Retigabine (Trobalt, Potiga) — Petition to the ATA

[OnceUponaTime]

@attheedgeofscience Thank you for the file. I appreciate your help.

 

[dan]

you'd think more would be done about Tinnitus.

yeah you'd think....but we can't even sign a petition for a Retigabine study.

 

[RaZaH]

I have no problems signing a petition , I just do not think its time yet . Realize that only one person has had full recovery, I would at least want to see one more person achieving that . Having said that , just the effects that it seems to have on T warrants further study and even a petition but I still think we should gather more data , that cannot hurt and in fact will make such a petition much more likely to achieve something.

 

[attheedgeofscience]

Hereby an informal update on the ATA petition (I indicated in an earlier post I would provide some kind of input of my own involvement in this).

I have now contacted four researchers at the professor-level for their input on the known- or suspected- pharmacological mechanism-of-action of Trobalt. Two have responded; two are pending - where one of them probably will not respond, I think. GSK has also been contacted, but will require another attempt. The feedback from the two professors has been somewhat limited, but essentially they cannot provide an exact MoA for Trobalt (because it is simply not known - at least not to the high standards of academia that professors work by; that's my take on it).

The professors are "nameless", but below are their responses:

Dear Mr. Hansen:
Thank you for your recent e-mail. Although the in vitro research was done in my lab, Dr. <name withheld> is the expert on tinnitus. I have already suggested that we should quantify the neurotoxicity of this compound before we address specific mechanisms. However, we do not have the resources to start new projects. Support for research has been cut substantially.

Dear Jakob, Thank you for your interest in the work. We do not know the mechanism of how retigabine (Trobalt) decreases induced firing of neurons, or whether this activity could suppress symptoms of tinnitus. In light of the known side effects of the drug (blue eyes, skin, tremor, etc) it is not likely to be useful for treating tinnitus, especially long term. Dr. <name withheld>'s lab is currently working on potentially more effective alternatives with fewer or no side effects. However, securing funding for this research remains an uphill battle.

I hope to get a bit more insight on the MoA from the last remaining professor who will hopefully respond.

If we do not get an expert testimony on the MoA, then we can potentially proceed by referring to a recent research paper on Kv modulators.

As with any project, a number of questions present themselves - such as:

1. Will the ATA accept signatures from non-US citizens?
2. Does it make a difference if we collect 100, 500, or 1000 signatures, and if so...
3. which IT platform would be best for handling the petition?

There is also inclusion criteria to consider for the informal trial. Additionally, we are pending input from other resources who have not responded yet - which delays the whole process.

I do not represent the group; I am just a member. Who "we" are does not matter, but there are some people working on the project behind the scenes. And so far we have been pretty busy - more than 100 PMs have been exchanged at this point. I do not plan to make any commitments towards this project - perhaps something will materialize, perhaps not. You never know.

I also do not intend to answer any questions because there isn't really any reason to (at this stage).

 

[dan]

I have no problems signing a petition , I just do not think its time yet . Realize that only one person has had full recovery, I would at least want to see one more person achieving that . Having said that , just the effects that it seems to have on T warrants further study and even a petition but I still think we should gather more data , that cannot hurt and in fact will make such a petition much more likely to achieve something.

I fully agree with you in your points. But if and when the time comes, we need to move on this full steam ahead.
We would need to petition the ATA directly, because only it could allocate funds for this mini study, as you can see researchers are running on empty.

 

[RaZaH]

Agreed.

