Deep Brain Stimulation (DBS) for Tinnitus

Thank you! I will try to write them an email!

 

Hey, Ela. Did they respond to your email?

Anyways, I haven't followed Tinnitus Talk long enough; do you have any expectations when DBS will be available for tinnitus?

 

I thought I'd do a brief recap on the state of deep brain stimulation trials as of June 2022:

There are two trials going on in Europe, one from Maastricht University in the Netherlands, and one from the University Hospital in Grenoble, France. No data is available yet, and it is unclear to me what phase these trials are on.

There has also been a Phase 1 trial in the U.S., completed in 2019. Here's the article that describes the trial. Although the procedure is extremely invasive, it appeared to be relatively safe, with no adverse events reported (except for one patient, but that was apparently unrelated to the procedure), and reasonably effective. I haven't found any more information regarding a phase II of this study so I am assuming it is in limbo, but I'll reach out to the investigators to learn more.

Whether DBS simply treats the distress caused by tinnitus or actually lowers tinnitus volume is unclear. I've read conflicting anecdotal reports in this form (one was a secondhand account from a participant of the Maastricht trial, and the other was a firsthand report from a participant of the U.S. study).

Here's something I've been thinking: I remember that there was a paper on non-invasive deep brain stimulation that made some big waves in 2017. It seems the technology is promising but needs some fine-tuning (I found a 2020 paper that suggests improvements on the tech). I find this approach fascinating, but it seems so far no one has tried to use it to treat tinnitus. I wonder why. I think I know a researcher I can ask this question to; I'll post their response here if I hear back.

 

The trial at the Maastricht University doesn't accept patients outside of the Netherlands. The trial at Grenoble doesn't accept patients outside of France.

I really don't know when it would be available. They are only running trials at the moment.

The data I had from the Maastricht University trial was from an earlier point of the trial, I have no further results or information on how the trial progressed.

The trial in France says on their page that it is still recruiting, so did the trial start or not?

The person participating in the U.S. trial never said if his tinnitus went away. Actually at one point he says he doesn't have data about the other participants, if their tinnitus went away, which makes me think that his tinnitus did go away!

They are recruiting again this summer in the U.S., I saw the same doctor in the new trial.

New Tinnitus Research Focused on Neural Networks Shows Promise for Precision Treatment

I assume you have to be in the U.S. for this one?

Also the articles you have posted, they don't have any clear conclusions in terms of did they help patients with tinnitus or not?

And there is this big thing with noise sensitivity. You can't have noise sensitivity but you can still have reactivity to noise when you have tinnitus. Most people with tinnitus wear hearing protection in noisy situations so where can the line be drawn, who can qualify for these trials in terms of how your tinnitus would react to noises? Because some or most of this reactivity is related to central gain and the maladaptative connections created in the brain due to tinnitus (dysfunctional auditory nerve), which I'm thinking the DBS surgery will correct? At least to a degree where you feel a great reduction in your tinnitus.

We need more answers.

 

He did say this:

If you mean that he never said if his tinnitus went away eventually, years after the treatment, then yeah, you're right, he hasn't (and he's no longer active here).

Great find! Thanks so much for sharing. So it seems they are trying to really zero in on precisely which regions of the brain are involved in tinnitus for each patient. It seems like the right call, hopefully it leads to more effective DBS treatments. And yeah, I'd assume you would have to be in the U.S. for the trial.

Kind of, but let's dig a little deeper into that article from the U.S trial because the results are interesting.

60% of participants from the U.S. trial showed "clinically significant improvement". How did they measure this, and what does it mean? For their primary outcome, they used the Tinnitus Functional Index (TFI), which is basically a survey in which you describe how tinnitus impacts your daily life. They also asked participants to describe the loudness of their tinnitus on a scale of 0 to 10 before and after the treatment; this was used as one of their secondary outcomes. For both of these outcomes though, the effect sizes were huge. The mean decrease in TFI scores was 23.3, but that ranged from a participant who only had a 2.4 decrease to a participant that had a whopping 70.4 point decrease (their TFI went from 75.6 to 5.2. Imagine that). Nevertheless, of the five participants, three (60%) had a TFI decrease of over 13 points, which is how they define clinically significant improvement. Tinnitus loudness reduction followed a similar pattern: the mean reduction was 2.5, but that ranged from a participant reporting a 7.8 point improvement to a participant reporting 0 change (most other participants reported an improvement of around 1.5 points. Remember these points are on a scale of 0-10, not in dB).

