Retigabine (Trobalt, Potiga) — Petition to the ATA

[attheedgeofscience]

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?

I appreciate your question/concern. I would say the main question here, however, is not the type of funding, but getting funding in the first place (as well as getting people/organizations to actually look into it). I do not know the exact monetary amounts needed to carry the research forward. I had a look at the acknowledgements within the research paper and it lists three grants from:

1. UNT (EJM, 62313)
2. Once Upon a Time Foundation (EJM, 64301)
3. Charles Bowen Memorial Endowment (GG, #178)

I tried to track down the size of the grants via public information, but I have been unable to do so (and in any event the research was also funded by other means so the above grants would not disclose the "full picture" anyhow). However, for comparison purposes, I also looked into a research grant provided to Prof. Tzounopoulos for a similar type of research:

http://cdmrp.army.mil/search.aspx?LOG_NO=PR093405

As can be seen from the public records, he was granted $920k. I (therefore) doubt the professors behind the research paper "Pharmacodynamics of potassium channel openers in cultured neuronal networks" (Prof. Moore & colleagues) would require more than such a sum of money (for future research).

Now, I would like to bring in a few facts (and realism) to this post. At the time this thread was initiated, TinnitusTalk had some 6000 members in total and roughly 1000 active users (i.e. members who log in once a month or more). For each of the major updates that were done in this thread such as...

www.tinnitustalk.com/threads/retigabine-trobalt-potiga-%E2%80%94-petition-to-the-ata.6896/page-4#post-81060

...I specifically asked the staff of TinnitusTalk to send "alerts" to all active users (so that they were notified of the developments in this thread upon their next log in). Additionally, @Markku spent a considerable effort producing a newsletter to all 6000 members (which was mailed to their private e-mail accounts). Despite these efforts to create awareness and interest among members, the response and willingness to support the initiative has remained close to what is probably best described as "non-existent" - here's why:

1. Out of 6000 members, none volunteered to join Team Trobalt, initially. I had to "hand-pick" members in order to get anyone to join (besides @Steve and @Markku who were already part of the team).
2. The ATA was initially contacted as the organization to assist us with the informal trial i.e. getting a formal study undertaken in order to (hopefully) prove efficacy of Trobalt (and hence move the drug from off to on-label in the treatment of tinnitus). The ATA did respond to our request, but I would not describe their feedback as especially "welcoming" i.e. we were essentially told that we should anticipate self-funding (to some degree) and we would have to submit a formal proposal for the ATA to consider (which would then - probably - take a fair bit of time to process by the SAB). We were also told another "fact" (by a former member of the ATA) we would have to comply with in order to increase our chance of success (of the proposal being approved by the ATA). But I cannot disclose that "fact" in public.
3. Despite many - both public and private-message - pleas to get participants of the trial to complete their progress forms regularly, the end result has been poor in this respect. I estimate that Team Trobalt has invested some 400 hours of our own time (in total). Still, getting a user to just spend one minute per week or per day to fill out the basic skeleton data of the progress forms has been somewhat difficult (for roughly 50% to 60% of the trialees). As late as yesterday, this very fact was actually highlighted by another non-Team Trobalt member:

   i am disappointed that more people have not tried RTG, and that those who do try have not done a good job of reporting their results.

For the reasons above, 1 to 3, it is therefore quite clear that achieving goals within the the tinnitus community itself remains a serious uphill battle (i.e. if we cannot get ourselves - nor the organizations supporting us - to help our own cause, then the mission is over before it even began).

So what can a community do if it cannot help itself? Well, you can try to enlist the help of someone who can! It just so happens that the research into K+ channel modulators not only benefits the tinnitus community, but also other patient groups, such as those with epilepsy and possibly other neurological disease areas e.g. Alzheimer's Disease. Perhaps such communities (or those organizations supporting them) will prove to have more resolve than the tinnitus community (the immediate answer to that should be a "yes" - because it cannot get any worse!).

