Retigabine (Trobalt, Potiga) — Petition to the ATA

[lapidus]

I would say that acoustic trauma is damage to the ear caused by noise, so it is a different category.

I got my tinnitus from syringing and I don't consider it acoustic trauma.

It wasn't loud enough to be considered as such.

I see. I always though the syringing was a noisy procedure since so many people have gotten T from it and therefor thought it was noise induced T. So what you are implying is that potassium modulators probably won't have any effect on us who got T from loud noise? Well that sucks

 

[OddV]

For those of you in the double super secret working group... how does the data look for those of us that got it from ear infections? DannyBoy is the only one I'm aware of that is on RTG that got it in that fashion.

Also, is there anything I can do to assist? East Coast of the US, so could take some action items that needed to be taken care of during US time.

 

[attheedgeofscience]

For those of you in the double super secret working group... how does the data look for those of us that got it from ear infections? DannyBoy is the only one I'm aware of that is on RTG that got it in that fashion.

I would say there is too little data to support anything too concrete in relation to specific etiologies. What can be said is that there appears to be two groups of people: those who experience significant relief and those who experience little when measuring start vs. end improvement (not interim improvements) and the etiologies behind those two clusters can be grouped (and seemed to indicate certain pre-liminary findings)

The purpose of a study would be to have a greater pool of data allowing a clear pattern to emerge in terms of efficacy (and etiology). We also have to recognize that the data we have collected so far is not of the same rigour as that collected in a trial setting.

Also, is there anything I can do to assist? East Coast of the US, so could take some action items that needed to be taken care of during US time.

Thanks for the offer. We will need to see what the immediate future brings in terms of workload; as such there is no timezone issue with this particular project. We will keep you in mind.

Thanks.

 

[Hudson]

I would say there is too little data to support anything too concrete in relation to specific etiologies. What can be said is that there appears to be two groups of people: those who experience significant relief and those who experience little when measuring start vs. end improvement (not interim improvements) and the etiologies behind those two clusters can be grouped (and seemed to indicate certain pre-liminary findings)

The purpose of a study would be to have a greater pool of data allowing a clear pattern to emerge in terms of efficacy (and etiology). We also have to recognize that the data we have collected so far is not of the same rigour as that collected in a trial setting.



Thanks for the offer. We will need to see what the immediate future brings in terms of workload; as such there is no timezone issue with this particular project. We will keep you in mind.

Thanks.

Feel free to hit me up for money or time if it is needed.

 

[Markku]

What would you consider syringing to be if its not trauma of some sort to your ear?
Just curious ?

Trauma of some sort, in my case (since it caused tinnitus), certainly I think it was. But I don't think it was excessive noise exposure. That was my point.

 

[SoulStation]

I see. I always though the syringing was a noisy procedure since so many people have gotten T from it and therefor thought it was noise induced T. So what you are implying is that potassium modulators probably won't have any effect on us who got T from loud noise? Well that sucks

I don't think that's true. Definitely got my t from noise partially and trobalt helped me but I couldn't handle the side effects.

 

[Philemon]

I don't think that's true. Definitely got my t from noise partially and trobalt helped me but I couldn't handle the side effects.

yeah, quite the same for me, i think my T definitely came from too much noise exposure only and even if retigabine is not magical for me as for @Mpt , it's doing great, at least for now ... or maybe a proper study will reveal that it works less well for people like me but that some people from this category are simply outliers for whom it's doing good as well ... for now we can't know

 

[TomKA]

I will start with RTG later today and the cause of my T is otitis media like DannyBoy - so we have a second case of an ear infection induced T

 

[Steve]

The study is pretty small so it can easily be something random. If we can get a much larger study off the ground then we will know an awful lot more, we can see if this is replicated.

 

[David S]

How are studies like this typically conducted? Does ATA have their own medical expertise to conduct this or would they collaborate with somebody else?

Would it be double blind? Would it measure both subjective and objective factors? How many candidates would be needed? What type of T? Severe for at least 6 month?