 

[amandine]

Why are we directing this only to the ATA??
No response yet as to the fact that this is not an american problem only.....
Do you really think that the ATA will do something and or fund anything for this? Maybe....
Can we not petItion the Global Fund to include Tinnutus as part of its remit? Probably not but at least we can start to think in these terms.
Why dont we get the idea out that this is an emergency medical problem that is growing in numbers globally day by day much as HIV grew.
Go on and have a good laugh at this post but I think we all think too small on this. Are we so unimportant? Millions around the world suffer from this ailment yet these numbers are so unimportant?
Even if the global fund is not the place surely the ATA is just too damned small.....it may be a good start and somewhere to go on this but I feel that there should be more pushing in larger far more important organisations than the ATA...
If you approach the global fund with the idea that there may be something here that is ''clearly ??'' helping to reduce or eliminate T, they may be interested or be able to push another organisation or get more political will behind finding a cure or providing funding for it.
Maybe another pig just flew past my window - I dont know - but straight to the top is certainly not only the ATA.

A campaign (petition) was launched recently thru Change.org and within 2 days it had 10K signatures which is now at 241K signatures and a whole lot has been achieved for spreading awareness and getting help for the problem and assistance with the problem. It has attracted huge media attention too.
And the petition was for: Children with learning difficulties.
Just one petition put on line at change.org by one person and look at what he achieved so quickly! So one person can do this for children with learning difficulties (and he directed the petition only at the UK govt) why cant we achieve same or more with a petition for T funding / research / re labelling of trobalt...?

 

[attheedgeofscience]

Can we not petItion the Global Fund to include Tinnutus as part of its remit? Probably not but at least we can start to think in these terms.

This (potential) petition is about engaging the ATA in a study that would move Trobalt from being off- to on-label in the treatment of tinnitus.

If just one of the tinnitus associations could succeed with a study, then the outcome of that would apply everywhere. So there is no need to engage the BTA or the AuTA, for example. Additionally, the ATA is probably the only one of the tinnitus associations that would have the needed resources to undertake the project.

Why dont we get the idea out that this is an emergency medical problem that is growing in numbers globally day by day much as HIV grew.

Advocacy is a topic that I have covered a fair bit, already:

https://www.tinnitustalk.com/threads/bta-refuses-to-fund-drug-and-stem-cell-research.6599/

However, the reality of advocacy is that when 100% of a group's population complain about something, a maximum of 1% is likely to actually get involved.

So there is a lot of "we" out there, but not a lot of "I"...

 

[valeri]

I agree that we should address other relevant bodies, not about this particular topic (retigabine) but more awareness to the problem is definetly needed.

 

[valeri]

Just bumping this up!
Wondering if there are any updates.

 

[attheedgeofscience]

Wondering if there are any updates.

I can only speak for myself (and not the group as a whole).

I don't have any further updates at this point; I am still pending a reply from a specific professor in the US. If I do not have a reply by Tuesday (one full week), then I will probably need to go to "plan B". Personally, I do not see a reason as to why there needs to be a MoA for a petition. I would be more comfortable referring to a recent research paper on potassium modulators as a means of demonstrating the theoretical potential of Trobalt as a treatment against tinnitus.

I know another member of the group is pending a response from the ATA.

Number crunching on this board's "trial" participants should be completed, I believe.

Then there is the collection of signatures themselves. A platform needs to be selected for that and then the petition needs to run for a certain period of time to collect the signatures required.

So one way or another, I do not see this petition (and its final deliverable) as happening in "one month". Even if the petition is accepted and the SAB gives it the thumbs up, then it will take time to do the study itself (ie. you will need participants and put them through the treatment which could in itself be eg. 3 months). Don't ask me for specifics, but it would be at least 6 months from now before such a study could be finalized - at least! As I see it, anyway.

 

[valeri]

@attheedgeofscience
6 months is still better than never
Thank you for doing all this Jacob!
I personally don't think we need to waste time waiting for some professors reply.
Even though I understand the credentials it could have, there is still plenty of evidence how retigabine may improve tinnitus.
Also the results from our members here are not to be dismissed or ignored.
Hopefully we can get somewhere with this.

 

[valeri]

@attheedgeofscience

Sorry to bother you but I forgot to ask, at the beginning of this threat it was mentioned that military should be informed or contacted, has this been done or this is not considered at the moment?

