Retigabine (Trobalt, Potiga) — Petition to the ATA

[Mark McDill]

Can some of the US ex-military people TT members maybe step in here and do some outreach snooping in the VA behemoth to see if there could be some 'bright spark' person involved in their hearing/tinnitus treatment division that could perhaps be of help here? Seems like a potential "cure" is scraping along without sufficient funding whilst "acceptance" techniques and "dulling meds" are swallowing billions of $$$ re vets. (And I mean cure! - as in these 'modified' Kv drugs specifically for tinnitus, not Trobalt per se, though it's all we really have to work with at present).
Lots of starter leads in prior postings c/o ATEOS like: http://hearing.health.mil/

Best, Zimichael

Zimichael
I'll look into it; I retired in 2005 but I've heard they have done a lot since then.

Mark

 

[UserID]

Can some of the US ex-military people TT members maybe step in here and do some outreach snooping in the VA behemoth to see if there could be some 'bright spark' person involved in their hearing/tinnitus treatment division that could perhaps be of help here? Seems like a potential "cure" is scraping along without sufficient funding whilst "acceptance" techniques and "dulling meds" are swallowing billions of $$$ re vets. (And I mean cure! - as in these 'modified' Kv drugs specifically for tinnitus, not Trobalt per se, though it's all we really have to work with at present).
Lots of starter leads in prior postings c/o ATEOS like: http://hearing.health.mil/

Best, Zimichael

I believe the VA hospital that is most involved with tinnitus research is in Portland, OR. The head man's name escapes me right now. He may still be in the system, maybe not. So many employees from years ago are retiring these days. My care comes from the James A. Haley Veterans hospital in Tampa, and I cannot say enough about their willingness to serve the veteran.

To aid in sound therapy, they provided for me an iCom transmitter that sends my mp3 mitigation recordings into my hearing aids, and another transmitter for my TV. That is what I have had most success with, sound therapy, as opposed to so many other avenues I've tried since 1972. I developed T, as you may have noticed, from artillery, and the use of loud pneumatic tools while in the Navy.

I will ask my audiologist if she has heard of Trobalt.
David

 

[attheedgeofscience]

Can some of the US ex-military people TT members maybe step in here and do some outreach snooping in the VA behemoth to see if there could be some 'bright spark' person involved in their hearing/tinnitus treatment division that could perhaps be of help here?

I think this is an excellent point @Zimichael. For sure there are resources if the right avenues are found.

My idea - which I have voiced with the anonymous petition group of TinnitusTalk - is that a workgroup be set up with the task of meeting certain goals. One of these goals would be fundraising. To facilitate this process, I initiated the first steps by setting up the idea of a talent pool.

My hope is that there is enough will amongst at least certain members on TT to get things moving. There are many bright people on TT (just look at the talent pool thread!) - and it does not take a Ph.d in management administration to set up a workgroup of say 5-7 people tasked with exploring funding through avenues such as:

1) The VA armed forces services/The US military's hearing centre of excellence
2) Health authorities
3) Public funding (crowdfunding)
4) Grants in relation to eg. websites with a charity purpose
5) Funding from "celebrities with tinnitus" eg. musicians/entertainers/actors

I have helped with the ATA petition process by reaching out to top level scientists with the aim of getting sufficient evidence of Trobalt having some therapeutic effect in terms of tinnitus suppression. The expert testimony from the group of scientists I have presented earlier today can/should become part of the ATA letter of request (this will add weight to the material presented to the ATA). As should the scientists' request for funding of further research.

Regarding the US military's hearing centre of excellence, I have previously supplied material on their focus areas to the TT- board, but I will do so again below.

 

[Zimichael]

Thanks Mark & David... I think it helps if one has been in the service here to get some credence. I would hope that someone buried in the VA or vet care woodwork may see the writing on the wall and go: "WOW! there are these drugs that look very, very promising for actually stopping Tinnitus but these research folks are saying they're begging for funding? And you TT lot have your own "dumb bomb" version and are getting definitive results, so that makes this a little less like 'just another good tinnitus cure idea' and potentially revolutionary...Let me make some calls and I'll get back to you!"

