New University of Michigan Tinnitus Discovery — Signal Timing

Let's not get too far ahead of ourselves. I just hope I would be among the possibly 50% (maybe less) of people who receive a clinically significant reduction in tinnitus volume using the device and that it's meaningful for me personally. Anything more will be a bonus.

 

It's an interesting question. You would think so with continued damage to the inner ear. Once the device is on the market, we can be sure the limits are going to get pushed and tested in every way. Sure as hell not by me.

I don't think we ever got an answer about what happened with that one test subject who suffered a setback with loud noise exposure during testing. But the test period was so limited, we also have no idea what the results will be from long-term usage of the device.

 

65% had a clinically significant reduction and the rest had a reduction as well.

 

It's also possible the other 35% could have had a significant reduction as well if they could have used the device longer. It will be nice when we no longer need to speculate.

 

It's clear to me that the device will help the majority of patients with somatic tinnitus which again is the majority of tinnitus patients overall.

I'm not throwing headlines like 90% of tinnitus patients will have 70% reduction but it seems to me the majority will have SOME reduction.

 

Combining Dr. Shore's device with XEN1101 should potentiate its effects.

Though, I'm not up to par with Dr. Shore's device a hundred percent. Does it help with hyperacusis at all, does anyone know?

 

We need to factor in 20% in the placebo arm had a clinically significant reduction.

I'm opting for a 20-30% achieve noticeable reduction and 20% small reduction. 50% diddly squat.

 

It was actually 53% of the full group of 99 participants, and that's before discounting that 20% of the placebo/control group had clinically significant reduction. So, that's a 33% points difference better than placebo. That doesn't look nearly like 65%. Subtract for the placebo effect, and you're going to see a lower number for effectiveness who were truly helped by the device.

Weed out those who got worse and dropped out or didn't follow the protocol, and the results look a little better for those who remained, so the PP group had 65% having clinically significant improvement with the active treatment vs. 25% control (placebo). So, that's 40% points better with the active treatment.

Real world results, which I expect will include some people who couldn't have qualified for the study, will probably have lower results than the ITT group (all 99 participants). But, hopefully we will see close to 50% or more with a perceived improvement when combined with the placebo effect. I'm willing to give it a shot.

Exactly!

 

I think that if you don’t experience any relief within 6 months, it’s nonsense to proceed with the device. It’s the same with Lenire. This is also valid for Neurofeedback. The doctors have always told me about this 6 month period. It seems to be some standard neurological treatment limit.

 

It doesn't sound too promising. This is all that was mentioned in the Q&A:

 

Yes, we need to be happy a treatment is coming to market but we also need to temper expectations, I think. It will be interesting to see how TU Delft goes as it may be a more expedient way to access treatment for the 97% of us who live outside America.

TU Delft is also a bit of a heavyweight in terms of technology.

 

A few of us are aiming to attend a tinnitus symposium that will be hosted by TU Delft in February.

Wouter Serdijn and Dirk de Ridder, who are working on a device similar to Auricle, are included as speakers.

More information can be found in the thread created by Christiaan.

 

With all the kindness and respect I can express in this message, there is no reason for any sort of negative speculation on Tinnitus Talk. Please keep it to yourself.

You have no idea what the treatment outcome will be if 1.) used longer than a half hour per day 2.) used longer than 6 weeks 3.) electrical stimulation at greater levels.

You just don’t know. So please, people here are fragile. If you’ve got something positive to say, great. If you’ve got something factual to say, thank you. Otherwise there is no purpose in the negativity...

 

I agree with the positivity but also I think it's a good idea for us to keep pragmatic in our approach to the Michigan device. I think it's a lot safer mentally for everyone to be cautious and to follow the data to make a call on whether it will work or not. A blanket approach of predicting it works for everyone will see some people here devastated when the device is launched and if unfortunately, it doesn’t work.

I'm sure some will post very positive experiences and some will post some maybe more disappointed versions - personally I want to set the bar low for myself on expectations of the device when I finally (hopefully) get to utilise it.

However, I still feel that if this doesn’t work for you, & it works for others, it's a major positive for us all as it will show tinnitus can be treated. The research focus into other devices and medications will be incredible. The real-world data after 1 year of millions of people using this will be a serious step in the right direction, and, hopefully, a lot more of a unified research approach will take place.

Even one person here saying it’s worked for them is a victory for us all in the long grass.

 

It's going to take more than one person saying it worked to feel like a victory. We've had that with Lenire.

In the Shore study, 25% of the PP control group and 20% of the ITT group had clinically significant improvement based on their THI scores when they had not even received the bimodal stimulation treatment. So, even a small victory feels like it needs to be a higher percentage of positive feedback than that, just based on the facts of the study, especially early on in use when the placebo effect could be strong at work.

I personally like to avoid speculation of what benefit or negative response there will be to using it longer than a half hour per day, using for longer than 6 weeks, or changing electrical stimulation levels. I like to stick to the facts of the study (the first half before the crossover) and what it showed using the study protocol rather thinking we can know or do better ourselves.

The real world data will certainly be interesting to see, and I'm optimistic it will be better than Lenire.

 

So let me ask you guys a different question.

We know the basic principle of how this device works, but there are cases where it did nothing at all, right?

Do we know why it doesn't work? Is the "all the signals must go through the DCN" theory flawed? If it isn't flawed, then why is the success rate so low, even for somatic tinnitus?

Maybe the participants lied, meaning they did not have somatic tinnitus, or something else? Maybe the settings were not adjusted properly?

 

Is 65% that low? Seems high to me.