 

[preslys]

I can only speak for myself (and not the group as a whole).

I don't have any further updates at this point; I am still pending a reply from a specific professor in the US. If I do not have a reply by Tuesday (one full week), then I will probably need to go to "plan B". Personally, I do not see a reason as to why there needs to be a MoA for a petition. I would be more comfortable referring to a recent research paper on potassium modulators as a means of demonstrating the theoretical potential of Trobalt as a treatment against tinnitus.

I know another member of the group is pending a response from the ATA.

Number crunching on this board's "trial" participants should be completed, I believe.

Then there is the collection of signatures themselves. A platform needs to be selected for that and then the petition needs to run for a certain period of time to collect the signatures required.

So one way or another, I do not see this petition (and its final deliverable) as happening in "one month". Even if the petition is accepted and the SAB gives it the thumbs up, then it will take time to do the study itself (ie. you will need participants and put them through the treatment which could in itself be eg. 3 months). Don't ask me for specifics, but it would be at least 6 months from now before such a study could be finalized - at least! As I see it, anyway.

at least 6 months we will have the autofony reply about the résults of their clinicals trials
since autofony has the same mechanism function as trobalt

 

[attheedgeofscience]

at least 6 months we will have the autofony reply about the résults of their clinicals trials
since autofony has the same mechanism function as trobalt

The petition some members of this board are in the process of preparing, would in the ideal situation end up becoming a study with the aim of demonstrating Trobalt's efficacy in the treatment of tinnitus, and hence potentially move Trobalt from being off- to on-label in the treatment of tinnitus.

Whatever happens with Autifony's clinical trial would have no impact on that. The only purpose of a study such as the above would be to "widen" the availabililty/applicability of Trobalt for other purposes - ie. tinnitus.

From my point-of-view, at least.

 

[attheedgeofscience]

@attheedgeofscience

Sorry to bother you but I forgot to ask, at the beginning of this threat it was mentioned that military should be informed or contacted, has this been done or this is not considered at the moment?

We are not planning to threaten anyone...

I do not see the armed forces as the being the vehicle of the study. I could see how the armed forces could be a stakeholder and a sponsor of clinical trials and/or a lobbyist of funds for tinnitus research.

I have no intention of contacting the US centre of excellence for hearing loss, myself; I am not a US citizen; I am not a member of the US armed forces. There are members on this board who are.

I'd prefer not to answer anymore questions. This petition may not even lift off the ground, and so until there is a more concrete case to present in public, I do not see a good justification for posting in this thread.

If someone wants to try Trobalt out, they can - as stated earlier - already today visit their doctor's office and get a prescription (although it may, admittedly, be a harder with off-label drugs).

 

[kaycee]

If by"relief" you mean never hearing severe tinnitus (that I heard every second of the day for 5 months when not in the shower- and occasionally even over the shower)- then count me in

My tinnitus reduced significantly within a couple weeks of starting retigabine - to the point of being very tolerable - I would have been thrilled if the improvement would have stopped there-- but it didn't-- I basically can't hear my tinnitus even when searching for it now, occasionally I'll hear it when plugging my ears (but not always when plugging ears)

I have no doubt that retigabine is responsible for my initial volume reduction.butto tell you the truth the continued improvement that I have seen in the past couple months-- I'm not sure if its from retigabine (because I am off of it now) or through brain plasticity being able to file away the insignificant sound that I was left with

How is one prescribed this?

 

[valeri]

We are not planning to threaten anyone...

Spelling mistake!
Of course we don't won't to do that!

 

[preslys]

The petition some members of this board are in the process of preparing, would in the ideal situation end up becoming a study with the aim of demonstrating Trobalt's efficacy in the treatment of tinnitus, and hence potentially move Trobalt from being off- to on-label in the treatment of tinnitus.