Here I am referring of course not just to a one track thing of a "Retigabine label change" but also the overall reason for that change, which is to get more juice behind the whole Kv channels approach and the clear evidence that there are "effects" even with a version not even made for Tinnitus!

best, Michael

 

[Dr. Nagler]

Excellent work by @attheedgeofscience. Very thorough and very helpful. Thank you.

@Markku and all, I am still quite willing to write up a draft of the petition, but I continue to wait for answers to two questions:

1) How many people on this board have taken Retigabine in the hopes that it will in some way improve their tinnitus? (To be clear, I am talking about those who have taken as few as a single pill.)

2) Of those, how many achieved what they would consider to be some degree of meaningful relief that they attributed at least in part to the Retigabine?​

These questions are crucial, for without an unambiguous statement regarding the anecdotal Retigibine experience on this board, no matter how well-worded a petition might be, it will have no teeth at all.

Please do not refer me to some sort of spreadsheet compilation of data. Just provide a numerical answer to each of the two above questions.

Dr. Stephen Nagler

 

[attheedgeofscience]

@Markku and all, I am still quite willing to write up a draft of the petition, but I continue to wait for answers to two questions:

1) How many people on this board have taken Retigabine in the hopes that it will in some way improve their tinnitus? (To be clear, I am talking about those who have taken as few as a single pill.)

2) Of those, how many achieved what they would consider to be some degree of meaningful relief that they attributed at least in part to the Retigabine?

These questions are crucial, for without an unambiguous statement regarding the anecdotal Retigibine experience on this board, no matter how well-worded a petition might be, it will have no teeth at all.

Dr. Nagler, it was our intention to formulate the results with a bit more quantification along the lines:

"All participants had been taking Trobalt for a minimum of 4 weeks and reaching a minimum daily dosage of 600mg before their final improvement score on a scale of 0-10 was reported."

The criteria, above, would exclude certain participants - objectively - either because they did not stay on Trobalt for long enough or because they did not reach a high enough daily dosage. The initial number crunching was already completed 2 weeks ago, but I believe the main contributor to the exercise complained that the progress reports of the participants were reported in a non-timely fashion - and hence do not allow for benchmarking improvements within the same treatment duration period (eg. some participants would report their improvements weekly; others bi-monthly, and so on...).

It was also our intention to include certain relevant footnotes such as any participants achieving lasting relief upon cessation of the treatment. The results of these participants would otherwise be lost in the mathematical averages - needless to say...

I think the off-line petition group needs to revisit this and settle on an appropriate way forward.

But our intention is to report the results not as a single number, but instead as a paragraph containing at least some indication of inclusion/exclusion criteria, dosage regime, treatment duration, as well as the number of participants.

It is also the intention to get all trialees to sign-off their progress reports (anchoring their validity; this is the Internet, after all...). If a specific participant is not willing to do so, then that forces a re-computation of the data, of course.

As for my own part, I am willing to sign-off the accuracy of the statements I have provided to the board regarding the statements I have collected from various research professors. As I see it, this verification can be achieved in two ways: either I testify that the data is true and accurate, or a second person - eg. Markku - confirms independently with the source that the information provided is correct.

Additionally, this board now has a lawyer willing to assist with issues of a non-time consuming nature (perhaps relevant to the above).

