New Treatment Options for Tinnitus: Lifestyle, Supplements & Medical Devices

[Dr. Hamid Djalilian]
We first start with the lifestyle dietary modifications. Usually, from what we have looked at in our data, probably somewhere in the 40 to 50% will just improve with just that. They do really have to follow it. As you said, I didn't mention histamine as a dietary trigger and that's what's in nuts, but if they really follow it. Now, it's not too uncommon that people come and they say, "Well, I'm not better, I did everything. I said, "Well, are you drinking caffeine?" "Well, I have my coffee in the morning."

Elimination of caffeine means elimination of caffeine. You can't just say, "Well, I'm just going to drink my coffee. That's okay." Then I'm like, "Well, are you sleeping at a regular schedule?" "I still take naps in the afternoon." That's not good. You got to go stick with the program. I tell them, it's not an a la carte menu. It's a prefix menu. You got to do everything that's on there. You can't get to pick and choose because if you pick and choose, you're not going to get better because we don't know if the ones that you're not choosing are your potential triggers. We have to concentrate on the things.

Now, the ones that we have the most difficulty with are the ones who have a major stressor in their life. Most commonly, it's a spouse or a parent that is ill or a child that they have to take care of. That's a major source of stress that they have to live with every single day. Those are the ones that are most difficult, I should say. The others are untreated sleep apnea. That's why if somebody's not getting better with medication, we will send them for a sleep study. Even if they say that they don't feel they have it, I still will check it just to be sure.

I do use my sleep medicine colleagues a lot for people with insomnia and using cognitive behavioral therapy for insomnia is a very valuable resource. There is a free app that was produced by the VA system called CBTI Coach that people can use. It's an eight-week program, but there are CBTI practitioners all over the country. It would be a good resource for patients to work with. Now, if we do everything, meaning lifestyle changes, dietary changes, get the sleep in order, get medications, usually sometimes a couple of medicines together, we can get about 85 to 90% of them better.

It requires being flexible and sometimes being creative because patients can get side effects. We have to work around them and sometimes combine medicines that we don't traditionally combine. For example, we use a tricyclic antidepressant, for example, like a nortriptyline and they get to a certain dose and they get side effects from that. Then it's too low a dose, I really think they need a little higher dose of something.

I'll add something like Paxil to it, for example, and try to get them the effect that we need sort of the anti-anxiety and anti-migraine effect of that combined together. Then it will add like an anti-seizure to it, like topiramate or gabapentin or lamotrigine, things like that. We have to be creative because patients with migraine are generally very sensitive to medications. Now, I have colleagues who tell me, "Well, I tried lamotrigine and it didn't work, that's all I can do." I tell the patient, "Yes, I know you've tried it, but you got to do the lifestyle and dietary changes and the medication together."

When we actually did a study on, this was on the vestibular migraine side of lifestyle changes and dietary changes plus supplements versus medication. It was just nortriptyline up to 40 milligrams, which is not as high as we generally go, but we just wanted to see a four-week change. They were actually pretty equivalent. When we combined them, they did a lot better. If you don't do one without the other, then you're not going to get the maximum benefit. I really drill down on the diet, the stress reduction, sleep, and then combine that with medicine. Then the medicine we try to direct towards the issues that they have.

If somebody, let's say has the sleep onset issue, I'll give them something that makes them a little sleepy so that they get the benefit out of that part of it so that we can give them better quality sleep. It's really up to, as I said, you have to be somewhat creative sometimes. Some patients we run out of options and we'll use the newer drugs, these anti-CGRP antibodies, even for them. We've had some good benefit from those, although we don't have a lot of patients in that because we generally can get them better with the other meds.

[Dr. Joe Walter Kutz]
That's been a change for us for the past few years. We have excellent APPs in our clinic and they were interested in-- they don't do surgeries. They're interested in medical management, medical ontology. You meet these patients and they're really struggling and you want to help them as best you can, but you know that they're going to need probably follow-up initially maybe every six to eight weeks. You're going to get a lot of messages and it can become overwhelming. Like you say, you can only do so much. I think most practices now have APPs as part of their practice and these are very intelligent, motivated, compassionate individuals.

This has really helped us tremendously. I appreciate you've incorporated that in your practice and I think that's becoming more common. I want to take the last few minutes to talk about some of the emerging treatments, with technology, AI, some of the new bimodal neurostimulation devices. There's some other promising treatments for maybe patients that have continuous tinnitus that are not going to respond to micro treatments. What is your understanding of new treatment options that are coming out for patients?

[Dr. Hamid Djalilian]
Sure. That's a great question. When we started our quest on treating tinnitus or finding a new solution to tinnitus back about 18 years ago at UCI, one of the things I talked about with my colleague Fan-Gang Zeng in our department, he's a hearing scientist was, what's a cochlear implant doing? A cochlear implant is basic to silence tinnitus because cochlear implants work, as you know, about 70% of the time in making tinnitus go away when they're active, of course.

