New University of Michigan Tinnitus Discovery — Signal Timing

[Mathew Gould]

It would be nice if Dr. Shore could answer questions or sum up her three-decade experiment every so often. One thing for sure is that by the year 3000, tinnitus will no longer be an issue.

 

[Jim Vasilakis]

Placebo doesn't reduce tinnitus volume by 10 dB, especially since most people's tinnitus loudness is below 20 dB. That kind of decrease is more than just a psychological effect. Also, a placebo doesn't last for months; it can last for some days, but it returns to baseline. That's why placebo is basically regression to mean.

 

[Joeseph Stope]

It would be nice if Dr. Shore could answer questions or sum up her three-decade experiment every so often. One thing for sure is that by the year 3000, tinnitus will no longer be an issue.

The year 3,000! Why, that's only 976 years away. Patience, boy, patience!

 

[dd314]

Placebo doesn't reduce tinnitus volume by 10 dB, especially since most people's tinnitus loudness is below 20 dB. That kind of decrease is more than just a psychological effect. Also, a placebo doesn't last for months; it can last for some days, but it returns to baseline. That's why placebo is basically regression to mean.

People with mild tinnitus talk about a placebo, but people with soul-shattering tinnitus know that a placebo doesn't touch it.

 

[RunningMan]

Placebo doesn't reduce tinnitus volume by 10 dB, especially since most people's tinnitus loudness is below 20 dB. That kind of decrease is more than just a psychological effect. Also, a placebo doesn't last for months; it can last for some days, but it returns to baseline. That's why placebo is basically regression to mean.

You're repeating the same thing, except you changed from 11 dB to 10 dB in this comment. It's still not something anyone was stating. My earlier response to that holds, along with a screenshot from the study for reference:

https://www.tinnitustalk.com/posts/708519

Also, the placebo effect lasted and continued to build over weeks. Placebo effects can be very strong and lasting.

That is quite amazing. I just brought it up in other posts when talking about what percentage of people could benefit. They always subtract the placebo percentage, but I think this can be kept as people have benefited.

Yes, for some people, if it lasts. An extra 5 or 6 dB reduction in loudness could be perceived as half as loud on top of any reduction from the active bimodal treatment benefit (when accounting for placebo).

 

[beefling]

The year 3,000! Why, that's only 976 years away. Patience, boy, patience!

Only 974 years? No problem. Just ask the mice.

 

[RunningMan]

People with mild tinnitus talk about a placebo, but people with soul-shattering tinnitus know that a placebo doesn't touch it.

Most people with mild tinnitus, like I was years ago, will never care enough to talk about it. Still, based on the study results, the bimodal treatment could be at least twice as effective as the control/placebo auditory-only treatment.

 

[Bob3382]

It would be nice if Dr. Shore could answer questions or sum up her three-decade experiment every so often. One thing for sure is that by the year 3000, tinnitus will no longer be an issue.

I hope something comes out soon. I recently developed tinnitus. Dr. Shore's device looks most promising.

 

[RunningMan]

I hope something comes out soon. I recently developed tinnitus. Dr. Shore's device looks most promising.

Yeah, you have to put "soon" into perspective here and be extremely patient.

After it gets approved in the U.S., getting all the parts to wide-scale distribution throughout the country will still take a long time. If you're willing to travel further, maybe you can get in on it earlier, which could be next year. It could take another year or longer before it's available closer to home for most people. Some people think it could be a few years. I'm trying to be optimistic that it will be sooner than that in my area. And then it's still a matter of whether you are among those it will help to any significant degree.

 

[Bhaveen]

I've just been reading about the first clinical trial as I had time to find the results today. Please excuse my ignorance, as I'm not great at reading charts. This comment by someone sums it up as:

Tinnitus reduction reached an average of 12.2 dB in the fourth week of active treatment. Of the 20 participants tested, 2 reported complete elimination of their tinnitus toward the end of the active treatment period.

These results seem better than the second clinical trial, and this first clinical trial was only four weeks long. Any thoughts, anyone? I would have thought a second trial would be more fine-tuned.

 

[Nick47]

Any thoughts, anyone? I would have thought a second trial would be more fine-tuned.

Yes, clinical trials with smaller cohorts can often produce less accurate results. As you mentioned, there seemed to be two super responders. Thus, in a group as small as twenty, this greatly pushed the average decibel reduction. Two to three super responders in a cohort of 100 participants would not affect the average much. That's why I was disappointed when the second clinical trial was reduced from an intended cohort of 400 participants to 100 participants.