Team Trobalt is very appreciative of the Tinnitus Research Initiative (TRI). They have been very helpful, understanding, and professional from the very moment @Steve contacted them. They have continuously been prompt in their responses to us - allowing us to make a lot of progress with the data collection process in a short period of time. They have also written a professional manuscript based - in part - on the data collected here on the forum. We are very lucky to have been given a chance to join team efforts with them. Still, we need to ensure that also basic research into pharmacological approaches is maintained (such as that carried out by Prof. Moore's team).

As mentioned in an earlier post, the entire research paper titled "Pharmacodynamics of potassium channel openers in cultured neuronal networks" is now available online (in its entirety and free-of-charge) @

www.researchgate.net/publication/261220232_Pharmacodynamics_of_posstassium_channel_openers_in_cultured_neuronal_networks

Personally, for what it is worth, I would easily rate the research paper, above, as one of the top three most important research papers ever written on tinnitus and pharmacology. The paper is just 8 pages in length, yet conveys a lot of solid information on the drugs investigated. The comparison of the four drugs is there; the comparison of the dosage is there; the pharmacology breakdown in relation to simulated tinnitus activity is brilliantly analyzed and displayed on several different series of charts. And it all pertains to drugs which are currently on the market - and not some future yet-to-be-released drug.

The research was conducted in the lab of Prof. Gross:

http://sustainable.unt.edu/guenter-gross
http://www.researchgate.net/profile/Guenter_Gross

The expert on tinnitus within the team is Prof. Moore:

http://speechandhearing.unt.edu/people/faculty/moore
http://www.researchgate.net/profile/Ernest_Moore2

I know for a fact that funding remains an issue within their line of work. Which can sometimes seem surprising given that the US Armed Forces spends some one billion dollars annually on tinnitus disabilities. With just the tiniest fraction of that amount, the fine researchers, above, could go a long way.

attheedgeofscience
30/MAR/2015.


P.S. I suggest the staff of TinnitusTalk considers if it is worthwhile tweeting and/or sending an alert about this entry.

 

[Martin69]

@attheedgeofscience
ATEOS, thanks for the summary and detailed information.
Perhaps if the US Armed Forces would know about this research paper and the potential effect of these drugs, they would spend this little amount of money (compared to the billions they spend every year) to the research team. I guess the only driving factor is money and benefit - for military, for pharmas, for everyone doing business. So I hope, GSK, other pharmas and the US military will see the benefit of those drugs and do further investigation in this direction.
Thanks again for your immense efforts here. You make a huge difference.

 

[attheedgeofscience]

Perhaps if the US Armed Forces would know about this research paper and the potential effect of these drugs, they would spend this little amount of money (compared to the billions they spend every year) to the research team.

Team Trobalt already has a contact within the Armed Forces (a research professor in otolaryngology). Our understanding from e-mails and phone calls with this contact is that the US Armed Forces prefers to spend resources on psychotherapies (e.g. TRT/CBT) for the treatment of tinnitus.

That does not rule out that other parties within the huge DoD-behemoth may have another opinion on the matter e.g the leadership of the Hearing Centre of Excellence, for instance:

http://hearing.health.mil/AboutUs/LeadershipBios.aspx

But someone has to actually establish the contacts to know that. There is a lot of "talk" on this forum, but very little action...

 

[Martin69]

But someone has to actually establish the contacts to know that. There is a lot of "talk" on this forum, but very little action...

I have no clue how to bring the US Forces to action investigating in potential drugs we poor sufferers here try on a forum. Most people are here seeking help and support and have huge problems going through their day. But I guess you do not mean us sufferers, but someone else.
I agree that probably too much is spent on TRT and CBT instead of a real cure.

 

[attheedgeofscience]

But I guess you do not mean us sufferers, but someone else.

The following is a little story I recall from the past:

That's Not My Job: The Story of Everybody, Somebody, Anybody, and Nobody...

