Noninvasive Therapy for Tinnitus

Tinnitus is the perception of sound in the absence of an external stimulus commonly described as ringing in the ears. Tinnitus is a highly common condition, with most individuals experiencing it at some point in their lifetime. At least 1 in 10 US adults experience chronic or disabling tinnitus \[1\] with a significant negative impact on quality of life, often affecting sleep, concentration, mood, and hearing ability. Tinnitus can be intermittent or constant in nature, and intensity can vary or be exacerbated by stress, noise exposure, or other factors. Currently, there is no widely applicable cure for tinnitus, and management typically includes use of sound therapy, mental health counseling, lifestyle modifications, stress management, and distraction techniques, all of which serve to mask symptoms without addressing underlying physiology. Tinnitus is associated with changes in auditory function, with hearing loss being the most associated co-morbidity in patients. However, tinnitus can also be observed in patients with audiometrically normal hearing \[2, 3\].

Tinnitus can have a significant deleterious effect on a person's quality of life, and there is currently no cure. State-of-the art treatment options suffer limitations and are often ineffective and complex. Most widely used tinnitus treatments focus on reducing awareness of tinnitus/masking symptoms and the impact on emotional state rather than seeking to address the underlying mechanisms of the sound generation \[4\]. Treatment modalities include sound therapy using environmental sounds and/or hearing aids, psychological interventions including tinnitus retraining therapy and/or cognitive behavioral therapy, somatosensory stimulation including vagus nerve stimulation and osteopathic manipulation, and distraction exercises including guided breathing and development of new hobbies. Other therapies aim to target the generation of tinnitus, including direct and indirect stimulation of the auditory cortex and/or other brain structures through neuromodulation and pharmacologics \[5\]. Despite the limited success of many of these treatment modalities, none have been shown to be widely applicable to manage tinnitus severity or provide a treatment for tinnitus. Further, systematic reviews have failed to demonstrate a strong evidence base for these approaches \[1\]. Many treatments and strategies currently in research are costly in terms of both time and resources, reducing sufferers' access or their ability to continue treatment over time. For those who do not find relief from their debilitating symptoms, and for those seeking to address secondary effects of tinnitus, there exists a need for novel treatment aimed at reducing acute tinnitus severity \[6\].

The investigators propose to show the efficacy of a highly accessible and translatable, non-invasive device utilizing mild therapeutic hypothermia, or MTH, to reduce tinnitus severity in participants with tinnitus. Unlike other approaches, MTH will address the physiological mechanisms of tinnitus and is easily deployable for routine use and symptom management. With support from a prior SBIR Phase I award, the investigators have designed and manufactured the headband-style device, ReBoundTM, to provide therapeutic hypothermia to the inner ear structures. Modifying temperature of the cochlea is known to influence auditory responses \[7-12\]. The investigators and others have shown that MTH delivered locally or systemically protects hearing function and cochlear structures against noise-induced hearing loss when compared to normothermic animals \[13\]. The present study builds upon strong preliminary and published results of MTH treatment in the inner ear \[14, 15\] and two additional new publications \[16, 17\].

The goal of this interventional clinical study is to establish mild therapeutic hypothermia, delivered non-invasively to the structures of the inner ear, as a safe and repeatable therapeutic method for symptomatic relief of tinnitus. The study will assess both objective and subjective measures to address two main aims:

1. Ascertain the benefits of mild therapeutic hypothermia for symptomatic relief of chronic tinnitus in participants using the ReBound hypothermia device. 2. Ascertain the benefits of mild therapeutic hypothermia for symptom management in chronic tinnitus participants over six months using the ReBound device.

Participants will wear the ReBound hypothermia device for 30 minutes in a single session. Researchers will compare results from those receiving the therapy to those from a control group (sham therapy). Participants will also use the device in-home for 6 months and monitor their symptoms with online surveys.

This research will be highly impactful given the significant adverse effects of tinnitus, an unmet clinical need, on a broad population, and the high translational potential of MTH for reducing tinnitus symptoms.

• Pure Tone Audiometry [Time frame: PTA will be measured in Aim 1 at baseline and immediately after treatment.]
• Distortion Product Otoacoustic Emissions (DPOAE) [Time frame: DPOAE will be measured in Aim 1 at baseline and immediately after treatment.]
• Auditory Brainstem Response (ABR) [Time frame: ABR will be measured in Aim 1 at baseline and immediately after treatment.]
• Tinnitus Pitch & Loudness Matching [Time frame: Tinnitus pitch and loudness matching will be measured in Aim 1 at baseline and immediately after treatment.]
• Tinnitus Functional Index (TFI) [Time frame: TFI will be given to participants in Aim 2. TFI will be administered monthly for 6 months post-baseline.]