I would imagine that just getting the right candidates from just one hospital would take a lot of time. Maybe we could start to find candidates here. I might fit the criteria then. I have been prescribed Trobalt but have decided not to try it yet. Maybe that would be a good approach to get candidates fast. Try to gather people that already got it prescribed but are willing to wait a little before they try it. If there are plans to do a more specific pre study here on TT I might consider that as well.

 

[valeri]

Is GSK aware of the results of TT members Retigabine trial?

 

[attheedgeofscience]

Is GSK aware of the results of TT members Retigabine trial?

There has been work ongoing all weekend; some of you may have noticed that I (and other members) have been online "constantly" since Friday.

I do not wish to be too specific about developments right this very minute. There will be follow-up with a number of points of contact tomorrow or Tuesday. Whether we will have something to share before x'mas, I don't know for sure.

But the process we are involved in will take time (please remember that the average clinical trial period from preclinical to end phase-III can easily take 10 years!). Even if we had all the resources in the world available to us (which we don't), a study in itself would take a certain period of time to actually execute before results can be established eg. participants need to actually follow a treatment protocol for a certain duration (needless to say).

When there are developments, we will share them.

attheedgeofscience
21/DEC/2014.

 

[Rube]

There has been work ongoing all weekend; some of you may have noticed that I (and other members) have been online "constantly" since Friday.

I do not wish to be too specific about developments right this very minute. There will be follow-up with a number of points of contact tomorrow or Tuesday. Whether we will have something to share before x'mas, I don't know for sure.

But the process we are involved in will take time (please remember that the average clinical trial period from preclinical to end phase-III can easily take 10 years!). Even if we had all the resources in the world available to us (which we don't), a study in itself would take a certain period of time to actually execute before results can be established eg. participants need to actually follow a treatment protocol for a certain duration (needless to say).

When there are developments, we will share them.

attheedgeofscience
21/DEC/2014.

I would like to give my thanks and appreciation to everyone on team trobalt as well as the trialees. If there is anything the rest of us can do please let us know.

 

[Dr. Nagler]

Let's say ATA agreed to fund a Retigabine study ... or let's say any research group agreed to do such a study.

It may be a silly question, but I wonder how they could do the blinding. I mean, judging from what I've been reading on this board, the side effects of Retigabine are such that those in the treatment arm of the study would likely know that they weren't receiving a placebo. That was the huge flaw in the alprazolam (Xanax) study back in 1993. Those in the Xanax arm pretty much knew that they weren't receiving sugar pills purely by how they felt.

I'm sure that a properly blinded Retigabine study could be developed, but it would require a good bit of thinking and creativity.

Dr. Stephen Nagler

 

[attheedgeofscience]

Let's say ATA agreed to fund a Retigabine study ... or let's say any research group agreed to do such a study.

It may be a silly question, but I wonder how they could do the blinding. I mean, judging from what I've been reading on this board, the side effects of Retigabine are such that those in the treatment arm of the study would likely know that they weren't receiving a placebo. That was the huge flaw in the alprazolam (Xanax) study back in 1993. Those in the Xanax arm pretty much knew that they weren't receiving sugar pills purely by how they felt.

I'm sure that a properly blinded Retigabine study could be developed, but it would require a good bit of thinking and creativity.

Dr. Stephen Nagler

Without thinking too deeply about your question, Dr. Nagler, my immediate response would be: how did Trobalt make it to the market in the first place as a treatment against epilepsy (in a double blind study)?

I suppose that is what you are hinting at with your reference to the Xanax study. I do not know the answer, and as such, I am not bothered by it, because one way or another, I will not be the one who has to deal with the issue (in the end).

Personally, I do not require studies (to always) be double blind (or even single blind). I don't believe in the placebo effect (personally) ie. either the stuff works or it does not, and if I was taking a placebo say - for a pain condition - I am sure I would not notice an effect (just like I am pretty sure a person with severe back pain would notice the difference between Morphine and a pill made of flour). My (simplistic) opinion.

 

[Dr. Nagler]

Without thinking too deeply about your question, Dr. Nagler, my immediate response would be: how did Trobalt make it to the market in the first place as a treatment against epilepsy (in a double blind study)?