This is a story about four people named Everybody, Somebody, Anybody and Nobody. There was an important job to be done and Everybody was sure that Somebody would do it. Anybody could have done it, but Nobody did it. Somebody got angry about that, because it was Everybody's job. Everybody thought Anybody could do it, but Nobody realized that Everybody wouldn't do it. It ended up that Everybody blamed Somebody when Nobody did what Anybody could have.

 

[nills]

he US Armed Forces prefers to spend resources on psychotherapies (e.g. TRT/CBT) for the treatment of tinnitus.

Of course they do, it is the quickest way to have a file dealt with and out of their hands into the care of some other institution ... dear God please don`t let us try something new and unknown ... we might have to deal with unforeseen circumstances.

 

[kmohoruk]

Thank you for sending this out as a massive post guys, as I didn't even really know that this was going on. One day very soon once I get back into the swing of things and over my H I would then really like to participate with helping our with these new research efforts.

For people with T and H... if we want change to happen then in many way we need to make ourselves known and push for this change ourselves.

 

[ezzy]

What is this all about? I joined the list recently and I havent a clue. YOu need volunteers for some research study? WHere? WIth my tinnitus and vertigo, it's difficult to wade through all the posts to figure this out. Maybe that's true for a lot of us.

 

[SteveToHeal]

The comparison of the four drugs is there; the comparison of the dosage is there; the pharmacology breakdown in relation to simulated tinnitus activity is brilliantly analyzed and displayed on several different series of charts. And it all pertains to drugs which are currently on the market - and not some future yet-to-be-released drug.

Did any of the 4 currently available, report a decrease in t? Only Trobalt to my knowledge is one that actually is having any effect, which is almost imposible to get legally.

 

[valeri]

@attheedgeofscience

Can TRI do anything to involve US army?
I'm by no means an expert but this sort of communication or proposition would have to come from a legit organisation and not from a mere online forum member.
I guess there's s limit how much an average person can do compared to an established organisation.

 

[attheedgeofscience]

Did any of the 4 currently available, report a decrease in t? Only Trobalt to my knowledge is one that actually is having any effect, which is almost imposible to get legally.

If you look at page 6 within the research document, you will find the "concentration-response" curves for each of the four drugs investigated. All four drugs had an effect in this in vitro investigation.

 

[attheedgeofscience]

@attheedgeofscience

Can TRI do anything to involve US army?

I believe TRI has done all they can at this point.

My post, above from yesterday, was "tweeted" and a newsletter will be going out about the continued need for funding. That should create some awareness - hopefully; although much of it reaches "just" the patient group (= us), and not the actual "funding community", so to speak.

 

[attheedgeofscience]

I guess there's s limit how much an average person can do compared to an established organisation.

Is Team Trobalt not made up of "average" people? Did individual members ie. "average persons" of Team Trobalt not contact various researchers and organizations on their own?

Or are we - somehow - "special average" people?

 

[Sound Wave]

One weakness has been highlighted within the manuscript in relation to the collection of data: points of assessment were not standardized.

Sorry if this has already been discussed, but Apple released their open source (!) Research Kit a few weeks back, which has already gained a lot of interest from the research and medical communities. It would not be rocket science at all to use this with our TT studies.

https://www.apple.com/researchkit/

 

[attheedgeofscience]

Thanks again for your immense efforts here. You make a huge difference.

Thank you! And I forgot to add, yesterday, that "Team Trobalt" consists of...

@Markku
@Steve
@Mark McDill
@Zimichael
@marqualler
@attheedgeofscience

...and so it isn't just me doing the work. It's definitely a team effort (I just happen to be the "visible" part of it). The Team Trobalt section on the forum now counts some +500 messages of group correspondence:

Indeed, @marqualler has just joined the team - and so perhaps we will have some interesting developments to share at some point in the future...

And on the sidelines, Team Trobalt is assisted by @Golly and @Mike34 who provide us with expert advice within their fields of expertise whenever specific situations arise. Many thanks!

attheedgeofscience
31/MAR/2015.