Whatever happens with Autifony's clinical trial would have no impact on that. The only purpose of a study such as the above would be to "widen" the availabililty/applicability of Trobalt for other purposes - ie. tinnitus.

From my point-of-view, at least.

you're right we know never if autofony will show good results .we have to achieve our goal to have new version of trobalt without the side effects.

 

[beemovie]

I don't think the manufacturer will do a study for tinnitus. I am not sure if they have even resolved the eye issues with the drug yet as stated in the FDA warning on the drug: http://www.fda.gov/Drugs/DrugSafety/ucm349538.htm

 

[attheedgeofscience]

you're right we know never if autofony will show good results .we have to achieve our goal to have new version of trobalt without the side effects.

Our goal - our petition - if it goes forward would not have the aim of developing a new and modified version of Trobalt. The goal would simply be to prove - or disprove - Trobalt's efficacy in the treatment of tinnitus.

 

[attheedgeofscience]

As this board knows, I have been in touch with various top-level professors regarding tinnitus research - professors who are at-the-edge-of-science within their field of work. A third researcher has come back with a reply regarding the pharmacological mechanism of action of Trobalt. The reply regarding Trobalt is identical to that of the other two professors: the mechanism of action in relation to tinnitus suppression is not known. However, the researcher did share with me an interesting development...

Dear Jakob,
Thank you for your interest in my research. There is one tinnitus update that I would like to share with you: we have developed and tested a novel and more specific Kv7.2/3 (KCNQ2/3) activator that works much better than retigabine both for epilepsy and for tinnitus. This novel Kv7.2/3 activator is more specific than retigabine and is less toxic, but keep in mind that all this work has been performed only in mice and rats. The manuscript describing this work in detail will be submitted for publication within the next month or so and I hope that the new compound will hopefully go to clinical trials soon.
I am not an MD and therefore clinical trials, effects of drugs on tinnitus sufferers, medical advice, and clinical applications of my findings in humans are outside of my expertise/control. I know the exact MOA of retigabine on Kv7 channels (you can read it in my 20xx publication in <name withheld>), but I do not know the MOA of retigabine on tinnitus and therefore I can not answer your question.

[Note: To protect the source, I had to edit one sentence which now reads in part: "20xx publication in <name withheld>" in the quote above]

So at this point it is probably safe to say that the mechanism of action is not known (ie. three different researchers have now independently confirmed that). However, it is probably also safe to say that the improvements the +10 trialees on this forum have experienced in terms of tinnitus suppression is not imagined. There really is good reason to suspect that Trobalt works for some cases of tinnitus with a specific cause. A paper titled "Pharmacodynamics of potassium channel openers in cultured neuronal networks", released online March 25th, 2014, helps support this "fact" (theoretically).

As I stated in an earlier post, I do not represent the petition group; I am just a member (who shares information in public).

I do not know what the next step will be. There has been several pieces of information to take in from various sources over the past week - and many, many discussions back-and-forth in our offline PM-system. Perhaps the petition will go ahead, perhaps not. My own position is that a study to move Trobalt from off- to on-label in the treatment of tinnitus should take place "somehow". It would represent a "quick-win" way of addressing a need of treating tinnitus pharmacologically while other compounds are tested and clinical trials being executed. It would also help establish potential treatment protocols such as treatment duration and dosage regimes - and potentially determine if Trobalt could be curative in some cases (ie. not require continuous suppressive treatment). To my knowledge, no one on this board has so far reached a daily dose of 1200mg. What would the effect be if such a dose is maintained for eg. "a week"? The paper above mentions how dosage is potentially quite important if the desired pharmacological effect is to be achieved. There are many (remaining) questions to be answered in my opinion...

 

[valeri]

It's good to know that there's another potential solution to this nightmare!

 

[dan]

It would represent a "quick-win" way of addressing a need of treating tinnitus pharmacologically while other compounds are tested and clinical trials being executed. It would also help establish potential treatment protocols such as treatment duration and dosage regimes - and potentially determine if Trobalt could be curative in some cases (ie. not require continuous suppressive treatment).