Maybe user error? We know that at least one was careless enough to attend a concert. Test subjects are not always reliable.

 

As I mentioned a few posts back, the results of 65% (PP) and 53% (ITT) for clinically significant reduction were only 40% and 33% points better than a placebo / control group for the PP group and ITT group (all 99 participants) respectively, despite the selective criteria of the study, and that's ignoring the second half of the study. So, keep your expectations in check while maintaining optimism.

As with any treatment, results are mixed with different people. Hopefully future treatments will be more successful. At least it's a start we can learn from while benefiting possibly up to half of sufferers.

 

Not gonna happen. After waiting x amount of years and spending $5k or whatever this device is going to run, there will be zero chance of keeping expectations in check. I'm sure most here feel the same.

If the thing doesn't work for me, fine. No regrets... I'm sure there will be some return policy or secondary market to recoup any losses.

 

Yes, I have been wondering about this as well. They are both bimodal approaches; however,

Perhaps this has already been looked out, but if the study followed the participants for a longer time, one would expect most of the placebo group to eventually revert back to baseline, BUT the treatment group might retain the improvement. Just a thought.

 

Right, as long as treatment continued. That's why I mentioned a couple posts back that the early feedback may be more positive due to the placebo effect being stronger then, so I would like to see a higher percentage of success to feel the device is really working beyond a placebo effect. And, if someone maintains that improvement over time, it's more convincing the device really helped. I think this happened early on with Lenire where people thought it was helping and later came to the conclusion it wasn't - possibly just an early placebo effect.

 

Agreed. All guessing aside though, and with the risk of sounding judgemental towards Dr. Shore - it’s just somehow baffling to me that one can spend 20 years of their life researching something and have the pivotal results be ”meh”. Like... how? Why?

 

A more positive yet still logically consistent take on this kind of placebo-arithmetic might be to consider that in an actual therapeutic setting, no one will know whether any effect is from placebo or not. One might speculate that the placebo effect will be more transient in some way, but there really isn't any evidence of that one way or another.

So I think it's reasonable to view the data from the study simply as: 65% of the people felt clinically significant relief after using the device. Since any causal effect is unknowable in a therapeutic setting, having a mindset of "there is a 65% chance I will feel relief after using the device" is not, to my thinking, irrationally optimistic.

 

I'd argue that can be blamed on how little we understand the human brain. This approach is in line with the idea that tinnitus is caused by the brain being hyperactive. There's a few examples of treatments having positive results with this understanding. Deep Brain Stimulation, the Kv7 modulators, and Neromodulation like the Auricle device all follow those lines of logic. The brain is a confusing and fragile organ that has to be approached with caution. Which 20 years of research is both cautious and thorough. It doesn't make it a silver bullet, but it adds to the pile of research that will be used to find a cure one day.

 

Not sure if anyone else has found this before? But the code for the TinnTester application used in these studies has been posted online for quite some time on GitHub[1]. It's a bit of a mess to be honest, clearly a research tool, and you can't run it since it relies on a "TDT PA5"[2] device to handle generating the tones at a precise volume and frequency. But it's all there. There are also some docs & a video walkthrough of the app under the "Media" folder.

[1] https://github.com/auricle-inc/TinnTester-auricle
[2] https://www.tdt.com/component/pa5-programmable-attenuator/

 

Great find! I guess the PDF slides are interesting to see how the software GUI works.

 

Why do you think it’s a bit of a mess? The setup steps in the slides looks quite thorough and it’s obviously designed to be run with specific hardware to generate calibrated tones.

I actually think it looks quite decent.

 

65% is aiming high. The 65% includes only the PP group receiving active treatment before the crossover, which is only 30 participants, after excluding those getting worse tinnitus or receiving no benefit and not figured in the analysis. Add back in those 5 excluded participants, you're closer to 54% of 35 analyzed who received clinical meaningful improvement when receiving the active treatment. But as mentioned, 25% could be placebo effect as that is what the control side of the study showed. Also keep in mind that some people were not allowed to participate in the study as they were expected to have less positive outcomes, so those figures for tinnitus improvement would have likely been lower with more patients from the broader public who want to use the equipment who couldn't have qualified for the study, like some members here.

One thing I mentioned up thread was:

So, without the placebo effect, it's bound to be about 20%-25% less who truly benefit rather than 54%, but hopefully not too low so that we can chalk it up to the device actually working effectively for a substantial percentage of people rather than just the placebo effect benefit, which isn't likely to last long term for many. Personally, the placebo effect hasn't helped me with quite a few different things I've tried, so I want to see real lasting reduction in tinnitus for 50% of users, which may be too optimistic. 50% including those with the placebo effect is a lower bar to reach.

Some of those early users will come to realize it's not truly working and was just a placebo effect just as with many other things that have been discussed on Tinnitus Talk in regard to supplements, Lenire, etc.

 

I'm not going to dig back through the study, I'm kind of at the whatever will be will be with the state of Auricle, but I wonder what you think about the noise reduction numbers?

I think that when THI type numbers are used as a measure of treatment success, it leads us into the world of placebo effects, which have clinically meaningful differences that mean nothing in the real world.

I'm more interested in % of folks reporting lower volume of tinnitus as measured/reported apparently objectively by the use of TinnTester. What percentage of active participants in the first 6 weeks of study showed lowered volume?

 

The placebo/control effect on volume reduction was shown in the results just as it showed a reduction in the TFI scores from baseline for placebo/control, so placebo shows up in both metrics.

The study used TFI scores for population percentages. The volume reductions were ranges and averages. But in the study, they had some graphs and included this comment: