Retigabine (Trobalt, Potiga) — Petition to the ATA

[valeri]

I still think our sample size in the Retigabine trial is too small and too "young" to get serious attention in the halls of GSK, etc.

Sure it's small but that's because of the supply issue or doctors unwilling to prescribe it.
You personally experienced how difficult it is to obtain this drug and due to that you didn't get a chance to give it a proper go.

I'm also thinking of that poor guy Craig who, maybe, would still be with us if he had a chance to try it.

 

[rtwombly]

Philemon gave an excellent summary. Anybody who was able to get a supply and tolerate the side effects and got above 600mg (sorry Zimichael, just trying to sum up) had a noticeable reduction in their tinnitus. That's something like 7 or 8 people. There would be much more data if the drug was a) more readily prescribed and b) covered by health insurance in the US and UK (or just cheaper, but that's not likely to happen any time soon). To get "b" to happen there would have to be double-blind large scale clinical evidence of efficacy for tinnitus, but "a" could be helped by much less stringent and time-effective testing.

 

[RaZaH]

Isnt the main issue still open ?
That is , does this have a permanent effect for anyone else than @Mpt ?
Remains to be seen.

 

[valeri]

@SteveToHeal

Great idea about the film, even a 5 minute clip that can go on Facebook would be a good start.
We should not underestimate the power of social media at this time and age, it's a powerful tool to get public attention.

@amandine
I disagree about involving hearing aid manufacturers, at the end of the day it's not in their interest for a cure to ever be found, either for tinnitus or hearing loss. Too much money to loose.
Very sad but unfortunate truth

Out best bet is getting pharma industry interested, anything that can make more money for someone is more attractive than shutting the door because people are getting cured.
Hmmmm....modern medicine has come a long way!

 

[valeri]

http://news.optuszoo.com.au/2014/11/20/stars-fall-silent-for-ebola-video/

We need something like this too!

I can't believe that with so many musicians with tinnitus no one ever did anything about it!

WAITING.....

@amandine
This could be your field of expertise

 

[dan]

Ok, I'll make it simple for you guys.
Contact the OHSU (Oregon Health and Science University).
They have (or had) a large tinnitus research department.
Or we can contact any other major research university like Michigan State, or Berkley California. These institutions have the funds for doing independent clinical trials, as big as 500 trialees.
For example, a few years back, the drug Acamprosate which was already approved for alcoholism treatment, was trialed by OHSU which was also funded by the ATA.
We have the information right here on TT!
Our forum member @Louise had actually got a response from them -

I asked OHSU about the results of a trial they were doing for Acamprosate helping T. Here's the email I got.....

Louise,
Thanks for asking about the study. We have finished it and are writing it up for publication. The results have been presented in preliminary form at the International Tinnitus Society meeting last year in Brazil. We could find no difference in the effectiveness of Acamprosate compared to placebo in an extended, very carefully done study.

Billy Martin

William Hal Martin, Ph.D.
Professor of Otolayrngology/Head & Neck Surgery
Director, OHSU Tinnitus Clinic

So as you can see @jchinnis , the ATA in fact has done drug studies before.
I think you are thinking a drug "trial" in the sense of going from pre-clinical model to market, and I agree that is huge and beyond the scope of the ATA.
However, for a drug which is already on the market, but has the potential to treat tinnitus, it is a realistic goal. Whether Retigabine would be proven as a cure, or as a treatment to alleviate symptoms, will be up to the trial results.

Here is the thread that discusses the Acamprosate trial on TT
https://www.tinnitustalk.com/threads/acamprosate-campral.394/

@Dr. Nagler , lets be on the same team here.
Here are some of your wise words from that thread.

"By the way, there was a very carefully controlled meticulous study of acamprosate conducted by the highly-regarded OHSU group in Portland last year. The study found absolutely no therapeutic benefit in the treatment of tinnitus for acamprosate over placebo. Publication is pending.

Still, no downside in trying. But it is good to go into these things with your eyes open, no?

smn"
-----------------

"But when Dr. Billy Martin puts something down in writing, it is worthy of attention. Dr. Martin is universally respected in the clinical, research, and academic tinnitus communities. Here is what he wrote to one of the participants on this board:

Louise,
Thanks for asking about the study. We have finished it and are writing it up for publication. The results have been presented in preliminary form at the International Tinnitus Society meeting last year in Brazil. We could find no difference in the effectiveness of Acamproate compared to placebo in an extended, very carefully done study.

Billy Martin

William Hal Martin, Ph.D.
Professor of Otolayrngology/Head & Neck Surgery
Director, OHSU Tinnitus Clinic

So skepticism is good, but it helps to know your sources. Billy Martin has been a colleague and close friend of mine for more than a decade now. If he says something, you can take it to the bank.

All that aside, I wish you great success with your acamprosate.

smn"
------------------------

I would also like to ask members to refrain from branching out into other awareness areas (tinnitus movies/plays/broadway/concerts) and concentrate on pushing for a Retigabine trial for now. Please lets not lose our aim here.

Thank you to all.

 

[Telis]

I don't get it. Why is there a push to trial retigabine? Won't this take years? Aut00063 results will be in by that time and the drug possibly on the market.

 

[valeri]

@dan
Yes I agree, we should stick with this aim and maybe start another thread with other ideas.
If @Markku want to move my post elsewhere that's fine
It was just something I got in my email this morning.

 

[valeri]

I don't get it. Why is there a push to trial retigabine? Won't this take years? Aut00063 results will be in by that time and the drug possibly on the market.

It shouldn't take years since the drug is already on the market.
It's just a matter of proving it's efficiency for tinnitus and providing easier access to it.

No one is questioning AUT063, it's just that NOW we may have something to help us until something better is available.

 

[dan]

I don't get it. Why is there a push to trial retigabine? Won't this take years? Aut00063 results will be in by that time and the drug possibly on the market.

....and what if it won't? do you want to wait and do nothing until then?
....also I'm sure that a Retigabine mini trial will be much quicker than phase 2 and 3 for Autifony.

 

[Telis]

....and what if it won't? do you want to wait and do nothing until then?
....also I'm sure that a Retigabine mini trial will be much quicker than phase 2 and 3 for Autifony.

I figured this was all pretty much in progress already with aut00063. Won't we know if autifony is successful within a 12 to 18 months? And if this drug is successful could this data not be used (instead of a whole new trial with retigabine) to convince the medical community to treat tinnitus with retigabine until aut00063 is released? And if there is very little to no success with aut00063 maybe retigabine isn't the answer and is not worth pursuing on a large scale.

 

[dan]

I figured this was all pretty much in progress already with aut00063. Won't we know if autifony is successful within a 12 to 18 months? And if this drug is successful could this data not be used (instead of a whole new trial with retigabine) to convince the medical community to treat tinnitus with retigabine until aut00063 is released?

yes we will know if aut63 is successful within 12-18months, but I doubt this data can be used for retigabine. the only way to convince is to do a trial.
even if autifony shows success, having another drug for tinnitus can't hurt.
just like epilepsy patients have several drugs to choose from, so should T patients - as we know from expeerience, one person may respond better to one drug than another. also, other drug companies can then take retigabine and improve it. but first we need that "tinnitus label" on the box.

 

[jchinnis]

@dan, I'm very familiar with drug-related research sponsored by the ATA, as I am with Billy Martin's work. My advice is just to call this a petition for a retigabine study and not a retigabine trial. The word trial carries with it a lot of unintended meaning.

 

[dan]

@dan, I'm very familiar with drug-related research sponsored by the ATA, as I am with Billy Martin's work. My advice is just to call this a petition for a retigabine study and not a retigabine trial. The word trial carries with it a lot of unintended meaning.

Yes I agree since you put it that way.

 

[Dr. Nagler]

@attheedgeofscience posted [in part]:

Now, I am sorry to potentially be the party breaker here, but I only engaged in the dialogue with the professor of pharmacology because of your own request for a petition, and because @Dr. Nagler politely "tasked" me with the job of writing a description of the mechanism-of-action of Trobalt in relation to tinnitus. Being the competent person I am, I immediately realized that it would not be prudent for a "finance person" to write such a mechanism-of-action. And certainly not for a formal petition requesting a study on humans, no less! So what did I do? I decided to attempt to get a written statement from the best of the best - a professor of pharmacology who co-authored a recent paper on tinnitus and potassium modulators, specifically ... I didn't request this workload placed upon me. I am just delivering the hard facts.

.............

Thank you for going to all this trouble. I appreciate it.

I am just looking for a couple of sentences summarizing what is felt to be the drug's mechanism of action and the rationale behind its proposed use in tinnitus. To be honest with you, I do not think this petition is going anywhere. It likely won't even get off the ground. Like @Markku said, "I've seen tinnitus petitions before, and pretty much all of them have failed. I have never seen a tinnitus petition gather more than a handful of signatures. This is the sad reality."

Anyway, I volunteered to help work on the wording. Waste of both of our times, if you ask me. My apologies for roping you into it.

