implantation

Official title

Device to Deliver Intra-Operative Therapeutic Hypothermia for Hearing Preservation in Cochlear Implantation

Overview

The goal of this interventional clinical study is to investigate the use of mild therapeutic hypothermia for preservation of residual hearing in cochlear implant surgery. The main questions the trial aims to answer are: 1. Is mild therapeutic hypothermia safe for use during cochlear implantation? 2. Is mild therapeutic hypothermia effective at preserving residual hearing after cochlear implantation? Participants will receive mild therapeutic hypothermia therapy during cochlear implant surgery. Researchers will compare results from those receiving the therapy to those from a control group (individuals receiving no therapy).

Detailed description

Cochlear implants (CI) have dramatically changed the treatment and prognosis for patients with severe to profound sensorineural hearing loss. With the recent advent of electro-acoustic stimulation (EAS), the combined acoustic amplification at low frequencies with electrical stimulation of high frequency cochlear regions promises to benefit patients with even partial residual hearing by improving difficult listening situations like speech-in-noise and music appreciation. Unfortunately, trauma associated with the implant surgery results in inflammation, mechanical and vascular damage, and loss of remaining sensory hair cells (HC) and neurons. As a result, more than 44% of EAS patients lose residual hearing post-CI surgery and the residual hearing deteriorates by more than 30 dB over time in a majority of patients. This loss of residual hearing post-CI surgery has been the primary barrier for an extended application of CI/EAS.

This clinical trial will evaluate a novel mild therapeutic hypothermia device as an effective therapy to preserve residual hearing post-CI. This system does not require modification of the current surgery or CI devices and will deliver localized, controlled mild hypothermia to the sensitive inner ear structures. With preclinical published results, the investigators have already shown that localized hypothermia during CI surgery is highly effective and safe for residual hearing preservation. Here, the investigators will investigate the implementation of a therapy that benefits patients undergoing CI by improving post-surgical audiological outcomes. Extensive prior commercialization and development experience, intellectual property and engineering expertise coupled with the investigators' collaborators' clinical expertise in Otolaryngology and Audiology will ensure the successful clinical and commercial outcome of this therapy.

Overall, the aim of this clinical trial is:

Validate the clinical applicability, safety and efficacy of the system and device assembly for preservation of residual hearing after CI surgery. The device and hypothermia delivery system will be tested on adult patients undergoing CI surgery at the University of Miami. For clinical translation, the investigators aim to demonstrate that the application of hypothermia combined with the current standard of care for cochlear implantation for residual hearing preservation (steroids) is effective. The investigators hypothesize that the hypothermia application will not negatively impact CI function in patients (safety) and will improve early audiologic outcomes (efficacy) compared to the current standard of care in CI surgeries. The investigators will utilize clinically relevant pre-surgical, intra-operative and post-surgical measures in groups of patients receiving the standard of care and hypothermia therapy.

Preliminary and published preclinical data, and an existing system and device have been constructed for this clinical trial. The proposed therapy and device design for CI surgeries represent a non-pharmaceutical therapeutic strategy to preserve residual hearing.

Interventions

• Device Intra-Ear Canal Cooling Catheter
  Mild therapeutic hypothermia will be applied via the catheter device installed inside the ear canal by an experienced surgeon during cochlear implantation (CI) surgery.

Primary outcome measures

• Pure Tone Audiometry [Time frame: At initial cochlear implant activation or 1 month post-operatively; 3 and 12 months post-operatively]

Secondary outcome measures (2)

• Electrophysiological Impedance [Time frame: Immediately post-operatively/during surgery; at initial cochlear implant activation/1 month post-operatively; 3 and 12 months post-operatively]
• Electrically Evoked Compound Action Potential (ECAP) [Time frame: Immediately post-operatively/during surgery; at initial cochlear implant activation/1 month post-operatively]

Eligibility criteria

Inclusion criteria

Potential participants for the study are patients who have been diagnosed with severe to profound hearing loss (HL) and plan to undergo cochlear implantation (CI) at the University of Miami. The cochlear implant surgery, pre and post-surgical care, and activation and programming of the implant are part of the participants' standard of care. If the inclusion criteria are met (age 18 years and older, equal number of men and women, profound sensorineural hearing loss (for safety study n=6) and residual hearing (see criteria below) from pre-surgical auditory brainstem response (ABR) (for efficacy study n=48), equal numbers of CI devices from all 3 manufactures and English or Spanish speakers the patient will be approached by the study personnel and will be asked to participate in the study.

