Bimodal stimulation means providing two different modes of stimulation. Various groups of researchers are working on different bimodal stimulation treatments for tinnitus. One of these groups is Dr. Susan Shore and her team at the University of Michigan. Auricle, Inc. is the licensee of the intellectual property developed by Dr. Shore’s Lab.

The device that Dr. Shore created provides sound stimulation to the ear combined with mild electrical stimulation of the neck or jaw. This treatment is based on many years of basic science studies that demonstrate that tinnitus originates in the first brain region that connects to the ear, the cochlear nucleus. The cochlear nucleus is where sound signals and somatosensory (touch) signals come together. The precisely timed auditory-somatosensory stimulation provided by Shore’s treatment has been shown to significantly reduce the spontaneous firing rates of neurons that carry the tinnitus signals to higher regions of the brain, thus inhibiting the perception of tinnitus in those higher brain regions.

The take-home treatment device was used for 30 minutes per day for 6 weeks in the latest human trial. Each device provided a bimodal stimulation treatment in which the auditory stimulus was matched to the patient’s tinnitus sound and the electrical stimulation was adjusted to the threshold of sensation. You can read Dr. Shore’s latest published paper to understand more. The paper provides the full results of Dr. Shore’s clinical trial in which her team tested the treatment on 99 participants. The results showed statistically significant reductions in tinnitus loudness and impact on life.

I am not in a position to discuss or otherwise confirm or deny anything concerning Auricle and the FDA. The company is certainly working on a regulatory clearance, but it is not making public comments concerning the process. The company has provided the following general statement. 

Auricle, Inc., the privately-held company that is the exclusive licensee of the patents related to The Shore Lab’s tinnitus therapy, is engaging with the FDA concerning a regulatory clearance. The Company is not, however, providing guidance or other information concerning the status of its engagement. It is not appropriate for companies in the midst of negotiations with the FDA to forecast or otherwise publicly speculate on the terms and conditions that may lead to a clearance—this can cause potential issues with the agency as well as set potentially inappropriate expectations with other stakeholders and interested parties. In this same vein, the company is not providing commentary about agency guidance and the specific terms and conditions that would lead to a clearance.

Auricle thanks the Polish Tinnitus Association for their interest and desire to provide assistance, but at this time the Company is focused on an FDA clearance. Europe is an important market for the Company, but the European Union’s updated Medical Device Regulations reveal that the pathway to clearance is neither simple nor fast relative to the United States. For certain, the Company will focus resources on an EU clearance in the future.

As a privately held company, Auricle is raising the resources based on its business plan and milestone objectives. It is not providing public guidance on questions pertaining to commercialization.

Outside of the engagement with the FDA, there are no on-going collaborations with any other governmental division or entity.

Auricle has no immediate plans for a website.

The device needs to be fitted for each patient by a trained healthcare professional (for example, an audiologist). Patients are expected to have some level of follow-up to monitor results, and there are no adjustments made by the patient directly.

Auricle is not providing commentary concerning the sequencing of global markets.

Auricle is not providing commentary concerning pricing, but it is the company’s hope to make the therapy available to as many tinnitus sufferers as possible at pricing that is accessible to most.

Whether or not insurance providers offer therapy coverage will be dependent on the individual provider. In the US, because there is no established standard of care for tinnitus treatment and therefore no CPT (‘Current Procedural Therapy’) codes for reimbursement, it will require a multi-year effort for providers to offer reimbursement. There are many established and possible financing models, however, that should contribute to making the therapy accessible to most.

The terms and conditions for ‘compassionate care use’ per the FDA are extremely specific, and it is only granted for immediately life-threatening diseases where there are no cleared therapies. There is now at least one FDA-cleared device to treat the symptoms of tinnitus, so compassionate care use of other non-FDA cleared approaches is challenging. In addition, Auricle does not have manufactured devices and the requisite infrastructure to support device use outside of investigational research.

A majority of people with tinnitus can modulate. These modulations reflect the connections between the somatosensory and auditory systems. In those who cannot modulate, we assume those connections are still there but perhaps not as strong. The preclinical (animal model) studies indicate that projections from somatosensory centers to the cochlear nucleus are present in 100% of animals tested.

It is not possible to make this connection as the basic science studies were done on the auditory system and not the visual system. The circuitry of the two sensory systems is different so a new set of studies would need to be done to investigate visual snow and a comparable visual based treatment.

Residual inhibition is a real phenomenon that occurs in many subjects. We did not specifically study the effect of residual inhibition on auditory-somatosensory integration. It is unlikely that residual inhibition plays a role in our bisensory treatment because the long term suppression that we see with specific auditory-somatosensory orders and intervals is based on long term plasticity in fusiform cells of the cochlear nucleus, a process that is independent of residual inhibition.