Dr. Stephen Nagler

 

[cullenbohannon]

@jazz thanks for that, And @attheedgeofscience thanks for the effort and keeping us informed. I dont quite know what to make of this stuff. There is a paper by Dr.Large, i think dan posted it already , but he seems to think they do know what the MOA is. The paper was written in 2012.

@Dr. Nagler this is the first few sentences of the summary. I should add the Dr.Large that coauthored this is the CEO of autifony.

The mechanism of action of retigabine (ezogabine), a first-in-class K+channel opener for the treatment of epilepsy

1. Martin J. Gunthorpe1,
2. Charles H. Large2and
3. Raman Sankar3

The pharmacologic profile of retigabine [RTG (international nonproprietary name); ezogabine, EZG (U.S. adopted name)], is different from all currently approved antiepileptic drugs (AEDs). Its primary mechanism of action (MoA) as a positive allosteric modulator of KCNQ2–5 (Kv7.2–7.5) ion channels defines RTG/EZG as the first neuronal potassium (K+) channel opener for the treatment of epilepsy.

http://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2011.03365.x/full

Here is a short review of what an allosteric modulator is if anyone is interested. http://en.wikipedia.org/wiki/Allosteric_modulator

 

[jazz]

@cullenbohannon Thank you! Thank you! I was not aware of that article; this thread is very large and it's easy to get lost. The article's date is 2012 so that's after the reference I published.

Perhaps @Dr. Nagler will now reconsider.

 

[attheedgeofscience]

@attheedgeofscience posted [in part]:

Now, I am sorry to potentially be the party breaker here, but I only engaged in the dialogue with the professor of pharmacology because of your own request for a petition, and because @Dr. Nagler politely "tasked" me with the job of writing a description of the mechanism-of-action of Trobalt in relation to tinnitus. Being the competent person I am, I immediately realized that it would not be prudent for a "finance person" to write such a mechanism-of-action. And certainly not for a formal petition requesting a study on humans, no less! So what did I do? I decided to attempt to get a written statement from the best of the best - a professor of pharmacology who co-authored a recent paper on tinnitus and potassium modulators, specifically ... I didn't request this workload placed upon me. I am just delivering the hard facts.

.............

Thank you for going to all this trouble. I appreciate it.

I am just looking for a couple of sentences summarizing what is felt to be the drug's mechanism of action and the rationale behind its proposed use in tinnitus. To be honest with you, I do not think this petition is going anywhere. It likely won't even get off the ground. Like @Markku said, "I've seen tinnitus petitions before, and pretty much all of them have failed. I have never seen a tinnitus petition gather more than a handful of signatures. This is the sad reality."

Anyway, I volunteered to help work on the wording. Waste of both of our times, if you ask me. My apologies for roping you into it.

Dr. Stephen Nagler

Not really a problem, Dr. Nagler. As such, my comments were not really aimed at you - or anyone in particular for that matter.

I am just letting this board know that people at the professor-level would not be comfortable making a statement about Trobalt's potential for suppressive effects on tinnitus. Research on humans is missing, and so making a statement would be difficult (I guess). I should mention, however, that I did ask the professor, yesterday, for either "a speculated- or a known- mechanism-of-action."

I have not given up. I have engaged another two professors today. Hopefully, they will respond. What the response will be, I don't know. The response from yesterday did surprise me slightly, I must admit.

My main "concern" is that some people on this board seem to think that there are hard facts out there on Trobalt and tinnitus - and indeed there are. But none of these relate to humans - to the best of my knowledge, at least.

Whatever happens, I will do a post in the original thread about the ATA-petition itself. Or @Markku will.

 

[attheedgeofscience]

@jazz thanks for that, And @attheedgeofscience thanks for the effort and keeping us informed. I dont quite know what to make of this stuff. There is a paper by Dr.Large, i think dan posted it already , but he seems to think they do know what the MOA is. The paper was written in 2012.

Thanks!

I am aware of the paper. And indeed we already have a mechanism-of-action from the professor's co-authored research paper itself (not the paper by Dr. Large):

A novel class of drugs – potassium (K+) channel openers or activators – has recently been shown to cause anticonvulsive and neuroprotective effects by activating hyperpolarizing K+ currents, and therefore, may show efficacy for treating tinnitus. The present results highlight the notion of re-purposing the K+ channel activators for reducing hyperactivity of spontaneously active auditory networks, serving as a platform for these drugs to show efficacy toward target identification, prevention, as well as treatment of tinnitus. Trobalt is part of this novel class of drugs.

But for a petition like this, the mechanism-of-action needs to be "anchored" with someone of sufficient competency. I cannot just copy-&-paste a few lines, haphazardly. This needs to be done right.