You make a good point. Like I said, it might be a silly question. I'm sure there would be a way of doing it, I just couldn't think of it off the top of my head. Good thing I'm not a researcher, huh? Perhaps they might use a placebo that produces some of the same symptoms that Retigabine produces. I dunno.

Anyway, I hope that you and the rest of Team Trobalt are successful in your efforts.

Dr. Stephen Nagler

 

[tomm]

I was not planning on responding to questions concerning pharmacology and efficacy in this thread (or in general) as this is a thread which concerns a study of Trobalt (and not which type of medication will end up more effective and so on). And in any event, it would not be prudent for me to comment on such topics as I do not have a background in medicine or the natural sciences.

However, as is often the case with Internet forums, opinions seem to flourish rather easily. But the following is not an opinion, but a fact...

Earlier on in this thread, I mentioned a new development from a researcher that I had contacted - a development which still remains unpublished:


Within the undisclosed TinnitusTalk-group pursuing the efforts for a study of Trobalt, there has been further communication with the researcher in question. Based on that, I can confirm the researcher's expert opinion that the "modified" version of Trobalt, mentioned above, will in his/her belief be superior to AUT-63. Of course, the work so far relies purely on animal studies, but that was the researcher's estimate at this stage.

Trobalt targets the full Kv7.2-5 range, whereas the above development is specific to Kv7.2/3; it is less toxic and more specific in relation to tinnitus (and epilepsy).

While the above development may have an element of uncertainty associated with it, the following is pretty clear:

1) Trobalt is a drug available on the market at-the-moment.
2) A study can be conducted on the drug - Trobalt - proving (or disproving) its efficacy in relation to tinnitus, in general, or in relation to specific sub-types of tinnitus that initial results of our informal trial may be pointing to.
3) The above can take place regardless of any other development that may - or may not - be occuring within the field of tinnitus research.
4) There is a need for a pharmacological treatment (now).

I can only encourage members of this forum to engage in debate based on facts and well-reasoned opinions rather than speculation.

attheedgeofscience
18/DEC/2014.

Has the paper mentioned by the researcher been published yet ATEOS?

How is the project progressing?

 

[Markku]

I'm not @attheedgeofscience but I can respond to your inquiry @tomm.

Has the paper mentioned by the researcher been published yet ATEOS?

No it hasn't been published yet. We'll announce it the moment it is.

How is the project progressing?

It's going great:

But we can't announce anything in public yet. Quite a bit has been happening behind the scenes however, including some exciting new and unexpected turns. Some key people are still away on holidays, but we should hopefully have something more concrete to say within a month or so.

 

[RaZaH]

You guys are so amazingly proactive about this whole mess , I feel ashamed of just sitting here feeling sorry for myself

 

[Champ]

You guys are so amazingly proactive about this whole mess , I feel ashamed of just sitting here feeling sorry for myself

Just taking it and being involved is doing a lot @RaZaH =)

Being involved in the discussions at all is enough for most people. We just need more and more of us who have tinnitus to get involved!

 

[luigilo]

The secret group intended to prepare a solid report for submission to the ATA if I understood correctly ?

Ps :The forum UI/UX is very well developed

 

[Hudson]

I am patiently awaiting any updates on this! I am very excited about it!

 

[luigilo]

I think this is an issue that is ready to be submitted to the ATA , or other confidential informations from ATA

 

[Steve]

As an announcement of what we are doing with the results...

We have been communicating with the Tinnitus Research Initiative about the informal Trobalt trial on TT. They are very interested in this and very interested in the concept of this kind of informal, internet based trial.

We have given them the results to date and they are going to submit an article summarising the activity to the journal "Expert Opinion on Pharmacotherapy".

We can't stress enough how important it is for all people doing their own trial to complete the new user and update forms. What's happening here is really making a difference, voices are being heard. The more data we have the better the assessment that can be made.

The more "out there" this gets the better we can engage others to progress to potential off label use and potential further trials on a refined version for tinnitus - if it continues to show efficacy.

