New University of Michigan Tinnitus Discovery — Signal Timing

[Damocles]

It's time to kick TRT, CBT and positive thinking to the curb and make way for treatment that actually lowers tinnitus volume!

 

[Kain]

The study is out!

 

[dipp]

Greatest achievement to date. This is amazing. Unfortunately, since my recent worsening, it doesn't seem like if I'm going to see this released to the market. Anyway, congratulations on this.

 

[eagerUser]

View attachment 54972

Well, it's another thought based treatment because you have to think about Dr. Shore consciously, otherwise you won't see any benefits

 

[@dam]

Almost there!!! Can anyone tell what % of those treated had a significant clinical response? I'm ready to believe but I want to be realistic as to my chances.

EDIT:

Just found it on a chart, ~65%.

Eh, not the nicest feeling. However, I wonder if the remaining 35% could have benefited had they done more weeks of treatment? I don't see how it's impossible to think that their brains were adapting a bit slower.

 

[InNeedOfHelp]

Some findings:

- People with more somatic tinnitus modulation movements benefited better, but it's stated that non-somatic tinnitus should also benefit.

- 7 people had worsened tinnitus during treatment (related/non-related), too little detail provided on adverse events. Subjects were removed from the study if their tinnitus loudness and TFI increased significantly for two consecutive weeks.

- Baseline was 5-10 years of tinnitus.

- Baseline TFI was around 40-45.

- Baseline loudness around 55 dB. Wow? This does not correlate to TFI and seems massive, I would be surprised if this was correct.

- Reduction of approximately 10 dB in tinnitus loudness.

- Non-responders not defined. Huge miss.

- Nothing on hyperacusis.

- Nothing on people who worsened (characteristics).

- Nothing on type of tinnitus (multi tonal etc) and how tinnitus was acquired

- Nothing on super responders (tinnitus completely resolved as in Phase 1).

Overall I'm a little bit optimistic but I feel the paper is lacking crucial information.

 

[Jonno02]

One thing that jumps out to me is that the company they developed the device with, in2being, seem to be be experts in medical device manufacturing and also the regulatory process.

Seems promising!

 

[Nick47]

Eh, not the nicest feeling. However, I wonder if the remaining 35% could have benefited had they done more weeks of treatment? I don't see how it's impossible to think that their brains were adapting a bit slower.

@@dam, what do you expect? If we all had a migraine and you gave us all the same treatment, do you think 100% of us would get migraine relief?

 

[Brian Newman]

Some findings:

- People with more somatic tinnitus modulation movements benefited better, but it's stated that non-somatic tinnitus should also benefit.

- 7 people had worsened tinnitus during treatment (related/non-related), too little detail provided on adverse events. Subjects were removed from the study if their tinnitus loudness and TFI increased significantly for two consecutive weeks.

- Baseline was 5-10 years of tinnitus.

- Baseline TFI was around 40-45.

- Baseline loudness around 55 dB. Wow? This does not correlate to TFI and seems massive, I would be surprised if this was correct.

- Reduction of approximately 10 dB in tinnitus loudness.

- Non-responders not defined. Huge miss.

- Nothing on hyperacusis.

- Nothing on people who worsened (characteristics).

- Nothing on type of tinnitus (multi tonal etc) and how tinnitus was acquired

- Nothing on super responders (tinnitus completely resolved as in Phase 1).

Overall I'm a little bit optimistic but I feel the paper is lacking crucial information.

I'm glad they tested people who had had tinnitus for 5-10 years. I've never seen a good trial that has allowed new sufferers in, which definitely causes issues with the placebo. Most people I would say tend to panic for a while when they realize they could never hear silence again.

I have mad respect for Susan Shore, she's the real deal, a really smart researcher.

 

[AfroSnowman]

Eh, not the nicest feeling. However, I wonder if the remaining 35% could have benefited had they done more weeks of treatment? I don't see how it's impossible to think that their brains were adapting a bit slower.

Some of those 35% might have had a sub-significant response but still experienced some improvement. Not going back through the paper right now but if a significant response was X and some folks were X-1 or X-2, a portion of that 35% might be a differentiation without a difference.

 

[Nick47]

Nothing on super responders (tinnitus completely resolved as in Phase 1).

@InNeedOfHelp, this is something I looked for. It would be helpful to see individual data for each participant in an appendix. 5 super responders can drastically improve the mean response in 99 patients. It is encouraging that 65% had significant improvement though.