 

[Jim Vasilakis]

I've just been reading about the first clinical trial as I had time to find the results today. Please excuse my ignorance, as I'm not great at reading charts. This comment by someone sums it up as:

These results seem better than the second clinical trial, and this first clinical trial was only four weeks long. Any thoughts, anyone? I would have thought a second trial would be more fine-tuned.

It was more fine-tuned since the results remained after the six-week period, whereas in the first clinical trial, tinnitus returned to baseline after four weeks.

The results of the second clinical trial were permanent.

 

[Muggumbo]

It was more fine-tuned since the results remained after the six-week period, whereas in the first clinical trial, tinnitus returned to baseline after four weeks.

The results of the second clinical trial were permanent.

Were they permanent or just much longer lasting?

 

[RunningMan]

I agree. More participants would have been better, along with a complete washout that resulted in a return to baseline like we saw in the first trial. Only 30 participants were included in the final PP analysis for receiving the active treatment.

Some of the fine-tuning actually broke the study, so they threw everything out after the crossover.

The active treatment in the second half of the studies—the second trial (left) vs. the first trial (right)—is circled below.

 

[slc]

I should be able to look this up myself, but I'm having trouble locating the link to the first study.

So, did the first study also use the same approach of sham treatment and then switch over to the actual treatment? Did they use a different number of weeks (compared to weeks used in the second study) for the washout after sham treatment before getting the actual treatment?

In the second study, those who received the sham treatment first did not respond as expected to the actual treatment; basically, there was no improvement, which I'm hoping might lead to further breakthroughs as to the reason and mechanism for the lack of improvement.

If someone has a link to the first study, that would be cool. I'm happy to go back and read it again. Thanks!

 

[Jim Vasilakis]

Were they permanent or just much longer lasting?

We don't know if the participants in the second trial returned to baseline, but they kept improving without using the device, which didn't happen in the first trial.

All in all, the common pattern is that the device improvement is NOT a placebo. In both studies, there were reductions in the 10-12 dB range. That is NOT a placebo. That's basically your tinnitus going from moderate to mild.

 

[Nick47]

I should be able to look this up myself, but I'm having trouble locating the link to the first study.

So, did the first study also use the same approach of sham treatment and then switch over to the actual treatment? Did they use a different number of weeks (compared to weeks used in the second study) for the washout after sham treatment before getting the actual treatment?

In the second study, those who received the sham treatment first did not respond as expected to the actual treatment; basically, there was no improvement, which I'm hoping might lead to further breakthroughs as to the reason and mechanism for the lack of improvement.

If someone has a link to the first study, that would be cool. I'm happy to go back and read it again. Thanks!

They used otherwise the same trial design, except instead of four weeks, they used six weeks.

 

[RunningMan]

I should be able to look this up myself, but I'm having trouble locating the link to the first study.

So, did the first study also use the same approach of sham treatment and then switch over to the actual treatment? Did they use a different number of weeks (compared to weeks used in the second study) for the washout after sham treatment before getting the actual treatment?

In the second study, those who received the sham treatment first did not respond as expected to the actual treatment; basically, there was no improvement, which I'm hoping might lead to further breakthroughs as to the reason and mechanism for the lack of improvement.

If someone has a link to the first study, that would be cool. I'm happy to go back and read it again. Thanks!

The first trial also used the crossover study method, but it was four weeks of treatment and four weeks of washout vs. six weeks of treatment and six weeks of washout of the second trial. You can also see that in the timeline in my previous post's screenshots.

 

[slc]

The first trial also used the crossover study method, but it was four weeks of treatment and four weeks of washout vs. six weeks of treatment and six weeks of washout of the second trial. You can also see that in the timeline in my previous post's screenshots.

Thanks, @RunningMan.

Yes, I surmised this was the case from your chart, but I wasn't totally certain. Thanks for clarifying this.

I had previously theorized that somehow the sham sounds or the sham nerve stimulation had stopped the crossover group (receiving first sham and then actual treatment) from experiencing reduced tinnitus, but obviously, there is a time component as well—as you all have clearly explained.

I know I'm reworking the territory discussed, but which of the three variables or combinations thereof prevented improvement (and, as I mused earlier, could this help inform future research)? And perhaps there are other variables I missed.

1. Sham sounds
2. Sham nerve stimulation
3. Number of washout weeks (four was OK, but six blocked results)

 

[GregCA]

Yes, clinical trials with smaller cohorts can often produce less accurate results. As you mentioned, there seemed to be two super responders. Thus, in a group as small as twenty, this greatly pushed the average decibel reduction.

Isn't it common practice to use the median rather than the average, specifically to avoid problems caused by outliers?