Beautifully said - and I hope this answers people's question as to why this is a good idea.
I really hope my idea(petition for a Trobalt tinnitus study) becomes a reality.

 

[Markku]

After correspondence with the ATA, the organization has informed me that instead of gathering signatures for a petition, it would suggest a written proposal justifying the benefits from undertaking a clinical study of Trobalt.

The background for this decision is that the ATA does usually not engage in research by itself, but prefers instead to gather research proposals from leading scientists within the field of tinnitus research.

This change would likely lighten the burden we have in front of us (as we no longer require a certain number of signatures). 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.

We intend to set up a new offline workgroup with members from the TT-community. The aim will be to write a proposal and include relevant findings from our informal study along with observations from recent scientific literature. The funding "requirement" from the ATA will also need to be discussed as the outcome of any study would ideally not just benefit the TinnitusTalk community, but essentially any patient suffering from severe tinnitus, anywhere in the world.

 

[tomm]

As this board knows, I have been in touch with various top-level professors regarding tinnitus research - professors who at-the-edge-of-science within their field of work. A third researcher has come back with a reply regarding the pharmacological mechanism of action of Trobalt. The reply regarding Trobalt is identical to that of the other two professors: the mechanism of action in relation to tinnitus suppression is not known. However, the researcher did share with me an interesting development...


[Note: To protect the source, I had to edit one sentence which now reads in part: "20xx publication in <name withheld>" in the quote above]

So at this point it is probably safe to say that the mechanism of action is not known (ie. three different researchers have now independently confirmed that). However, it is probably also safe to say that the improvements the +10 trialees on this forum have experienced in terms of tinnitus suppression is not imagined. There really is good reason to suspect that Trobalt works for some cases of tinnitus with a specific cause. A paper titled "Pharmacodynamics of potassium channel openers in cultured neuronal networks", released online March 25th, 2014, helps support this "fact" (theoretically).

As I stated in an earlier post, I do not represent the petition group; I am just a member (who shares information in public).

I do not know what the next step will be. There has been several pieces of information to take in from various sources over the past week - and many, many discussions back-and-forth in our offline PM-system. Perhaps the petition will go ahead, perhaps not. My own position is that a study to move Trobalt from off- to on-label in the treatment of tinnitus should take place "somehow". It would represent a "quick-win" way of addressing a need of treating tinnitus pharmacologically while other compounds are tested and clinical trials being executed. It would also help establish potential treatment protocols such as treatment duration and dosage regimes - and potentially determine if Trobalt could be curative in some cases (ie. not require continuous suppressive treatment). To my knowledge, no one on this board has so far reached a daily dose of 1200mg. What would the effect be if such a dose is maintained for eg. "a week"? The paper above mentions how dosage is potentially quite important if the desired pharmacological effect is to be achieved. There are many (remaining) questions to be answered in my opinion...

Incredible work ATEOS. Thank You.

If Trobalt went on-label, Valeant Pharmaceuticals and GlaxoSmithKline might take notice due to all of the veterans and other suffers being given it to try and see their bottom line increase. Since that drug would be the only game in town and ripe for competition, that's going to get he rest of the industry's attention as well. It's hard not to feel optimistic about what that might lead to in the future.

 

[Rog]

@Markku you're a fine man

 

[attheedgeofscience]

For all those interested in potassium modulator research as well the original idea to present a petition to the ATA, this post contains important information.

I have received feedback from yet another top-level scientist within the tinnitus research field. The response can be seen below and is self-explanatory (ie. it does not require knowledge of my original e-mail to the professor in order to be understood with clarity). I have had to edit the response in a few places, however (I do not disclose the names of sources in public, but the original e-mail content is known by certain members of TT).