To summarize, they had a super responder for whom DBS basically cured their tinnitus. There were other two participants who improved, but to a lesser degree, and two participants who didn't. Worth noting that this was a Phase 1 study, so the real focus was on safety rather than effectiveness. It seems that they are now trying to figure out why some people responded so well and why some didn't. Which is great, but sadly it means that a phase II of the study really is in limbo (if it even happens at all).

 

New DBS technology:

World’s smallest Deep Brain Stimulation (DBS) device on trial at North Bristol NHS Trust

 

This is in England, isn't it? Could they use the same technology for tinnitus? How do you send the necessary voltage into the brain? Using the remote upon your brain where the the battery is together with the electrode?

 

Did you find any results for the first clinical trial? I don't see it on the link you posted!

What do you understand by chronic and stable tinnitus? Does this mean fluctuations in tinnitus due to noise is an exclusion criterion?

 

I understand tinnitus being chronic if you have had it for more than 3-6+ months. But I honestly can't answer what "stable" means because mine fluctuates a lot so I'm not quite sure about this.

I also found Dr. Dirk De Ridder's Tinnitus Talk Podcast very insightful.

Tinnitus, Ingrained in the Brain? - Prof. Dirk De Ridder

Lots and lots of idiots (especially GPs) tell you tinnitus is Ingrained or burnt in your brain lol, what obviously makes no sense if DBS works, the brain just seems to be in a waggy state, especially the thalamus where information is filtered out and yeah, I have to agree on the concept of thalamocortical dysrhythmia, from that perspective all makes sense and especially the mechanisms of DBS.

Surgical Neuromodulation of Tinnitus: A Review of Current Therapies and Future Applications

 

I contacted the team from Grenoble.

They said it takes much more time than expected, for now they have operated only 1 patient.

I may take the risk to be a guinea pig (if my very recent hyperacusis increase subsides..)

I need to contact an ENT from their hospital before setting an appointment in September with the neurologist in charge of the project (as an anecdote, it appears to be the same guy who first operated Michael Schumacher after his ski accident, which tends to scare me even if after some research he apparently did a good job on him but he was way too damaged).

 

God, so they gave no timeframe when the trial will finish? As I understand it, they don't take this treatment off label until they finish the trial and see the results? I'm not from France, so I can't get in. Also, my tinnitus is reactive to more sound. I keep seeing them state that they only accept stable tinnitus for the trials?

Mine is sort of sensory tinnitus, more so related to the brainstem (or starting from there) than the ear. So logically it would be reactive. In my mind the voltage of the DBS implant will regulate impulses and the reactivity would go away.

 

Yeah it's just an evaluation, they are sadly far from "off label" treatment for now.

They don't mention reactive tinnitus as a criteria:

Inclusion Criteria:

• Between 18 and 75 years old,
• Uni or bilateral permanent non-pulsatile tinnitus, without associated vestibular pathology, with or without hearing loss,
• Severe tinnitus resistant to treatment failure,
• Tinnitus intensity on the Visual Analog Scale (VAS) ≥ 7,
• Presenting a quality of life score on the Tinnitus Handicap Inventory (THI) questionnaire> 76 (= grade 5),
• Social security affiliates or beneficiaries of such a scheme
• Informed and written consent signed by the patient.