I thought, there are stimulating neurons, because for the audience, when we lose hearing, we're primarily losing hair cells in the cochlea, but the neurons actually stay around for a long time, at least 10 to 15 years afterwards, sometimes longer. They slowly degrade if there's no sound stimulation to the ear, but they will otherwise be maintained if especially there is sound stimulation to the ear. If somebody has some moderate sensorineural hearing loss, they're still getting sound through the ear. Those neurons are going to stay alive for a very long time.

Now, is there a way that we can stimulate those neurons without putting an electrode inside the cochlea, which can cause hearing loss? Our first foray into this was inspired in, so many things, I think, at least in my research has been inspired by a single patient. A single patient says something, and then just suddenly everything gets put into place. I just think this goes along with all these other things that other people have said, and this must be a common theme. Now, this one patient we had had been implanted elsewhere.

He had unilateral deafness and this is before the FDA had approved cochlear implants for unilateral deafness. They implanted him for the purpose of tinnitus. His tinnitus didn't get better with the standard implant programming. They sent the patient to my colleague Fan-Gang Zeng's lab to try to figure out if there's a way that we can actually make the tinnitus go away. First, we had a couple of PhD students who have spent months with him. He would come down from Northern California every couple of weeks or so and spend a couple of days with us. They found actually at a very low stimulation rate that usually an implant can't do.

They used a research interface that they could actually make the tinnitus go away completely in him. They published some very nice studies with electrophysiology when this tinnitus was silenced and when it was active. It was actually pretty cool. Then that made us think, could we target these neurons with sound because if people still have hearing, we may be able to target the neurons? That then actually started the process where my colleague Fan-Gang Zeng developed a device called SoundCure at the time. This was a device that was dispensed by audiologists but unfortunately is now not on the market.

I at the time thought, can we figure this out remotely for people? Because we found this stimulus around the frequency of the tinnitus is what helps the most. We then developed a software that was web-based. People could connect, could match their tinnitus, and we showed that was just as accurate as doing it in an office. Then we actually did a rough test of hearing online, which was actually the first time that had been done. What we realized is we don't have to have calibration. We just need to know relatively, what's their low frequency, what's their high frequency, what's their mid-frequency range approximately, and their relationships to each other rather than the actual sound level.

Then the software actually create a sound therapy where it would give them certain sound around the frequency of the tinnitus, but it was a narrow band noise. It wasn't as harsh as the tinnitus sound. Just a background for audience. If somebody has a tinnitus at, let's say, 8,000 Hertz, you give them 8,000 Hertz sound to hear, that will temporarily make their tinnitus go away in most of the people who have tinnitus. Let's say at that frequency, for example. That obviously doesn't make any sense to listen to the same sound that they're hearing internally.

We then widened the frequency band a little bit around it, and then we gave them another couple other frequency bands that made it so that makes it sound more like white noise. Those frequency bands were actually mathematically related because the way that the auditory cortex is organized is the neurons for 8,000 Hertz are right next to the 4,000 Hertz, which are next to the 2,000, et cetera. Every octave you come down, every half of that number, those cells are right next to each other. We then gave them these sounds and we found that actually that worked better than generic sound when we did a clinical trial that we did a randomized crossover design.

Then after a while, just again, seeing a lot of patients with tinnitus, I thought, this isn't solving the problem. I know we can reduce the volume, we can reduce the impact, but we're not solving the problem. These people have a lot of stress-related stuff and whatnot. We actually developed an internet-based cognitive behavioral therapy for these people. We did a trial of that, that was actually very effective. Then we actually did a trial combining cognitive behavioral therapy online and sound therapy online, customized sound therapy. That actually had a pretty big effect.

Actually, the effect of that is similar to some of the new emerging devices that are on the market currently in terms of reducing the tinnitus functional index and the volume and whatnot but in this interim, I realized that migraine is a big process that's related to tinnitus. Then we actually incorporated the migraine education into our cognitive behavioral therapy so that people can get that information through that. Then I was still hungry for a cure because I thought we're making the volume a little bit better, but we're not curing it. We need to find a cure.

We actually, back in 2006, when I started at UC Irvine, when I got the IRB approval for our sound therapy studies, I actually also included electric stimulation of the cochlea because I thought that we should be able to make that work somehow. Now it took some time and collaboration with my hearing scientist colleague and my neurotology colleague, Harrison Lin, and we were able to design the study using the ying-ling electrode that we use in surgery for facial nerve stimulation in scoliosis cases that has a very small ball electrode. What we did is we actually made an incision in the tympanic membrane and passed the electrode into the round window and stimulated the round window directly.

We found that actually we can make the tinnitus completely silent in patients, not everyone, of course, but majority of patients, but at a level where most of the time these patients either did not hear the electric stimulation, meaning they didn't hear a sound from it, or they habituated to the sound from the stimulus because the stimulus, of course, is going to go through neurons, so it's going to generate a little bit of sound. They tended to habituate to that, but then the tinnitus also came down. We had one patient who had several hours of residual inhibition.