All signals must be processed by the cochlear nucleus (including the dorsal cochlear nucleus) before ascending to the rest of the auditory system. Thus, the tinnitus signal that fusiform cells produce is passed along to the rest of the brain. So yes, the tinnitus signal originates in the cochlear nucleus. More central centers may modify the signal that they receive from the cochlear nucleus, including descending pathways.

We don’t know that the guinea pigs had somatic tinnitus per se. We do know that somatosensory stimulation could modify auditory signals in all of the guinea pigs. Thus, we chose those who could modulate their tinnitus as our first test group as this was the group showing evidence of somatosensory innervation to the auditory system.

Our studies have shown no influence of tinnitus duration on treatment efficacy.

The age of the patient per se did not influence the outcome of the studies.

The TinnTester interactive tinnitus matching software program is designed to match different kinds of tinnitus and has shown high test-retest reliability. Most tinnitus is narrow band or wide band, meaning it is comprised of multiple frequencies – called the tinnitus spectrum. We matched the tinnitus spectrum and presented this as the sound part of the bisensory stimulus. We did not see differences based on spectrum.

We did not assess typewriter tinnitus – this would need to be assessed In the future.

We did not assess pulsatile tinnitus – this was an exclusion criterion as pulsatile tinnitus can be linked to cardiovascular system, so may have a different etiology to other types of tinnitus.

The majority of patients did not report hyperacusis.

We did not assess this type of tinnitus.

At present, bilateral severe to profound hearing loss would preclude use of the device as the signal needs to be heard to be effective. The study only included up to moderate hearing loss.

Yes as long as the sound can be heard in one ear this can likely still be effective.

We excluded subjects who had used a hearing aid in the 6 months preceding trial enrollment so that any potential treatment impact would be eliminated. But there is no reason why hearing aid use would be a contra-indication provided that the patient’s hearing loss threshold is within our prescribed range.

We do not know this at this time. Research would have to explore this paradigm.

It is possible that the treatment could help those who cannot modulate because the preclinical (animal) studies show that after cochlear damage, all animals show somatosensory reinnervation of the cochlear nucleus. We have not yet tested those subjects.

Our inclusion criteria for our studies only specified constant, bothersome tinnitus, not what caused the tinnitus. Since the most frequent factor associated with tinnitus is hearing loss due to noise over exposure (including hidden hearing loss), many of our patients had noise induced hearing loss (or hidden hearing loss). Meniere’s disease was excluded from our study because tinnitus in Meniere’s disease patients is intermittent.

It is likely that even patients with somatosensory involvement in their tinnitus also have some degree of cochlear damage, so resolving the TMD may not be necessary for the treatment to work.

One person had minor redness on their skin due to repeated tape use without sufficient electrode gel. This went away when instructions were followed.

The device is intended for tinnitus patients that are able to modulate their tinnitus with a somatic maneuver. They also must be able to hear the auditory stimulus, so persons with mild to moderate hearing loss will generally be fine (severe hearing loss patients may be contraindicated). We excluded patients in the trial who had Meniere’s Disease, acoustic neuromas, and some other specific conditions. Patients with these conditions may not be suitable for our device.

Only one patient experienced tinnitus worsening possibly associated with using the device during active treatment. Other instances of worsening were related to noise overexposure events during the trial (eg. attending a rock concert).

These returned to within one std. deviation of baseline.

It will probably be ok but safety testing will have to be done for these specific cases.

No, our device has hardware and software limits to prevent over stimulation.

The reason for this was that we derived the treatment from the preclinical studies in which we damaged only one ear and then treated that side. But we found in the humans that treating one side reduced tinnitus perceived in both ears. The reason for this is because there are neural pathways between the two cochlear nuclei, where the tinnitus is generated and where the treatment site of action occurs.

The treatment should only be used as prescribed, with the earphone inserted. However, the level of the sound can be adjusted to be comfortable for each person, as was done in the trials.

The subjects were told to sit in a quiet room while they were using the device (only 30 min per day). They were not told to concentrate on the treatment.

The sound and the electrical stimulation are equally important. It is in fact the combination of the sound with the electrical stimulation in a precise order and time interval that produces the long-term depression that reduces the tinnitus. The precise timing was derived from the preclinical studies in which we recorded from fusiform cells to discover which timing and order would produced the most long term depression.

It is possible that longer times than 6 weeks may be even more effective.