 

[Anomalous]

I find it really odd how in the first trial, the loudness was reduced by 12 dB in only four weeks but didn't have a carry-over effect, while in the second trial, the loudness was reduced by only 6 dB in six weeks and did have a carry-over effect.

 

[ploughna]

Regarding the points above describing various inconsistencies in results, I have to hope that during all this time we're left waiting, there's some work going on to refine and fine-tune the treatment parameters for optimal results. It'd be pretty disappointing if the only thing happening is fundraising and preparing an FDA submission.

 

[slc]

I find it really odd how in the first trial, the loudness was reduced by 12 dB in only four weeks but didn't have a carry-over effect, while in the second trial, the loudness was reduced by only 6 dB in six weeks and did have a carry-over effect.

I'd have to reread the studies, but didn't they fine-tune the treatment for the second study? If so, this might account for the carry-over effect.

 

[Anomalous]

I'd have to reread the studies, but didn't they fine-tune the treatment for the second study? If so, this might account for the carry-over effect.

The previous study, which observed cumulative reductions in tinnitus over the 4-week treatment phases, suggested that increasing treatment duration would enhance treatment efficacy; thus, the current study design and bisensory treatment parameters were the same as those of the previous study except that the treatment phases were extended to 6 weeks.

 

[Nick47]

I have to hope that during all this time we're left waiting, there's some work going on to refine and fine-tune the treatment parameters for optimal results

They can't do this without running another trial.

 

[RunningMan]

Thanks, @RunningMan.

Yes, I surmised this was the case from your chart, but I wasn't totally certain. Thanks for clarifying this.

I had previously theorized that somehow the sham sounds or the sham nerve stimulation had stopped the crossover group (receiving first sham and then actual treatment) from experiencing reduced tinnitus, but obviously, there is a time component as well—as you all have clearly explained.

I know I'm reworking the territory discussed, but which of the three variables or combinations thereof prevented improvement (and, as I mused earlier, could this help inform future research)? And perhaps there are other variables I missed.

1. Sham sounds
2. Sham nerve stimulation
3. Number of washout weeks (four was OK, but six blocked results)

I'm not sure if there really was any sham nerve stimulation. I know there was that entry in some of the documentation that @gameover posted about using a different timing for electrical stimulus, but everything else for the second trial reads that the sham was only auditory.

Included participants were randomized to either treatment group 1, which received active (bisensory) treatment, or group 2, which received the control (auditory-only) treatment.

Even the first trial said the sham treatment was auditory.

All subjects and investigators were blinded as to whether subjects received an active (bimodal) or sham (unimodal-auditory) treatment for the duration of the study.

 

[Pixelito]

The most interesting part of the study is the placebo group, which consisted of test subjects who experienced a perceived reduction in tinnitus volume simply because they believed they would.

That should say something about the power of the mind. Temporary or not.

 

[F-u-T]

The most interesting part of the study is the placebo group, which consisted of test subjects who experienced a perceived reduction in tinnitus volume simply because they believed they would.

That should say something about the power of the mind. Temporary or not.

Maybe listening to sound stimulation at the same frequency as their tinnitus reduced their tinnitus level. When they added electrical pulses, it had an even greater effect.

 

[RunningMan]

Maybe listening to sound stimulation at the same frequency as their tinnitus reduced their tinnitus level. When they added electrical pulses, it had an even greater effect.

They added the electrical stimulation after the auditory-only in the second half of the study as circled in red below, and it did not have a greater effect.

I asked ChatGPT this question:

If a medical study shows that a treatment provided clinically significant improvement for 65% of the study participants, but the placebo control arm of the study showed clinically significant improvement for 25% of the study participants, what is the true efficacy of the treatment?

To determine the true efficacy of the treatment, you would typically compare the improvement rates between the treatment group and the placebo group. In this case:

• Treatment group improvement rate: 65%
• Placebo group improvement rate: 25%

So, the treatment's efficacy can be calculated by subtracting the placebo group improvement rate from the treatment group improvement rate:

65% - 25% = 40%

Thus, the true efficacy of the treatment, accounting for the placebo effect, would be 40%.

 

[Jonno02]

Maybe listening to sound stimulation at the same frequency as their tinnitus reduced their tinnitus level. When they added electrical pulses, it had an even greater effect.

I did this when my tinnitus first worsened. I got a new tone at 4.4 kHz, left it alone for nearly year to see if it would go away; it didn't. I started listening to the same tone with my phone under my pillow as I slept. For a month the 4.4 kHz tone kept reducing until it became masked by my usual 6 and 12 kHz tones. I don't notice it anymore at all.

The same thing didn't work for my other tones, though, unfortunately. I am very reactive to residual inhibition. I can play any frequency, and my tinnitus will disappear completely for half a minute.