MemberDo you (or anyone else) remember if there was such a discrepancy between treatment Group 1 and Group 2 in the Phase 1 study? Though that was a study with only 20 patients so it might be harder to find such trends and patterns in there?
New University of Michigan Tinnitus Discovery — Signal Timing
- Thread starter Hudson
- Start date
Here are the results from the first trial. Seems like Group 2 did quite well in loudness, but not quite as good in TFI (although roughly comparable). Also notice the swift return to baseline.
- Dec 3, 2022
- 253
- Tinnitus Since
- 2012. Worsened 2022.
- Cause of Tinnitus
- Primarily loud music. Secondary - ETD + TMJ
Gotta say, that graph + the Group 1 from the recent study makes the recent study Group 2 look like the outlier. There's more data to say this works effectively than the contrary.
AfroSnowman
Member
- Jul 23, 2019
- 1,074
- Tinnitus Since
- 04/2019
- Cause of Tinnitus
- Nonnatural energy source
So the bottom of the bars on the graphs (the flat t's) are the maximum outliers?
- Feb 11, 2019
- 801
- Tinnitus Since
- 01/2014
- Cause of Tinnitus
- Headcold/Flu
The University of Michigan had a press release about it. Last time I quit a job, no one wrote a press release.
And, she is still affiliated with the University of Michigan. While obtaining emeritus status doesn't mean she left on good terms, not obtaining this status would certainly mean she left on bad terms and was being pushed out. It seems to me that she left on a high-note. Retiring right as a big publication comes out is very much retiring on your own terms.
Finally, I don't think the results are major headlines because most people wouldn't care about this. It is terribly meaningful for us, but the vast majority of the population wouldn't care in the slightest. The top headline for the NYTimes today was the war in Ukraine; WSJ's top headline is the SEC suing Binance; Bloomberg's is Apple's new headset; Fox's is a human interest story about mom/kid dying in plane crash; WaPo's is the war in Ukraine; USA Today's war in Ukraine; Business Insider's is Apple headset; and so on. While Dr. Shore's device is important to me, Apple is much more important to investors/consumers and the war in Ukraine is much more important as well.
I don't think the retirement is a bad thing. It is jarring that the Shore Lab is shutting down, but the fact that she is transitioning to a role in the private world and retained a connection to the university is reassuring.
Is this a marginalized, relatively trivial matter that most people with tinnitus don't care about?
1) Over 750,000 American Vets are so impaired by this that our Veterans Administration pays out over $2 billion annually for disability (and it is the #1 Medical Condition that afflicts Service members; Dr. Shore herself described the pervasiveness of this in a Senate Subcommittee Hearing);
2) Given that 11 million Americans have jobs that subject them to truly dangerous levels of noise, there must be a significant percentage that will eventually have this to a debilitating degree;
3) My Audiology Group said that they now get at least one tinnitus patient for every day of the year they are open; my ENT Doctor said that his colleagues have encountered these same numbers, and have surmised that it is quickly becoming an epidemic condition for the Retiring Baby Boom Generation.
- Dec 3, 2022
- 253
- Tinnitus Since
- 2012. Worsened 2022.
- Cause of Tinnitus
- Primarily loud music. Secondary - ETD + TMJ
I am. 3 very good groups and 1 not so great still points towards an effective treatment. I hope we get a bit more of a look at the data to find out what's gone on with Group 2.
What I do know is the 43 who didn't complete all the follow-ups are called the intent to treat (ITT) and therefore they will have some missing data points. I'm not sure what value is given to those missed appointments.
Like @UKBloke said, the washout period may not have been long enough, especially if the "sound only" has a small, but non-clinically significant effect.
Then there is the issue of super responders and those that got worse. Did the first treatment group have a handful of super responders and the 2nd group (placebo first) have a handful of non-responders or worsening? This will obviously have a large effect on the "mean" values. It is also why the bigger the cohort, the better, as a few super responders or non-responders will not affect the mean scores much. Randomisation is done to try and reduce this effect but it cannot always negate it completely.
Again, only individual subject data will tell us the answer.
Like @UKBloke said, the washout period may not have been long enough, especially if the "sound only" has a small, but non-clinically significant effect.
Then there is the issue of super responders and those that got worse. Did the first treatment group have a handful of super responders and the 2nd group (placebo first) have a handful of non-responders or worsening? This will obviously have a large effect on the "mean" values. It is also why the bigger the cohort, the better, as a few super responders or non-responders will not affect the mean scores much. Randomisation is done to try and reduce this effect but it cannot always negate it completely.
Again, only individual subject data will tell us the answer.
- Dec 3, 2022
- 253
- Tinnitus Since
- 2012. Worsened 2022.
- Cause of Tinnitus
- Primarily loud music. Secondary - ETD + TMJ
I'm sure I saw that missing values or non-compliant were stated as their baseline for worst case scenario. This is why I prefer PP over ITT.
NHPN-1010 from the Hough Ear Institute? That is dead in the water unless/until they find a new licensing partner to take that forward.
I'm not sure what form XEN1101 is going to be, whether it's a shot or a pill, but my money is on that being the first real cure for tinnitus. Though it will have to be used off-label as it will be an epilepsy drug.
I think Dr. Shore's device will be the first effective treatment to carry us through until the drugs that will save us will arrive. Heck, I hope the device will be so effective that we won't even care about a full cure for tinnitus. But we'll have to see!