Exclusion Criteria:

• Vestibular dysfunction (balance disorder),
• Epilepsy,
• Intercurrent serious pathology,
• Brain tumor,
• Contraindication to surgery or anesthesia,
• History of cerebral infection with herpesvirus,
• With a contraindication to the practice of MRI, MEG, Computerized Tomography (CT) scan,
• Under anticoagulants and antiaggregants (Anti vitamin K, low molecular weight heparin, aspirin and derivatives, clopidogrel antiplatelet agents and assimilated, new oral anticoagulants (NACO)) for which a therapeutic window can not be opened within 3 months before and after the surgery,
• Included in another therapeutic protocol,
• Progressive dementia or psychiatric illness,
• Presenting a suicidal risk deemed important for less than 3 months (Montgomery and Asberg depression scale (MADRS): suicidality item (item 10) score> 2),
• Enforced hospitalisation,
• Pregnant, parturient or breastfeeding, lack of contraception in patients with the capacity to procreate,
• Subject to a legal protection measure,
• Deprived of liberty by judicial or administrative decision,
• Isolated patient without any contact in case of emergency.

 

I really don't understand why they go so slowly...

 

Well, I'm more confident on the trial in Maastricht and in the US by Dr. Cheung (Phase 2).

If we're lucky, we'll have some decent results by end/beginning of next year in PubMed. For universal use, I'd expect at least 5-10 years, sadly. I mean, I don't know, it's not something I can go for and ask lol... (yet).

 

Is Dr. Cheung doing a Phase 2? I tried to research that before and couldn’t find it.

 

So far they have completed Phase 1 and will start Phase 2 soon from what I got told. They have published a report about further work at UCSF. They will investigate it further until they reach Phase 3 and FDA approval. Probably anywhere in early 2030s.

New Tinnitus Research Focused on Neural Networks Shows Promise for Precision Treatment

 

I actually met Dr. Cheung recently to get his advice on my particular tinnitus symptoms. I didn't realize at the time that this is the research that he's involved with. He didn't mention his research when I met him. I want a follow-up appointment, but he's booked out for months.

 

If you have a chance to meet him again, please ask him about this treatment. I would honestly consider this but got no timeline whatsoever. I would really want to know his plans with it and his timeline.

 

I'll see what I can find out. I'll be booking an appointment soon, and his staff is who I speak with when i book, but I'll see if there's a way I can send a message along to him.

 

I don't think you can get in the trials unless you are from the United States.

 

That would be awesome. I just hope he can give some information about when it will be available for severe tinnitus, and what are his expectations. I would, like I said before go for it right away if I knew it can eliminate tinnitus, and surprisingly it can

It's a shame that it's not available and so many good people are still suffering. It ccould make such a difference, I think, if someone is having suicidal thoughts (for example). He'd rather go for DBS and silence instead of despair...

 

Can I ask why? DBS was invented in Grenoble so I would tend to think they have more experience with this stuff, no?

I don't have your science knowledge though.

 

Grenoble just had their first DBS clinical trial for tinnitus, no? They have done DBS for tinnitus in the United States since 2017.

 

They also investigated other settings and stimulation patterns, e.g., one trial targets the medial geniculate body whilst the other targets the caudate nucleus. And as mentioned, they already completed Phase 1 and enroll for Phase 2 soon so they are major steps ahead and they are basing their work on precise neuroimaging e.g., the UCSF and Maastricht.

 

5 years later, and we only have 1 clinical trial of 6 patients of which 4 show improvements. That's it?

 

Trial one was completed:

Pilot Study of Deep Brain Stimulation (DBS) in Area LC for Chronic Tinnitus

I heard Phase 2 is starting soon.

The Maastricht trial is concluding in December this year:

Deep Brain Stimulation for Tinnitus

 

Unless they are late too!

 

They really are. The website is not updated at all. I just wrote an email to them. They are far from finishing. More than this, they suggested me to have DBS for depression to alleviate tinnitus.

What kind of answer is this?

 

How can you get in touch with the Academic Medical Center (AMC) in Amsterdam, Dr. Dijkstra?

 

I don't know if she's still working at the AMC. But you can find her email address on:
https://brainclinics.com/eva/

Good luck!