 

[Martin69]

...and perhaps we will have some interesting developments to share at some point in the future.

Every piece counts. Hope is what most of us need and keeps us going.
Thanks to the whole Team Trobalt for their efforts.

 

[valeri]

Is Team Trobalt not made up of "average" people? Did individual members ie. "average persons" of Team Trobalt not contact various researchers and organizations on their own?

Or are we - somehow - "special average" people?

So has Team Trobalt contacted US army?

Also it would be nice to give the rest of us some update, it's been months and still not much info.
Apologies if it has been done and I missed it!

 

[attheedgeofscience]

So has Team Trobalt contacted US army?

Well, what does this say (from just two days ago)?

Team Trobalt already has a contact within the Armed Forces (a research professor in otolaryngology). Our understanding from e-mails and phone calls with this contact is that the US Armed Forces prefers to spend resources on psychotherapies (e.g. TRT/CBT) for the treatment of tinnitus.

Team Trobalt has also been reaching out to a key "front figure" of the US-veterans-with-disabilities community (unfortunately without any response in return). We may try a different route using some "inside information" that we will be gathering shortly.

Also it would be nice to give the rest of us some update, it's been months and still not much info.

I don't have more info than the following important update I provided earlier on (which is about a month ago):

www.tinnitustalk.com/threads/retigabine-trobalt-potiga-%E2%80%94-petition-to-the-ata.6896/page-7#post-95890

I have just checked the author account status with the journal "Expert Opinion On Pharmacotherapy" and as far as I can tell the manuscript is still pending independent peer review from two scientists (which is the requirement of any work that is submitted to this specific scientific journal, apparently). How long that process can take, I do not know (but I do know from other researchers that Team Trobalt has been in contact with (e.g. Prof. Tzounopoulos) that such a process may take several months). I can check with TRI to see if they have further information. I can also check with the editor of the journal.

I would like to also mention what I have already said before: The Tinnitus Research Initiative (TRI) is highly committed to engaging in- and facilitating tinnitus research. They are heading the EU-wide TINNET programme for instance...

http://tinnet.tinnitusresearch.net/

...and they have also been more than willing to help TinnitusTalk (and its members) getting projects going (e.g. using data gathered from volunteers of this forum - which is a new way of conducting scientific research that is becoming recognized as being increasingly useful to researchers around the world). However, as I indicated earlier this week, participants of the informal study of Trobalt have not been especially timely in reporting their data (even though it takes just one minute to fill out the basic skeleton data). And without data, there is no project. Simple as that. That's why I decided not to "sugarcoat" it in my summary from Monday (see post further up).

TRI has its own website (needless to say):

www.tinnitusresearch.org

And there is an upcoming conference hosted by TRI also:

http://tri2015.org/

So with that, it truly is difficult to find anything bad to say about TRI.

I would also like to remind you (and others) of previous posts within this thread. As can be seen from the following entries...

www.tinnitustalk.com/threads/retigabine-trobalt-potiga-%E2%80%94-petition-to-the-ata.6896/page-4#post-78731
www.tinnitustalk.com/threads/retigabine-trobalt-potiga-%E2%80%94-petition-to-the-ata.6896/page-4#post-80103
www.tinnitustalk.com/threads/retigabine-trobalt-potiga-%E2%80%94-petition-to-the-ata.6896/page-4#post-81060

...Team Trobalt has been in contact with a number of scientists looking into potassium channel modulator research. I actually would encourage all who read this to take the time and actually read those obtained statements carefully. As can be seen from the 2nd quote in the first of the three listed URLs, above, there are researchers out there looking to conduct really relevant research (i.e. drugs with fewer or even no side-effects and which at the same time are more effective at treating tinnitus). That very statement was obtained from a professor of pharmacology in the United States. I will re-state the quote again here:

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 by ATEOS>'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.