 

[tomm]

Can some of the US ex-military people TT members maybe step in here and do some outreach snooping in the VA behemoth to see if there could be some 'bright spark' person involved in their hearing/tinnitus treatment division that could perhaps be of help here? Seems like a potential "cure" is scraping along without sufficient funding whilst "acceptance" techniques and "dulling meds" are swallowing billions of $$$ re vets. (And I mean cure! - as in these 'modified' Kv drugs specifically for tinnitus, not Trobalt per se, though it's all we really have to work with at present).
Lots of starter leads in prior postings c/o ATEOS like: http://hearing.health.mil/

Best, Zimichael

Found a PDF which shows what the Navy is looking for. It's very through and spans everything from understanding, reducing, curing and preventing tinnitus. I'll paste it here. Mods I apologise - please remove to new thread if this is off topic for the petition.

It's thorough and concise. If we can play to one of the elements of the VA it might help. Especially if we reference/target their official requirements. We hit point 5 (treatment).

Hearing deficits have a deleterious impact on operational readiness and
service member quality of life. The field of hearing preservation and restoration covers a
broad area of research topics. Research in the following areas is required.

1. Capability to preserve and restore hearing.

a. Studies of hair cell regeneration. This may include stimulation of endogenous cells for replacement of lost cells or transplantation of stem and/or progenitor cells. Endogenous stimulation may include genetic, neurotrophic, pharmacologic, or other approaches. Stem cell research may include adult or embryonic stem cells. (Note: If the offeror anticipates that the use of embryonic stem cells may be needed to perform the proposed research, it must provide adequate information to demonstrate compliance [or a plan of compliance] with applicable executive orders, statutes, regulations, and other guidance on use of pluripotent stem cells. This is expected to include information about how the stem cells to be used in the proposed research were derived.)

b. Prevention and/or treatment of hair cell loss. This may include pharmacologic approaches, prevention of apoptosis, manipulation of signalling systems, enzyme and/or antioxidant treatment/mimicry, etc., and the development of novel cochlear implant technology.​

2. Capability to identify individual/population susceptibility to noise-induced hearing loss/tinnitus

a. Studies on genetics/biomarkers. This may include assessing the variations in DNA sequencing to elucidate genotype single nucleotide polymorphisms that are correlated to NIHL and/or tinnitus, studies on inheritable traits as risk factors, or other biomarker/biometric approaches.​

b. Development and validation of assessment tools. This may include studies on the use of otoacoustic emissions, pre-existing hearing loss, or other reliable methods/factors that can rapidly assess susceptibility.
​

3. Development of tools and methodologies that rapidly assess changes in hearing thresholds and recommend the most effective individual mitigation/treatment strategies.

4. Advanced training tools for the audiologist and service member that demonstrate hearing loss and tinnitus, and that promote the correct use of hearing protection.

5. Surgical and nonsurgical approaches to the treatment of combat-related middle and inner ear trauma, including reconstruction, replacement, or augmentation of hearing structures.

6. Basic research elucidating the etiology of tinnitus.

7. Development of prototype technologies or specifications for prototype development to monitor/reduce individual noise exposure, either through passive/electronic hearing devices or noise exposure reduction.

Link source.

 

[RaZaH]

Maybe the progress reports should be "quantized" to one per week or maybe two reports per week?
I have not been sure what interval to use for my reports and without a fixed interval I have tendency to report when I feel better, not sure if this applies to others.

Feel free to remove if not proper for this discussion

 

[valeri]

Can somebody please put all this in some sort of ABCD plan?

Now we are going back to VA, possibly military?, fund rising.....
The possible cure may be laying under our noses but as usual it's a lack of money for research!

What precisely are we focusing on?

Thank god for our in house lawyer!

 

[attheedgeofscience]

Can somebody please put all this in some sort of ABCD plan?

1) Finalize "petition" (= letter of request)

1. MoA: done.
2. Informal trial evaluation: "nearly" done.
3. No requirement for signatures; this is a "letter of request" for a study to be undertaken and does not require signatures.
4. Legal matters: sign-off on the accuracy of the data provided.

2) Fundraising...

1. To contribute - financially - towards the study with the aim of moving Trobalt from off- to on-label in the treatment of tinnitus.
2. To support future research for more advanced/specific potassium modulators with fewer side-effects and/or better treatment effect.