Also encouraging that:

Baseline was 5-10 years of tinnitus.

But again, if you had 5 participants who had had tinnitus for 20-30 years, this would dramatically increase the mean. Here I would like to see observations included in the discussion. Did they see differences correlated with duration? What were they?

Baseline loudness around 55 dB. Wow? This does not correlate to TFI and seems massive, I would be surprised if this was correct.

Possibly these participants did not have co-morbid OCD/depression and anxiety like many of us. It's also possible they did not have hyperacusis or unstable tinnitus so habituation was easier.

Nothing on type of tinnitus (multi tonal etc) and how tinnitus was acquired

My impression here is, from reactions from researchers, the type of tone and number of tones is of no interest to them. Unless it's typewriter tinnitus of course. To them it's a consequence of the pathology and doesn't change the physiology or treatment.

I would like discussion on unilateral versus bilateral tinnitus, however I don't think Dr. Shore sees this as important as she states "tinnitus is in the brain."

You provided a good summary and important questions though. I really wanted to see individual data!

 

[Kleiner]

Have you even read her papers? In any case, there's a pretty obvious reason why she only included people with somatic tinnitus in her studies. To the extent of our knowledge, the device will help these people the most.

Read her papers, and the papers she quotes in her papers. After doing so, like I have, you can formulate an adequate opinion on this topic.

First, you didn't understand what I meant, I'm simply saying that there is a huge interest in knowing how far her device can act in the auditory system. You would have to read her research to understand that.

And I remember the big announcement you made about Xenon Pharmaceuticals. Just wind down, don't be so aggressive.

Anyway, I wish you the best.

I'll take the time to read it in detail, but I'm not surprised with the results. Now, the challenge is to be able to adapt these results to a larger population, and perhaps to explore the ability of this device to act on non-somatic tinnitus and other forms.

Calibration will again be, in my opinion, the biggest challenge.

That being said, this is the first clinical trial that is not a total fiasco. Just for that, we can be happy for today.

 

[eagerUser]

Some findings:

- People with more somatic tinnitus modulation movements benefited better, but it's stated that non-somatic tinnitus should also benefit.

- 7 people had worsened tinnitus during treatment (related/non-related), too little detail provided on adverse events. Subjects were removed from the study if their tinnitus loudness and TFI increased significantly for two consecutive weeks.

- Baseline was 5-10 years of tinnitus.

- Baseline TFI was around 40-45.

- Baseline loudness around 55 dB. Wow? This does not correlate to TFI and seems massive, I would be surprised if this was correct.

- Reduction of approximately 10 dB in tinnitus loudness.

- Non-responders not defined. Huge miss.

- Nothing on hyperacusis.

- Nothing on people who worsened (characteristics).

- Nothing on type of tinnitus (multi tonal etc) and how tinnitus was acquired

- Nothing on super responders (tinnitus completely resolved as in Phase 1).

Overall I'm a little bit optimistic but I feel the paper is lacking crucial information.

Nothing mentioned on hyperacusis doesn't mean the device doesn't improve it. It may work or may not work on hyperacusis but there is a good chance it does. We'll see once the device is out!

 

[dipp]

- Reduction of approximately 10 dB in tinnitus loudness.

It's nice, but I don't think it's a life changer for people with severe tinnitus. Don't get me wrong, I would pay all I have and more, I would do anything in order to get a 5 or 10 dB reduction, but I don't think that would massively benefit a severe tinnitus sufferer. On the other hand, someone with mild tinnitus would be amazed to get their tinnitus halved or something like that.

 

[Christiaan]

It's nice, but I don't think it's a life changer for people with severe tinnitus. Don't get me wrong, I would pay all I have and more, I would do anything in order to get a 5 or 10 dB reduction, but I don't think that would massively benefit a severe tinnitus sufferer. On the other hand, someone with mild tinnitus would be amazed to get their tinnitus halved or something like that.

Maybe @linearb can chip in? If I'm not mistaken, his tinnitus was in the moderate-severe range but it was significantly reduced in intensity when he tested the Auricle device in the first trial.

 

[Nick47]

It's nice, but I don't think it's a life changer

A 6 dB reduction is a 50% reduction in volume. How is that not life changing?

 

[Kleiner]

- People with more somatic tinnitus modulation movements benefited better, but it's stated that non-somatic tinnitus should also benefit.