There is now enough information gathered in order to proceed with a modified petition to the ATA (as indicated by Markku's post earlier on in this thread). We have now obtained a speculated MoA and there is additional supporting evidence from recent literature that Trobalt has the therapeutic potential to suppress and/or cure tinnitus in some cases. We also have anecdotal evidence from an informal trial done with volunteers from TinnitusTalk.

At this stage, there is therefore no reason why a letter of request for a study of Trobalt should not be written and presented to the ATA. I would kindly ask people who believe they have the sufficient skills to partake in such an exercise. There are several doctors on this board and I would encourage them or anyone with sufficient medical knowledge to step forward and help prepare a letter of request for a study of Trobalt. I would also encourage the number crunching of the data from the informal trial to be completed and presented with clear quantitative improvements of volunteers (on a scale from 0-10) and with a clear summary of inclusion/exclusion criteria exercised (eg. min. dosage level, treatment duration period, etc.)

The letter below also mentions the need for further funding in order to pursue additional research. I would welcome anyone who believes they have the skills - either directly or indirectly - to become part of workgroup tasked with fundraising when/if the need arises.

As stated in earlier posts, I do not represent the petition group; I am just a member who shares information in public. My views do also not necessarily represent those of the TinnitusTalk staff.

attheedgeofscience
06/DEC/2014.

Dear Mr. Hansen:

I am in receipt of your comments about Trobalt (Retigabine), as a prelude to a clinical trial for treating tinnitus, to be underwritten by ATA that you are seeking. I appreciate your interest in our work. I am aware also that you have been in contact with <information withheld by ATEOS: statement refers to name(s) of research colleague(s)>. I have been in contact also with the other <information withheld by ATEOS: statement refers to name(s) of research colleague(s)>. Thus, they have asked me to respond in their behalf as pertains to your requests. We would surmise or speculate that the MOA of Trobalt as follows:

"The primary mechanism of action of Trobalt (Retigabine) is Kv channel activation, which hyperpolarizes the membrane and reduces action potential firing. Another possible mechanism is GABA receptor activation, which increases the magnitude of the membrane potential and reduces the triggering of action potentials".

As per us contributing further to the petition, and the comments you included herein:

1) Your expert testimony that doing a study on Trobalt in relation to tinnitus suppression would be worthwhile under certain circumstances such as - example only - treatment duration not exceeding 3 months and in cases of patients with "catastrophic tinnitus".

2) Your expert testimony on the theoretical possibility of Trobalt having a curative potential (as opposed to only a treatment potential requiring continuous medication for suppressive effect).

3) Anything else which could potentially be of value (contacts with <information withheld by ATEOS>).

We feel strongly that we are not in a position nor do we have sufficient experimental data to comment on these three (1, 2, 3) statements.

If there is to be funding of research as pertains to this topic for further data collection as per our research platforms, then we would greatly appreciate consideration of receiving such funding. We are presently operating our labs without sufficient internal or external funding. Quantitative data on Trobalt neurotoxicity is lacking and can be established by our laboratories. A systematic search for and evaluation of compounds with similar effects to Trobalt, but with less toxicity, is perhaps also possible from our labs.

 

[Codaz]

All fine with me @attheedgeofscience but when are doctors ever going to listen?
Most dr's are there to do their job, do the "standard" things like pull a tooth, prescribe an MRI, stitch a wound. You need specialized people first, and then those that are willing to test it out. To invest unpaid hours, with an uncertain outcome. Then a lot of volunteers (they need payment as well) for this heavy medicine. In the Tinnitus Textbook from 2010 is that the potential market for tinnitus is close to a billion dollars. But no one picks it up of the bigger pharmaceutics. And they are the ones that are in control, not the ATA.

It's not like you gather a bunch of dr's, order 15 boxes of trobalt and go. Bureaucracy demands that it's insured, set up well, applies to international standards etc. If you start tomorrow you end up in 2016 before it starts.

 

[Zimichael]

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