Now we are going back to VA, possibly military?, fund rising.....

True, but the TT-board did not choose its own circumstances:

However, it may be required that we - the proposal owners - have to contribute financially towards the proposal. The financial burden we would have to carry needs to be clarified with the ATA.

(In my next life, I should consider becoming a personal assistant, I think...)

 

[valeri]

@attheedgeofscience

In your next life you will be as brilliant as now, no matter what you choose to do

 

[Dr. Nagler]

Dr. Nagler, it was our intention to formulate the results with a bit more quantification along the lines:

"All participants had been taking Trobalt for a minimum of 4 weeks and reaching a minimum daily dosage of 600mg before their final improvement score on a scale of 0-10 was reported."

It is also the intention ...

Well my thought would be to provide a straightforward simply-worded direct brief attention-getting document that could be readily understood by all who would sign it as well as all who would read it, keeping in mind that 90+% of both groups would be non-scientists. Such a document would immediately capture the interest of its intended audience, the (lay) Board of Directors of the Anerican Tinnitus Assiciation, and would include an offer to provide more information and/or clarification if requested.

You seem to be interested in depositing a veritable tome in the laps of these folks, and I just do not think that's the way to go.

So I'll leave it with you at that and wish you success.

Dr. Stephen Nagler

 

[tomm]

Anyone who is on LinkedIn might want to check if they are closely connected with any of the organisations we're looking to approach - send an 'InMail' and get a 'stealth' intro to someone inside the company without having to be screened as if you were selling something.

Maybe there is a medical, management or legal specific equivalent website that may work even better.

 

[OnceUponaTime]

My hope is that there is enough will amongst at least certain members on TT to get things moving. There are many bright people on TT (just look at the talent pool thread!) - and it does not take a Ph.d in management administration to set up a workgroup of say 5-7 people tasked with exploring funding through avenues such as:

How much money do we need to raise?

 

[attheedgeofscience]

How much money do we need to raise?

Most important right now is if there will be a funding requirement for a Trobalt study. This is for the ATA to inform us about.

As for funding future research (which is also important provided it is directly relevant to treating tinnitus), I am pending feedback from the group of researchers. But this is a separate point to be tackled.

 

[attheedgeofscience]

Well my thought would be to provide a straightforward simply-worded direct brief attention-getting document that could be readily understood by all who would sign it as well as all who would read it, keeping in mind that 90+% of both groups would be non-scientists.

Noted, Dr. Nagler.

I have asked the "number cruncher" from the TT-petition group to deliver the figures you specifically request. If anything, the data you require makes it all much easier, I would say. I cannot see any reason why the data should not be available to you soon.

And thanks.

 

[Dr. Nagler]

Noted, Dr. Nagler.
I have asked the "number cruncher" from the TT-petition group to deliver the figures you specifically request. If anything, the data you require makes it all much easier, I would say. I cannot see any reason why the data should not be available to you soon.
And thanks.

Glad to help.

Dr. Stephen Nagler

 

[UserID]

There are those of us who are on other meds for various physical conditions. Always, the question that pops up in my mind is if another med or supplement will keep me from additional side effects to contend with. Sometimes I am fighting the effects more than I am the root intent. How tiring it all has become.
David

 

[xanaxvictim]

@attheedgeofscience
Please pm me I'm in contact with a Professor in charge of ENT clinical trials in a local university (he is also my T doctor), I am going to ask him for his opinion on the possibility of trialing Retigabine on T patients, whether off-label or a open label pilot study. I need information w.r.t. which university/research institution is currently conducting research on possible Retigabine derivatives/second generation molecules acting on Kv7.2/3 channels. I told him about AUT 00063 and he seems to be interested (he didn't know that before). I hope he is open minded enough to consider such a possibility but I need evidence/information that someone is working on Kv7 family Potassium channels. I know you want to withhold their names but please pm me I'm only going to mention it to my professor and not disclosing this to anyone else. I need your help. Thank you very much.