BrysonKingMe
Member
- Mar 31, 2022
- 238
- Tinnitus Since
- 2016
- Cause of Tinnitus
- Paradoxical on Klonopin leading to a shitton of other proble
I saw that you took Trobalt with no success, why do you think XEN1101 will be more effective than Dr. Shore's device?
AnthonyMcDonald
Member
I got about an hour of relief per day for a couple of weeks taking Trobalt. But I habituated to it quickly. It went down from an hour to a 1/2 hour of relief per day, then to 20 minutes of relief per day and then 10 minutes, and then finally NO relief.
The drug produced a sickening high. The downside of the relief I'd felt is that it gave me a form of epilepsy. While I was coming down from the drug, I would have horrible full body convulsions, that felt like my entire body was being electrocuted. And those painful convulsions lasted for years, and now only manifest as weird out of control body movements as I fall asleep. I am no longer feeling the convulsions I'd felt while I was on the drug.
I do have some trepidation about XEN1101 because of my experience with Trobalt. I wouldn't call it no success, but maybe a heavily qualified one?
What I have hope for with XEN1101 is that it is an almost complete reformulation of Retigabine that is supposed to have done away with the horrible side effects of Retigabine (Trobalt). And it's supposed to be a much more powerful potassium channel activator than Retigabine. I will not be the first in line to try XEN1101, however I will pay close attention. And if the side effects have been eliminated and it does have a positive effect on tinnitus, then I will most definitely take it.
Part of the tinnitus equation is certainly the potassium channels in the brain. I believe that Dr. Shore is right in that the origin of tinnitus is the DCN. However, it's the function of the potassium channels in the brain to dampen hyperactivity in the brain, like the kind we experience in the DCN. And I know that potassium channels are one of the parts of the brain malfunction (becoming underactive) from noise exposure.
I think that if a drug can come along that will restore the function of the potassium channels in the brain, it could potentially be a very powerful solution for tinnitus sufferers.
Dr. Shore tested the device first on animals, didn't she? So does that mean that tinnitus is initially generated in the brain and that Dr. Shore's device might also help acute tinnitus?
Any ideas or comments?
Any ideas or comments?
AnthonyMcDonald
Member
For those wondering how loud the audio input is, you can find the details on the study article under the "Supplemental Content" tab → "Supplement 1 PDF". (Link to study).
It is 40 dB above the hearing threshold but no more than 90 dB.
It is 40 dB above the hearing threshold but no more than 90 dB.
StoneInFocus
Member
- Feb 21, 2022
- 500
- Tinnitus Since
- 2012
- Cause of Tinnitus
- Hearing damage, ear infections
One thing I am wondering is whether the immediate effects of Retigabine on tinnitus people reported were due to its potassium channel or its GABAA modulating properties. Especially since it seems that you developed some sort of tolerance to this relief effect. As far as I know, tolerance to the effects of potassium channel openers in regards to treating epilepsy has not been reported yet.
I am sorry about your experiences with Retigabine, sounds absolutely horrible.
I am currently taking the anticonvulsant Epidiolex, which was shown to open potassium channels Kv7.2/7.3 in mice, like XEN1101, instead of all five of them as was the case with Retigabine, and I haven't really noticed much effect on my tinnitus or pain hyperacusis so far, but no serious side effects either. I am currently on 35 mg/kg/day and titrating up to the maximum dosage of 50 mg/kg/day. Both Epidiolex and XEN1101 are not supposed to interact with GABAA receptors. People in the Retigabine thread have reported that they noticed a lasting improvement in their tinnitus after taking Retigabine for several months. A couple users also reported that their hyperacusis had disappeared completely. I am hoping I will notice more effects from the Epidiolex if I just take it for longer.
I have also taken Flupirtine, which opened potassium channels Kv7.2/3 and acted on GABAA receptors as well. It provided some temporary relief to my tinnitus after taking it, but on the comedown the tinnitus became even worse, although other people in the Flupirtine thread did not have those experiences and reported only positive effects. I had to quit Flupirtine after just a couple of days, I am still stuck with pills worth hundreds of dollars.
I'm not referring to any specific pill, hence why I specified 'a' pill. It could be a pill that hasn't been developed yet.
- Dec 3, 2022
- 253
- Tinnitus Since
- 2012. Worsened 2022.
- Cause of Tinnitus
- Primarily loud music. Secondary - ETD + TMJ
The motto of Frequency Therapeutics, or is it CBT researchers?
Now that we've had the time to digest Dr. Shore's original results and then the panic over Group 2, how are we all feeling?
T Toledo OH
Member
- Mar 12, 2020
- 173
- Tinnitus Since
- 2/26/20
- Cause of Tinnitus
- Likely loud noise and earbuds
These results do not look good. Very little real change unless I am reading it incorrectly.
- Dec 3, 2022
- 253
- Tinnitus Since
- 2012. Worsened 2022.
- Cause of Tinnitus
- Primarily loud music. Secondary - ETD + TMJ
You must be reading it incorrectly. The difference between the active and placebo groups are quite notable.
AnthonyMcDonald
Member
I see no reason for speculation. We just have to keep our hopes somewhat up and try it out en masse. Then we'll see who it works for, and who it won't work for.
Guitarplaya
Member
- May 24, 2021
- 2
- Tinnitus Since
- 2015
- Cause of Tinnitus
- Maybe hearing loss or maybe a cold that plugged my ears
I believe you may be reading it wrong. I'm seeing improvements ranging from -8 dB to -10 dB in tinnitus loudness, which is pretty damn good. There is a return to baseline it seems but I would not mind using the device every day for 30 minutes if it means having less bothersome tinnitus.
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