Exclusion criteria

Subjects under 18 years of age. Subjects not meeting functional hearing requirements.

Types of CI devices:

The study will enroll patients receiving CI devices from all three manufactures.

• Advanced Bionics (FDA indications - severe to profound sensorineural hearing loss (greater than or equal to 70 dB HL)

• HiRes Ultra 3D slim J
• HiRes Ultra 3D midScala
• Cochlear Corporation (FDA indications - moderate to profound sensorineural hearing loss; sentence recognition less than or equal to 50% in the ear to be implanted AND less than or equal to 60% in the contralateral ear

• CI632
• CI622
• CI612
• Med-EL (moderately-severe to severe sensorineural hearing loss (greater than or equal to 65 db HL).

• Synchrony 2 Flex soft
• Synchrony 2 Flex28
• Synchrony 2 Flex 24
• Synchrony 2 Compressed
• Synchrony 2 Medium

Additional patients receiving devices not listed here may be eligible as the criteria by manufacturer change.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Prevention

Study locations

United States · 1 center

• University of Miami — Miami

Publications

• Lotocki G, de Rivero Vaccari JP, Perez ER, Sanchez-Molano J, Furones-Alonso O, Bramlett HM, Dietrich WD. Alterations in blood-brain barrier permeability to large and small molecules and leukocyte accumulation after traumatic brain injury: effects of post-traumatic hypothermia. J Neurotrauma. 2009 Jul;26(7):1123-34. doi: 10.1089/neu.2008.0802. PMID 19558276
• Khan AM, Handzel O, Damian D, Eddington DK, Nadol JB Jr. Effect of cochlear implantation on residual spiral ganglion cell count as determined by comparison with the contralateral nonimplanted inner ear in humans. Ann Otol Rhinol Laryngol. 2005 May;114(5):381-5. doi: 10.1177/000348940511400508. PMID 15966525
• Ye Q, Tillein J, Hartmann R, Gstoettner W, Kiefer J. Application of a corticosteroid (Triamcinolon) protects inner ear function after surgical intervention. Ear Hear. 2007 Jun;28(3):361-9. doi: 10.1097/01.aud.0000261655.30652.62. PMID 17485985
• Perez E, Viziano A, Al-Zaghal Z, Telischi FF, Sangaletti R, Jiang W, Dietrich WD, King C, Hoffer ME, Rajguru SM. Anatomical Correlates and Surgical Considerations for Localized Therapeutic Hypothermia Application in Cochlear Implantation Surgery. Otol Neurotol. 2019 Oct;40(9):1167-1177. doi: 10.1097/MAO.0000000000002373. PMID 31318786
• Kurz M, Lyden P, Lundbye J, Rajguru S. Local to Systemic Use of Hypothermia. Ther Hypothermia Temp Manag. 2018 Mar;8(1):4-8. doi: 10.1089/ther.2018.29041.mjk. Epub 2018 Jan 23. No abstract available. PMID 29360005
• Dugan EA, Bennett C, Tamames I, Dietrich WD, King CS, Prasad A, Rajguru SM. Therapeutic hypothermia reduces cortical inflammation associated with utah array implants. J Neural Eng. 2020 Apr 29;17(2):026035. doi: 10.1088/1741-2552/ab85d2. PMID 32240985
• Bennett C, Samikkannu M, Mohammed F, Dietrich WD, Rajguru SM, Prasad A. Blood brain barrier (BBB)-disruption in intracortical silicon microelectrode implants. Biomaterials. 2018 May;164:1-10. doi: 10.1016/j.biomaterials.2018.02.036. Epub 2018 Feb 20. PMID 29477707
• Bennett C, Mohammed F, Alvarez-Ciara A, Nguyen MA, Dietrich WD, Rajguru SM, Streit WJ, Prasad A. Neuroinflammation, oxidative stress, and blood-brain barrier (BBB) disruption in acute Utah electrode array implants and the effect of deferoxamine as an iron chelator on acute foreign body response. Biomaterials. 2019 Jan;188:144-159. doi: 10.1016/j.biomaterials.2018.09.040. Epub 2018 Oct 18. PMID 30343257

Identifiers

NCT: NCT06375278 · DC019586 · 5R44DC019586

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