Can you tell me where you see that people with non-somatic tinnitus can also get a benefit, please?

 

[EDDTEKK]

This is the first time a study claims to reduce tinnitus loudness! That's amazing guys. Of course we have to see it in reality.

Even a 5 dB reduction would change my life enormously!

 

[AvidReader]

Some findings:

- People with more somatic tinnitus modulation movements benefited better, but it's stated that non-somatic tinnitus should also benefit.

- 7 people had worsened tinnitus during treatment (related/non-related), too little detail provided on adverse events. Subjects were removed from the study if their tinnitus loudness and TFI increased significantly for two consecutive weeks.

- Baseline was 5-10 years of tinnitus.

- Baseline TFI was around 40-45.

- Baseline loudness around 55 dB. Wow? This does not correlate to TFI and seems massive, I would be surprised if this was correct.

- Reduction of approximately 10 dB in tinnitus loudness.

- Non-responders not defined. Huge miss.

- Nothing on hyperacusis.

- Nothing on people who worsened (characteristics).

- Nothing on type of tinnitus (multi tonal etc) and how tinnitus was acquired

- Nothing on super responders (tinnitus completely resolved as in Phase 1).

Overall I'm a little bit optimistic but I feel the paper is lacking crucial information.

This covers my questions about the study/paper. Overall it is positive but there's a lot of missing information that would be useful to know, especially about those who worsened or saw no benefit.

 

[AnthonyMcDonald]

Just wind down, don't be so aggressive

I'm sorry, but where do you see me being aggressive? I was pointing out that it's ridiculous to post things like "oh it won't work" without any arguments to back up your opinion? Lol.

How Dr. Shore's device acts on the auditory system is literally explained in her research. No more, no less.

 

[Ngo13]

@InNeedOfHelp, this is something I looked for. It would be helpful to see individual data for each participant in an appendix. 5 super responders can drastically improve the mean response in 99 patients. It is encouraging that 65% had significant improvement though.

In Supplement 3, it states you can request depersonalized individual participant data from Dr. Shore but you need to have an academic or clinical interest and that it's to be used for future research. I'm not sure if we have anyone on here who would qualify.

 

[Nick47]

In Supplement 3, it states you can request depersonalized individual participant data from Dr. Shore but you need to have an academic or clinical interest and that it's to be used for future research. I'm not sure if we have anyone on here who would qualify.

Possibly @Markku and @Hazel who have been involved in tinnitus research (publications). The data will not be personalised; it will just say subject 1, 2, 3 etc.

 

[Jonno02]

The Shore Lab may well have data on secondary conditions like hyperacusis (if this wasn't an exclusion condition) but they may not have enough data to report any meaningful conclusions. And anything in this publication can come under fire from the FDA as they're mid submission.

Even a "the device may be beneficial for hyperacusis sufferers" could be a delay in approval as the FDA may want to see substantial data for making such a claim.

Clinical study publications aren't exhaustive, you need to report succinctly what you did and what the outcome was. This has moved more from the 'research' to 'development' and the publication does convey that. These publications are not the place for a lot of "maybes" and "might help X/Y". That sort of stuff really will be a focus for field data studies as they can expand the claims of the device with real world data, not the limited data set they have now.

Yes, there is a few things that could have been explained better like did anybody worsen? By how much? Or was this just a 'we had a failsafe in case we saw Lenire-type results," but overall I think it's a pretty good publication.

And remember, what we need is the foundation for a treatment. A genuine application that lowers the tinnitus volume. Other researchers will then be able to expand on what the Shore Lab have developed here and revision 2 or 3 etc. will be ever better. Every single technology, drug, device etc. at launch can be improved down the line.

 

[Karen1979]

So if my tinnitus gets louder when I clench my teeth or extend out my jaw, does that mean it is somatic? I have noise-induced tinnitus in one ear. I seem to have difficulty getting an answer on what exactly IS somatic tinnitus.

There is a supplemental list where all accepted maneuvers are listed, with their accompanied nerve.

Inclusion criteria as stated:

"Must be able to modulate their tinnitus with a somatic maneuver 19 (Simmons et al., 2008)" so based off this only one is needed. I can cause a massive spike with a cheek blow, indicating cranial nerve 7. If you can clench your jaw that indicates cranial nerve 5.