 

[attheedgeofscience]

For those interested, here is a basic summary of the data reported so far by participants of the informal study of Trobalt.

The summary is - or should be - fairly self-explanatory. I will not go into details in terms of analysis and assumptions; I am simply presenting an output (no more, no less).

One point to take note of is: for a participant to be included in the summary, it is necessary to have reported both a start user form AND at least one progress user form (otherwise basic calculations cannot be computed). There were also other assumptions, but the one just mentioned is the main one.

Lastly, the purpose of an informal study is to demonstrate some kind of basic efficacy; the purpose is not to demonstrate consistent efficacy across the spectrum of participants, correlation with dosage level, chronicity, etc. Since this is a small trial, specific interesting data points could be chosen on a simple conditional basis eg. for those participants who experienced an improvement of 4 points of intensity or more, what was the chronicity in those cases? This can then lead to further conclusions.

 

[xanaxvictim]

chronicity as a predictor of treatment outcome:
single variable linear regression, n=17, slope=-0.333 (95%CI [-2.4, 1.8]), SD=1, P-value=0.744, R2 = 0.007
based on available data, chronicity of onset is slightly negatively correlated with outcome but it is not statistically significant
interesting if we can include age, other medication use, cause, dosage, duration of RTG use etc. for a multi-variable regression analysis

ps. Ricardo reported a complete remission of T when he was on RTG but a c/t erased all ground he had gained, he took RTG 1 month after onset

 

[Philemon]

Thanks @attheedgeofscience for this very interesting summary

interesting if we can include age, other medication use, cause, dosage, duration of RTG use etc. for a multi-variable regression analysis

I don't think our sample is large enough to perform such kind of analysis ... but still interesting to notice than based on those data, chronicity doesn't seem to be a real factor of efficacy, thanks for this ... still it would need to be confirmed by a real and sounded clinical study ('cause doing statistical inference based on our non-random and small sample is a bit tricky)

 

[valeri]

If this study would go ahead what would be the time frame before getting any results or conclusions?

 

[Codaz]

The intensity looks a bit iffy to me. Since we don't have T volume measurements it's highly subjective that you have improvement. I talked to someone on this forum via PM . She says that she sometimes does not hear her T. Good for her, but the ENT does not believe her. That it's sometimes gone. So improvement is not recognized by dr's.
If only we had some kind of measuring method to measure how loud our T was... like helmet you put ono your head which measures T level and tone frequency... So everybody could hear what we do.

 

[SoulStation]

The intensity looks a bit iffy to me. Since we don't have T volume measurements it's highly subjective that you have improvement. I talked to someone on this forum via PM . She says that she sometimes does not hear her T. Good for her, but the ENT does not believe her. That it's sometimes gone. So improvement is not recognized by dr's.
If only we had some kind of measuring method to measure how loud our T was... like helmet you put ono your head which measures T level and tone frequency... So everybody could hear what we do.

I don't understand why we didn't talk about doing Audiograms (especially those with a main tinnitus signal =< 8 Khz)
And a high frequency audiogram for those with tinnitus above 8 khz. I mean if this drug truly attenuates the tinnitus signal perception then there should be less interference with out brains ability to distinguish the pure tone signal at that frequency. (In my case my main tinnitus is 3.9 khz and my audiogram from June shows a small 5-10 db dip at that frequency). So why wouldn't we be able to hear those frequencies better? I'm not speaking of true damage to the ear cells, but I know that they do go hand in hand.

 

[preslys]

For those interested, here is a basic summary of the data reported so far by participants of the informal study of Trobalt.

View attachment 4050

The summary is - or should be - fairly self-explanatory. I will not go into details in terms of analysis and assumptions; I am simply presenting an output (no more, no less).