But as can (also) be seen from the statement, above, funding is - and remains - an issue (even though these fine researchers are not exactly asking for a NASA-size budget).

I will also attach an interesting and recently released graduate thesis on exactly this very topic: Trobalt derivatives. [The paper has been shared before on this board, I should mention]

attheedgeofscience
01/APR/2015.

 

[valeri]

@attheedgeofscience



If only we had you as a chairperson of some tinnitus org...our dreams would have come true long time ago!

 

[Aziz Khan]

1. Does this work for all kinds of T?

 

[svintegrity]

I serve on the review board for several peer-reviewed journals. I have also published in a variety of peer-reviewed journals. From my experience, the editor of the journal always gives a deadline to the reviewer for return of the manuscript. Sometimes it is up to eight weeks, sometimes it is much less, depending on the journal. However, not all reviewers follow that deadline, and it can take longer. The editor can choose to wait for the late review or send the manuscript out to another reviewer. If a reviewer is always late with reviews, the editor can choose to remove him/her from the review board. I have never had a manuscript I have submitted go to fewer than three reviewers. If two reviewers agree, the the editor usually goes with the ones in agreement. If it is only sent to two reviewers, the editor may have to serve as a tie-breaker in an area that may not be his/her area of expertise. Once the editor receives the reviews he/she sends the results to the author(s) -- 1)reject 2) accept with revisions, or 3) accept. Most reviewers are quite ruthless with their comments, and some reviewers can tell who submitted the manuscript simply by the content and references. It is not always as "blind" as thought. It is quite rare to have a manuscript accepted outright for publication without revisions. If a manuscript is rejected, it could be because it is not a good fit for that specific journal, it could be poor quality research, or just poorly written. In the cases where revisions are made, the editor re-submits the manuscript to the same reviewers. After the acceptance of a manuscript, it can take still take several months until publication.

 

[sakrt]

Researchers get PLENTY of funding - in the millions. What's not disclosed is:
1. Who are the sponsors or investors who promote these Drugs/Devices - within USA or foreign?
2. Why not full transparency to the public?
3. Notice the ambiguous terminology researchers often use- "Independent Peer Review" of researchers who only test a certain number of unknown subjects (without full disclosure of other contradictions or medical issues).
4. FDA in USA has become more lax in requirements. Why? Do they receive "contributions" from Pharmaceutical companies? FDA only monitor "clinical trials" - Not current or later issues of any drug(s) or devices (e.g. Cochlear Implants). Full disclosure on serious side-effects/outcomes are NOT usually informed, until it's too late when MANY sufferers come forward. The Drug/ prescription "info" packets, sure are user-friendly, Hm? In 5 pt. font size & 4 pgs+ long that an average person usually cannot follow. (Carefully written by lawyers).
5. I agree with "AttheEdgeofScience" that participants should report their progress daily or weekly (and if weekly, on the same weekday each time). For EVERY product or devices on the market on an annual basis. Why not?
6. If you ask the Medical Commissioner for the raw data to check the validity of any Researcher's "Abstract" or "Publication". It's not available. Why? All that funding and no-one questions if they were truly ethical or valid, and possibly biased. The data should be saved for later purposes and available to the public- but they hide or destroy them. Questionable, isn't it?

 

[Steve]

Researchers get PLENTY of funding - in the millions. What's not disclosed is:
1. Who are the sponsors or investors who promote these Drugs/Devices - within USA or foreign?
2. Why not full transparency to the public?
3. Notice the ambiguous terminology researchers often use- "Independent Peer Review" of researchers who only test a certain number of unknown subjects (without full disclosure of other contradictions or medical issues).
4. FDA in USA has become more lax in requirements. Why? Do they receive "contributions" from Pharmaceutical companies? FDA only monitor "clinical trials" - Not current or later issues of any drug(s) or devices (e.g. Cochlear Implants). Full disclosure on serious side-effects/outcomes are NOT usually informed, until it's too late when MANY sufferers come forward. The Drug/ prescription "info" packets, sure are user-friendly, Hm? In 5 pt. font size & 4 pgs+ long that an average person usually cannot follow. (Carefully written by lawyers).
5. I agree with "AttheEdgeofScience" that participants should report their progress daily or weekly (and if weekly, on the same weekday each time). For EVERY product or devices on the market on an annual basis. Why not?
6. If you ask the Medical Commissioner for the raw data to check the validity of any Researcher's "Abstract" or "Publication". It's not available. Why? All that funding and no-one questions if they were truly ethical or valid, and possibly biased. The data should be saved for later purposes and available to the public- but they hide or destroy them. Questionable, isn't it?