I'm not the best at understanding all of the technical jargon in these journals. Can anyone ascertain if there actually were dropouts or people that tinnitus got worse for? It seems to touch on 26 people leaving the clinical trial after being enrolled, but at what point did they leave is unclear to me...

They also said they stopped treating people if it made their tinnitus worse for two weeks in a row but then it didn't state if it actually did make tinnitus worse for anyone. I'm a little confused.

There were 26 dropouts, 16 self dropouts and 10 by the team. Out of the 26, 6 were because of an increase in tinnitus. These are all listed, but not at what point they dropped out.

 

[UKBloke]

Read the study once last night. Have taken a day doing other stuff just to let the basics drift into conscious; after all it's not often our community crosses the line where such critical milestones are concerned.

At this point there's only one question I'd like to know the answer to and that is; of the 4 people that dropped out of the trial of their own volition and the 2 people that the study team let go due to tinnitus worsening, how severe was their symptoms?

The science on this seems solid and Susan Shore has delivered on her promise. I'm willing for the Auricle device to do nothing for me as long as I can gauge the risk profile where a potential negative effect might be concerned.

Big hug to you all you guys. About fucking time we had some good news.

 

[RunningMan]

Eh, not the nicest feeling. However, I wonder if the remaining 35% could have benefited had they done more weeks of treatment? I don't see how it's impossible to think that their brains were adapting a bit slower.

Looks like while it was 65% who saw meaningful reduction in the active treatment group, 25% did in the control group as well. So the active treatment group was only 45% points higher on the metric. So some of those in the 65% group would most likely have had a placebo effect as well and not benefited significantly from the active treatment itself vs. what they would have experienced in the control group. But even if we account for that, it could be 50% or better who truly benefit from active treatment.

I just did some sampling of tones at these different dB levels. It's noticeable, but it's not nearly as much of a reduction as I would have hoped and probably wouldn't be much of a difference maker for me at only 6 to 10 dB reduction. I can get a lot larger reduction on a very short term basis using tones to cause residual inhibition. Of course yes, that's very short term.

 

[ErikaS]

- I appreciate those in this community who have a good eye to not only read studies such as this but analyze the information and then summarize it. Thank you for doing that as it helps with further understanding.

- With the baseline time of tinnitus being 5-10 years, I personally find the results to be a "wow". To be able to have a statistically significant change in suffers of 5-10 years in a matter of 6 weeks, not only speaks to the power of neuroplasticity but also the power potential of her device and the why and how it can work.

- I feel like the majority of the participants had to have had stable, moderate to loud tinnitus. So not reactive and/or bothersome hyperacusis. One could draw this assumption based on the fact that none of these people are not bothered/distressed enough to be active in an online community like this, because we have yet to hear from anyone other than @linearb from the first trial, so you'd have to assume the majority of these participants most likely "learned to live with it" and were able to carry on with life, and therefore possibly do not deal with the debilitation level that many of us do. I also think with this it wouldn't be a surprise that many of our distress levels would be notably higher than many of theirs at baseline before treatment due to many of us suffering from reactivity, distortions, hyperacusis, etc.

- I appreciate them stating that it could benefit those with non-somatic tinnitus, and I'm even more ecstatic that findings allowed them to state that.

- Hoping for all of us that FDA approval comes this summer.

 

[prowlinacage]

Susan Ellen Shore, Ph.D. is about to become a very wealthy woman!

 

[Nick47]

My biggest humdinger is the final cohort size. Originally it was posted as 400. Due to COVID-19, this was understandably not practical.

However, at 99 we still have a moderate size group to reduce the chances of a fluke/anomaly type situation. Small cohorts can provide false and misleading results, just think of Otonomy and Frequency Therapeutics. This is why many treatments fail at Phase 2 and Phase 3 as the bigger the cohort, the less chance the result was just by chance.

Now if I am right (if I'm wrong tell me), the data was collected from 56 participants as 37 discontinued or were unable to complete. It talks about ITT and PP, with ITT defined as intention to treat and PP as per-protocol. 56 were included in the PP analysis.

@Karen1979, in terms of NHS approval and the difficulties with them requiring level A-C evidence, they are looking at one trial of 20 patients and another trial of 56 patients. They will conclude that, due to the small and moderate cohorts, a larger trial is required.

 

[Jonno02]

Susan Ellen Shore, Ph.D. is about to become a very wealthy woman!

And bloody rightly so!