 

[Dr. Nagler]

@cullenbohannon Thank you! Thank you! I was not aware of that article; this thread is very large and it's easy to get lost. The article's date is 2012 so that's after the reference I published.

Perhaps @Dr. Nagler will now reconsider.

What am I supposed to reconsider? I volunteered to help with the wording. I'm still willing to help with the wording. I think the petition isn't going anywhere. I still think the petition isn't going anywhere. But I'm willing to try. So what's to reconsider?

What I am waiting for are the anecdotal data from this board. I want to know how many people here have taken Retigibine in the hopes of achieving tinnitus relief, and how many of those have achieved what they consider to be substantial relief as a result of taking the drug. Add to that how many here have taken Retigibine in the hopes of achieving tinnitus relief, but stopped the drug because of its side effects. Without those numbers, any petition emanating from this board would be meaningless. And, please, I don't want to be pointed to a series of posts. Just give me the numbers. Also, since the petition will go out under @Markku's name, he will have to agree that the numbers are an accurate reflection of the anecdotal experience here on Tinnitus Talk.

Also I'd like to know when Tinnitus Talk was founded.

Dr. Stephen Nagler

 

[jazz]

Also I'd like to know when Tinnitus Talk was founded.

I believe it was in March, 2011. But you can ask Markku for all details.

 

[Dr. Nagler]

But for a petition like this, the mechanism-of-action needs to be "anchored" with someone of sufficient competency. I cannot just copy-&-paste a few lines, haphazardly. This needs to be done right.

I agree. It has to be done right. But it also has to be done simply. The petition is going to be an appeal to an ATA Board of Directors comprised mostly of lay people. If they like the idea, they can task their Scientific Advisory Committee with digging out the details.

Dr. Stephen Nagler

 

[Christian78]

I agree. It has to be done right. But it also has to be done simply. The petition is going to be an appeal to an ATA Board of Directors comprised mostly of lay people. If they like the idea, they can task their Scientific Advisory Committee with digging out the details.

Dr. Stephen Nagler

Is there someone who know these questions and how they are done legally? I meant on advice from a person who knows these things? Do you know someone?

 

[Dr. Nagler]

Is there someone who know these questions and how they are done legally? I meant on advice from a person who knows these things? Do you know someone?

This isn't a legal issue.

The drug has already been approved for use in epilepsy.

Dr. Stephen Nagler

 

[valeri]

I am just looking for a couple of sentences summarizing what is felt to be the drug's mechanism of action and the rationale behind its proposed use in tinnitus.

Dr Nagler who in your opinion would be the best person to provide the above information?

Does it even have to come from a person or valid scientific papers would do the job?

As I said before there are many smart people on this board, but when it comes to knowing tinnitus world inside and out no one can beat you.
Your help and support is very appreciated.

 

[rtwombly]

What I am waiting for are the anecdotal data from this board. I want to know how many people here have taken Retigibine in the hopes of achieving tinnitus relief, and how many of those have achieved what they consider to be substantial relief as a result of taking the drug. Add to that how many here have taken Retigibine in the hopes of achieving tinnitus relief, but stopped the drug because of its side effects. Without those numbers, any petition emanating from this board would be meaningless. And, please, I don't want to be pointed to a series of posts. Just give me the numbers. Also, since the petition will go out under @Markku's name, he will have to agree that the numbers are an accurate reflection of the anecdotal experience here on Tinnitus Talk.

Let me explain. No, there is too much. Let me sum up.

@Johno -- some improvement, improvement sustained after temporary withdrawal from the drug
@SoulStation -- slight improvement, currently withdrawing due to side effects
@Viking -- slight improvement, withdrew due to (pre-existing?) kidney condition
@Christian78 -- significant improvement despite many side effects
@Bogdan -- significant improvement
@Hengist -- withdrew due to side effects
@Mpt -- practically cured, sustained benefit after fully withdrawing from drug
@Zimichael -- super-chronic case; no improvement, withdrew due to supply problems, conflict in scheduling with dental surgery
@Freddie -- decided not to start treatment in hopes of enrolling in Autifony trial
@undecided -- significant improvement, many side effects
@locoyeti -- significant improvement
@Danny Boy -- significant improvement
@NGC891 -- super-chronic case; just started, has not updated
@Philemon -- just started
@Juan Carlos -- just started, slight improvement
@Ricardo -- "cured" (his quotations) but suffered renal failure, withdrew quickly and tinnitus returned within three weeks; no previous history of kidney problems

@Lep -- withdrew due to side effects, tried again months later, no improvement, remained at low dose due to side effects

Except for Lep's saga, that is all from the User Experiences thread.