A crossover study is the strongest possible design for a clinical trial, but only if there is recovery (or return to baseline) after the first treatment period during the washout phase. This worked well for the first pilot study with 4 weeks of treatment (Marks et al, 2018). For that study, the majority of subjects’ tinnitus had mostly returned to baseline after the 4 week washout. For the second study we used 6 weeks of treatment and 6 weeks of washout before the crossover as we expected that we would see a return to baseline after 6 weeks of washout. We did not expect that the treatment would work so well after 6 weeks that there was no return to baseline during the washout. What we saw was that the treatment after 6 weeks was so long lasting that we did not see recovery. In fact, we saw a continued treatment effect up to 12 weeks (and beyond). For that reason the crossover did not work for the second study. This is called a “crossover effect” and it means that the second treatment period was biased by the first period. When that happens, it is not statistically valid to analyze the second half of the study. That is why we focused our analysis only on the first period.

TinnTester is a software suite designed by Larry Roberts to measure psychophysical attributes of tinnitus including loudness and likeness at several frequencies. The TinnTester reports loudness measurements in dB SPL which can also be expressed as sensation level (SL) by comparing to the audiogram. There have been a number of studies showing test-retest reliability.

Prior to using the device subjects were tested to find out their electrical stimulation thresholds. The stimulation level was then set to just above the threshold, which was barely detectible or perceptible. We didn’t have an objective test for detection. We interpreted subject statements that they could not tell which treatment they were getting to be evidence that they had habituated to (or become accustomed to) the electrical stimulus. Keep in mind that the electrodes were in place for the active and sham treatments and the tape itself produced some sensation, likely helping with the blinding.

In reviewing the literature, we found many papers using different thresholds of meaningful change for the THI.

We utilized Adamchic et al, 2012, who provided their calculation methodology:

https://link.springer.com/article/10.1186/1477-7525-10-79

It is important to compare a subject’s tinnitus with their own baseline as we want to see if their tinnitus got better. We compared both the active and sham treatments with the subject’s baseline at the beginning of the treatment.

We were limited in the number of figures that we could include. Mean change for THI at 6 weeks (PP) is -9 for active -2 for sham. For ITT -7 for active and -2 for sham.

This appears to be a mislabelling in the paper. The 14.1 value actually refers to the TFI, while the loudness should be -10.9, consistent with the text and figures.

As explained above in the question about a cross-over study, I’ll provide the same explanation again.

A crossover study is the strongest possible design for a clinical trial, but only if there is recovery (or return to baseline) after the first treatment period during the washout phase. This worked well for the first pilot study with 4 weeks of treatment (Marks et al, 2018). For that study, the majority of subjects’ tinnitus had mostly returned to baseline after the 4 week washout. For the second study we used 6 weeks of treatment and 6 weeks of washout before the crossover as we expected that we would see a return to baseline after 6 weeks of washout. We did not expect that the treatment would work so well after 6 weeks that there was no return to baseline during the washout. What we saw was that the treatment after 6 weeks was so long lasting that we did not see recovery. In fact, we saw a continued treatment effect up to 12 weeks (and beyond). For that reason the crossover did not work for the second study. This is called a “crossover effect” and it means that the second treatment period was biased by the first period. When that happens, it is not statistically valid to analyze the second half of the study. That is why we focused our analysis only on the first period.

Yes, half as loud for every 6 dB decrease. So, -6 dB is perceived as 50% less loud, and -12 dB is perceived as 75% less loud.

Yes, subjects did show a lowering of the primary pitch of their tinnitus during the active treatment but not the sham treatment (see Marks et al, 2018).

The TFI reduction was not modest, and was as much as 18 points lower than baseline TFI score at the 12 week time point. This is greater than the minimum value for clinical significance, and we saw that TFI reduction moved in parallel with reductions in tinnitus loudness.

Yes, subjects have asked if they could buy the device even for high cost.

There will be real-world studies once the device is marketed.

I was born in Johannesburg, South Africa. My first degree was in speech pathology and audiology. I practised for a few years before going back to school to get a master’s degree and then Ph.D. in physiology, with the aim to study the brain. I spent many years studying the anatomy and physiology of the cochlear nucleus and other central structures. Major discoveries from my lab included documenting the structure and function of somatosensory innervation to the auditory system and how it changed after cochlear damage. These studies led to the study of tinnitus circuitry.

I don’t think anyone experiences true silence. The goal to to return to a state in which people can function well.

I am a co-founder and the chief scientific officer of Auricle. The company was started to commercialize the treatment developed in my lab. The other co founders are Jonathan Pearson (the CEO), under whose expert guidance we are working towards an FDA approval, and David Martel, a former bioengineering student in my lab and co-inventor of the treatment.

Since I am now retired to Professor emerita status, I am no longer lecturing at the university. But I am continuing research activities with some of my colleagues at the University of Michigan. This does not impact my work at Auricle.

I have very mild tinnitus that is not bothersome. I served as a subject to help develop the TinnTester application in the lab but have not tried the device myself – this would really be a conflict of interest.

I do not generally participate in social media forums.

I am too busy answering questions. 😄

My permission is not required.