One point to take note of is: for a participant to be included in the summary, it is necessary to have reported both a start user form AND at least one progress user form (otherwise basic calculations cannot be computed). There were also other assumptions, but the one just mentioned is the main one.

Lastly, the purpose of an informal study is to demonstrate some kind of basic efficacy; the purpose is not to demonstrate consistent efficacy across the spectrum of participants, correlation with dosage level, chronicity, etc. Since this is a small trial, specific interesting data points could be chosen on a simple conditional basis eg. for those participants who experienced an improvement of 4 points of intensity or more, what was the chronicity in those cases? This can then lead to further conclusions.

good work @attheedgeofscience if I will have a lab you will be the first i'll contact to work but you forgot to add two columns about dosage and side effects.

 

[attheedgeofscience]

good work @attheedgeofscience if I will have a lab you will be the first i'll contact to work but you forgot to add two columns about dosage and side effects.

The material presented yesterday was tailored for a specific purpose in relation to some of the work that we are doing behind the scenes. I then decided to share the table (in public) since I had already prepared it for other reasons.

Both dosage and side effects are text-fields in the data forms (allowing any number and character to be entered instead of predefined values such as 3x150, 2x200, 4x400, etc.). It would require data cleansing in order to use the data. However, as soon as data is manipulated - even if correctly done - it is no longer virgin data. In any event, dosage would only be relevant if we wanted to correlate it with other findings eg. "improvement" vs. "dosage". But we are not interested in that for this type of small and rather informal study. Side effects to be useful would need to be categorized and/or computed into a number by the participant to easily evaluate (eg. "serious effects" = 5, "no side-effects" = 0). Again, this was not done in advance when the data forms were initially prepared - because this would have required foresight of the situation - and so it is what it is...

 

[preslys]

The material presented yesterday was tailored for a specific purpose in relation to some of the work that we are doing behind the scenes. I then decided to share the table (in public) since I had already prepared it for other reasons.

Both dosage and side effects are text-fields in the data forms (allowing any number and character to be entered instead of predefined values such as 3x150, 2x200, 4x400, etc.). It would require data cleansing in order to use the data. However, as soon as data is manipulated - even if correctly done - it is no longer virgin data. In any event, dosage would only be relevant if we wanted to correlate it with other findings eg. "improvement" vs. "dosage". But we are not interested in that for this type of small and rather informal study. Side effects to be useful would need to be categorized and/or computed into a number by the participant to easily evaluate (eg. "serious effects" = 5, "no side-effects" = 0). Again, this was not done in advance when the data forms were initially prepared - because this would have required foresight of the situation - and so it is what it is...

you're right, now you can send your data to ATA. I hope il will be a scrutiny.

 

[Codaz]

I don't understand why we didn't talk about doing Audiograms (especially those with a main tinnitus signal =< 8 Khz)
And a high frequency audiogram for those with tinnitus above 8 khz.

Getting an Audiogram > 8 Khz is very difficult as ENT's don't believe in them. One said to me it's an unreliable test.
I only did one in Rotterdam and Ghent, both were "fine".

 

[Hudson]

The material presented yesterday was tailored for a specific purpose in relation to some of the work that we are doing behind the scenes. I then decided to share the table (in public) since I had already prepared it for other reasons.

Both dosage and side effects are text-fields in the data forms (allowing any number and character to be entered instead of predefined values such as 3x150, 2x200, 4x400, etc.). It would require data cleansing in order to use the data. However, as soon as data is manipulated - even if correctly done - it is no longer virgin data. In any event, dosage would only be relevant if we wanted to correlate it with other findings eg. "improvement" vs. "dosage". But we are not interested in that for this type of small and rather informal study. Side effects to be useful would need to be categorized and/or computed into a number by the participant to easily evaluate (eg. "serious effects" = 5, "no side-effects" = 0). Again, this was not done in advance when the data forms were initially prepared - because this would have required foresight of the situation - and so it is what it is...

You presented this to the ATA already?

Thanks