You can see just from that brief summation that it is far from a clear case, but there is certainly something going on. I should add that anybody you see in that list who was able to increase their dosage to > 600mg reported at least a slight improvement (post if I'm wrong, please). I believe even SoulStation had some improvement before deciding that his side effects, combined with Ricardo's experience, made it not worth it.

So, interestingly, we've had two people cured and two people who sustained the benefits of their usage after withdrawing from the drug. Unfortunately, they are not the same people. Mpt was cured and sustained, Johno got some improvement and sustained, and Ricardo was cured and did not sustain. We have discussed already Ricardo's case. He had to withdraw rapidly from Trobalt due to his renal failure, so it seems reasonable to conclude that his brain had not had time to consolidate the homeostatic adaptation that would have allowed him to sustain his benefit. He deserves our sympathy twice over for having been slapped by the front and the back hand of misfortune.

All things considered, here's how I run the numbers.

Total participants: 17
Participants who withdrew before 600mg (dosage considered minimal for epileptics): 3 (Viking, Hengist, and Lep)
Participants who have not yet reported after being >= 600mg for at least one week: 4 (Freddie, NGC891, Philemon, Juan Carlos)

Sub-total excluding the above: 10
Participants in the sub-group reporting no improvement: 1 (Zimichael)
Participants in the sub-group reporting slight improvement: 1 (SoulStation)
Participants in the sub-group reporting some improvement: 1 (Johno)
Participants in the sub-group reporting significant improvement: 5 (Christian78, Bogdan, undecided, locoyeti, Danny Boy)
Participants in the sub-group reporting complete improvement (practically cured): 2 (Mpt, Ricardo)

Total participants in the sub-group reporting some or greater improvement: 8

Participants who retained improvement after withdrawing completely from retigabine: 2 (Mpt, Johno)
Participants experiencing major short-term side effects (continual interference in day-to-day life) that went away after discontinuing retigabine: 6 (Hengist, Lep, Zimichael, SoulStation, Christian78, undecided)
Participants experiencing major long-term side effects (with good reason to attribute to retigabine use): 1 (Ricardo)

And a further summation:

Total participants reporting after taking 600mg for at least 1 week: 10
Total participants of that group reporting benefit: 9
Total participants reporting major long-term side-effects: 1

Hopefully Ricardo will be given a clean bill of health. To me, these are pretty fantastic numbers. They are tricky because the actual stories are so much more complex, but if you want to know how many people experienced noticeable improvement in their tinnitus after increasing to a minimal therapeutic dose, it's 9/10. How many think it was worth the side effects? More like 7/10 (excluding Zimichael who had no improvement, SoulStation due to major short term side effects and Ricardo).

Hope this is useful.

 

[Dr. Nagler]

Dr Nagler who in your opinion would be the best person to provide the above information?

Does it even have to come from a person or valid scientific papers would do the job?

As I said before there are many smart people on this board, but when it comes to knowing tinnitus world inside and out no one can beat you.
Your help and support is very appreciated.

This is becoming too much of a project.

I sincerely appreciate @attheedgeofscience's efforts as well everyone else's. But I will take care of the mechanism of action part myself.

What I refuse to do myself is come up with a one or two sentence unambiguous summary of the anecdotal data generated by this board. So I will leave you all to present it to @Markku and let him decide, since Tinnitus Talk is his board.

Dr. Stephen Nagler

 

[valeri]

@rtwombly

Thank you for gathering all that info, results are maybe not a clear cut but there is definitely some evidence that trobalt can provide various degrees of relief.

 

[Dr. Nagler]

@rtwombly

Thank you for gathering all that info, results are maybe not a clear cut but there is definitely some evidence that trobalt can provide various degrees of relief.

In my opinion that will not cut it for our purposes. The petition must indeed present a clear cut summary of the anecdotal experience on this board. Absent that, it does not have a chance in the world of garnering any attention.

Anyway, I'm going to back off until you all come up with something that @Markku is willing to put his name to.

As I said earlier, I'll take care of the mechanism of action piece.

Dr. Stephen Nagler

 

[jazz]

What I am waiting for are the anecdotal data from this board. I want to know how many people here have taken Retigibine in the hopes of achieving tinnitus relief, and how many of those have achieved what they consider to be substantial relief as a result of taking the drug. Add to that how many here have taken Retigibine in the hopes of achieving tinnitus relief, but stopped the drug because of its side effects.

I'm sure Markku can help you with this information. He has the list and you can crunch the numbers. It should not take long, and it will give you the information you need.

And thank you for volunteering to help with the MOA wording.