 

[Dr. Nagler]

As an announcement of what we are doing with the results...

We have been communicating with the Tinnitus Research Initiative ...

Excellent. These folks are the REAL DEAL. I cannot tell you how impressed I am with Team Trobalt's focus and resolve.

Here is a link to TRI's latest newsletter ...

http://www.tinnitusresearch.org/en/news/pdfs/TRI_Newsletter_2914.pdf

Well done, Team Trobalt!

Dr. Stephen Nagler

 

[Hudson]

Excellent. These folks are the REAL DEAL. I cannot tell you how impressed I am with Team Trobalt's focus and resolve.

Here is a link to TRI's latest newsletter ...

http://www.tinnitusresearch.org/en/news/pdfs/TRI_Newsletter_2914.pdf

Well done, Team Trobalt!

Dr. Stephen Nagler

I agree! Their interest in this is very encouraging to say the least. Thank you all for the work on submitting what we have so far to the TRI.

 

[attheedgeofscience]

UPDATE

A manuscript based - in part - on the data submitted by participants of the informal trial of Trobalt (here on the forum) has been submitted by TRI to the pharmacological journal "Expert Opinion on Pharmacotherapy" last week. The manuscript has (also) been read and reviewed by Team Trobalt and is now pending independent peer review with researchers of the journal.

One weakness has been highlighted within the manuscript in relation to the collection of data: points of assessment were not standardized. This essentially means that arbitrary days were chosen for the progress reports that have been filed. This - from a "clinical trial" point of view - is a flaw. Going forward, it would therefore help enormously if participants could report their progress daily or weekly (and if weekly, on the same weekday each time). Just fill out the basic skeleton data (no need to write a whole "novel" each time in the comment section) - it takes less than one minute to do so.

There is plenty of evidence that Kv7.x channel modulators play a role in the treatment of tinnitus (and other neurological diseases). There are currently a number of researchers and pharmas that have "2nd generation" drugs of this type in their pipeline:

SF0034 (www.scifluor.com/our-approach/our-approach-fluoro)
xxx (http://knoppbio.com/research/show.php?2)
yyy (www.audres.pitt.edu/people/tzounopoulos.php)

We will try to track down more information on these developments and share (what we can) in public.

attheedgeofscience
19/FEB/2015.

 

[attheedgeofscience]

In addition, I would like to thank the group of professors behind the pioneering research paper titled "Pharmacodynamics of potassium channel openers in cultured neuronal networks", released online March 25, 2014.

It has come to my attention that the research paper I have previously quoted is now available in its entirety (for free) @:

www.researchgate.net/publication/261220232_Pharmacodynamics_of_posstassium_channel_openers_in_cultured_neuronal_networks

It has also come to my attention that the group of researchers behind the paper (headed by Prof. Moore) have the capability to engage in further research of the drugs mentioned in the paper as well as engage in research of more advanced compounds with a more specific selectivity of the K+ channels (improving both side-effects and potency for tinnitus suppression). As with all basic research done at public institutions, funding is frequently an issue. This also applies in this instance.

attheedgeofscience
28/MAR/2015.

 

[preslys]

Kcnq1-5 (Kv7.1-5) potassium channel expression in the adult zebrafish
http://www.biomedcentral.com/1472-6793/14/1

 

[marqualler]

It has come to my attention that the research paper I have previously quoted is now available in its entirety (for free) @:

www.researchgate.net/publication/261220232_Pharmacodynamics_of_posstassium_channel_openers_in_cultured_neuronal_networks

It has also come to my attention that the group of researchers behind the paper (headed by Prof. Moore) have the capability to engage in further research of the drugs mentioned in the paper as well as engage in research of more advanced compounds with a more specific selectivity of the K+ channels (improving both side-effects and potency for tinnitus suppression). As with all basic research done at public institutions, funding is frequently an issue. This also applies in this instance.

attheedgeofscience
28/MAR/2015.

Is there a preferred method of funding that the researchers would use to receive funding for interested parties? Would setting up a Kick starter a type funding request be appropriate for their needs?

Thanks for doing this important leg work, ATEOS!