People are trying to change the way the system works, to get all trials registered and always get full reports. See this website for more detail http://www.alltrials.net

@svintegrity My partner recently had an experience of the timeframes involved. Her article was accepted with minor revisions (for a gerontology journal) and she was given 6 months to complete them. By the time it goes to print it'll be a year since the initial submission.

 

[svintegrity]

@Steve That has been my experience too. Usually 9 months to a year from time of submission to publication. And that is with minor revisions. With major revisions, it will take longer. I once had a manuscript that took two years from submission to print. Six months for revisions is very generous. Congrats to your partner for her work!

 

[sakrt]

USA's Food & Drug Administration (FDA) stated- they ONLY monitor "Trial Tests"/subjects for abstracts or publications for the short-term (e.g. 3 mos. to a year) - YES. Perhaps in UK, it's different?
Post-Trials & onwards, outcomes, unexpected side-effects, updates, monitoring those subjects -LONG TERM? NO. Unless something seriously drastic happens involving many patients, otherwise it's paid off by pharmaceutical companies without going to Trial to avoid public knowledge. They simply just add a few extra words in their (5 pt font) information packets one gets with their prescriptions. You don't see *WARNING* like on cigarette cartons, hm? Realistically, the average customer, especially seniors do not fully (if at all) comprehend the scientific medical jargon with the lovely elaborate graphics of molecular structure diagrams.

It's a very simple request to provide transparency to the public of LONG-term outcomes of all Drugs and devices. Isn't it. If not, why not? (Am I missing something, I'm unaware of?)
If one asks FDA today, the answers are often "Do not know" because the "funds" have stopped after the Pre-Trial test/publications. Researchers continue on to the next new funded "trial-test(s)" which is a prerequisite to "pass" a drug to go on the market. I agree the (little) people need to "change the way the system works". However, its the wealthy conglomerate manufacturers who control it all. $$$

 

[valeri]

@attheedgeofscience
@Markku

I've emailed GSK today, so now we just hope for some reply.
Even though I called many times I couldn't get any further than getting to write an email that they will forward to the relevant department.
I would have preferred some name at least but it just obviously doesn't work like that.
Will keep you posted.

 

[valeri]

@attheedgeofscience

Are there any brief statistics of RTG trial?

 

[attheedgeofscience]

@attheedgeofscience

Are there any brief statistics of RTG trial?

See this: www.tinnitustalk.com/threads/retigabine-trobalt-potiga-%E2%80%94-petition-to-the-ata.6896/page-5#post-82727

...and the paper on Trobalt and other K+ channel openers (Prof. Moore and colleagues).

 

[valeri]

See this: www.tinnitustalk.com/threads/retigabine-trobalt-potiga-%E2%80%94-petition-to-the-ata.6896/page-5#post-82727

...and the paper on Trobalt and other K+ channel openers (Prof. Moore and colleagues).

Can this be provided to GSK?
I'm not sure if this the proper format though.

 

[attheedgeofscience]

Can this be provided to GSK?

This is a public forum. The information here is available for all to share and distribute.

I'm not sure if this the proper format though.

I am honestly not sure what you mean. Are you referring to the paper by professor Moore or the statistics? Or are you referring to the fact that the data collected in the trial was done via the Internet? Or are you referring to the file format of the statitics? Or something else?