This is a patient who had 20 years of tinnitus at a shadow 60 dB hearing loss, and we can make your tinnitus go away for several hours with just a five-minute stimulation. We thought, "Okay, this is what we should be focusing on. How can we get a device into the middle ear that could do this?" The challenge is always, whenever I've thought about devices for the ear, I always have thought, "I want to make this a device that all otolaryngologists can place, not something that just otologists can place." Because, again, you're going to reach that bottleneck of only 300 people who can do the surgery in the country, and then, you have, again, millions of people who could benefit from this.
We went a little bit a different route than traditional devices, which are implanted under the skin and have an electrode that go into the middle ear. Our device actually is all contained in the middle ear, and there's an ear canal component that charges it up, so there's no implanted battery. In the same system that a coil from a cochlear implant can do the power transfer, this does a power transfer using a very tiny coil.

Now, towards the end of the design and fabrication of the internal implant, which would be in the middle ear, which is basically a receiver and some custom-designed chips that then take the signal, translate it into an electric signal, and then can translate, put that into the round window. Then there's an ear canal component that's sending the signal and the power, and then there's a handheld component that the patient will use for settings and/or can be programmed by the audiologist or whoever. That's something we're doing.

Now, in parallel, I know that a colleague that you and I both know and love, Matt Carlson at Mayo Clinic, is also doing a similar thing, but his device is implanted under the skin and goes on to the promontory of the cochlea and stimulates the cochlea as well. They are in, actually, human trials. I don't know how many patients they've done so far, but that holds promise as well. It's using the similar ideas, what we do. It's just ours is going to be, hopefully, something that any otolaryngologist can place without the need to do facial recess and things like that.

[Dr. Joe Walter Kutz]
Yes, that's great to have, something that the transcranial magnetic treatment, it would work, but then once you would stop the therapy, a lot of times it wasn't lasting. Something like this would be something you can continually do. With your device, you just raise a temponomatal flap and place the device in and put the flap back down. A pretty straightforward operation.

[Dr. Hamid Djalilian]
That is correct. Yes, exactly. That's the hope and goal. We've been able to keep the device at a pretty small dimension. There isn't a lot of room in the middle ear, as you know, especially the malleus. Between the malleus and the promontory is only about two and a half millimeters. Inferiorly, there's more space, of course, and so our device is going to fit within the confines of the middle ear, the way it's currently designed and fabricated.

[Dr. Joe Walter Kutz]
Great. Have you had any experience with the Lenire device? We're not part of their initial release yet, so I don't have a lot of experience. I do have patients calling. Can you tell us about your experience with the Lenire device?

[Dr. Hamid Djalilian]
Yes, so Lenire, and I know the founder, Hubert Lim, is an incredibly intelligent researcher, and we actually really tried very hard to recruit him to come to UCI. Anyway, so that device, I think it's a great idea. I think there are probably a small subset of patients that do get benefit from it. I'm a little bit biased because I see all the failures, of course, so all the patients I see are the ones who didn't get benefit. The ones who do get benefit, they don't necessarily come to see me.

Now, I think considering that we know now, at least our understanding of what makes tinnitus loud is really the central sensitivity phenomenon that migraine creates that causes the brain to pay attention to that signal. That is not really addressed with a device like the Lenire. Now, the Lenire device is sending some trigeminal stimulation, in effect, by stimulating the tongue? I don't know if that stimulation is enough to have an effect. The tongue was primarily chosen based on the animal experiments that were done initially, but I don't know how much of the effect is from people sitting quietly for 30 minutes twice a day and not doing anything other than just relaxing.

I think if you have a lot of patients with tinnitus, just listen to, let's say, just sound therapy and relax for an hour a day, that would have a pretty significant effect on their tinnitus as well. How much of that is more than the sound and relaxation, I don't really know. I would have liked to have seen the trials be done a little bit differently with maybe a paddle that doesn't stimulate, so patients are doing exactly the same thing, and maybe using just a generic sound, like white noise.

That's not for me to decide how their trials should be done, but as far as does it have an effect, I think there are some people who do get benefit. How much of that benefit is from one component versus the other, I don't know. I think just knowing Dr. Lim, he's such an incredibly intelligent person, he's working on other devices as well, so I think that may not be necessary. Their final device or maybe newer iterations that potentially may be more effective. We currently don't offer it either, partly because we're just so successful with what we're doing for the fluctuating tinnitus patients and the ones who have changed levels, but at the same time, we do use customized sound therapy.

It's a lot more affordable than the device, which tends to be somewhat expensive. Do we use sound therapy, yes. Do we use hearing aids? Yes. If someone has significant hearing loss, using hearing aids is going to be a benefit to them because the more sound you get to the brain, the quieter the brain cells are going to be, and so therefore, the tinnitus is going to be quieter. Of course, hearing aids can't help when there's no sound around, so that's why they need some sound therapy, so we combine them usually together.