AM-101 TACTT1 Results Released

[CathodeRaySound]

No problem. It is good we get to know each other better. CRT should not give up

Although AM-101 is no longer viable for me, I am definitely going to try other routes for treatment. Giving up is for people that has met their conclusion with death. Quite frankly, I am no where near that stage yet. If you're not dead, you keep moving, that's the property of life.

 

[Rube]

Although AM-101 is no longer viable for me, I am definitely going to try other routes for treatment. Giving up is for people that has met their conclusion with death. Quite frankly, I am no where near that stage yet. If you're not dead, you keep moving, that's the property of life.

awesome statement.whats next?

 

[attheedgeofscience]

AM-101 treatments due to him neglecting his own aforementioned agreements (which I should have requested in writing).

I am not a laywer, but the responsibility of having the agreements in writing lies with the clinical trial doctor/centre (ie. there are specific criteria of minimum information exchange that they must provide to you - the patient - in writing). He has the burden of proof of what was agreed (ie. you are the "weak party").

The fact that the specific clinical trial centre in question may, or - may not - have a self-made policy of regulations in place, is irrelevant. It is not for him, her, or "it" to decide what rules to enforce in the given situation. If they have specific rules in place (which deviate from the norm) then it is their reponsibility to make you aware of that (again their burden of proof).

So here's what I would do. I would contact the clincial trial centre in question (in writing) asking for the reasons why you were rejected; they have an obligation to respond. Make them aware that you would still like to be considered a candidate for treatment (also). If they don't respond within 48h, send them a reminder that you will be considering legal counsel within the next 24h if they don't get their "act together". Threatening with legal alternatives is not a crime. It will keep them on their toes (especially in the US).

As a comparison, you are in far better position than I was when I had to deal with a loss of USD 13,000,- from my 2nd stem cell treatment in China. At least in the US there is a rule of law in place. By the time I had left China, it was too late...

 

[CathodeRaySound]

@Rube

With AM-101 out of the question, I am going back to the drawing board - tinnitus is not a disease it is a symptom. I will slowly but surely tackle every possible root of my symptom. Through deduction hopefully I can reach a probable conclusion, my recent MRI shows no abnormalities in my brain, I do have TMJ so maybe that is a possible area to look at, I also have ETD, and chronic sinusitis, which might also play a role in my tinnitus, I also have a bad back from boxing and MMA which might contribute to a compressed nerve or something...at the end of the list, if all else fails I can try Retigabine. What I am counting on the most is the future of regenerative medicine, in the best case scenario, I can gather up enough funds within the next years for whatever medical technology has to offer by then. Currently I am a psych student, if everything goes to plan I will be going to medical school in the next year or two, but my tinnitus condition is starting to make me want to pursue something in the regenerative medicine industry as it is extremely promising. If current/near future treatments are lacking in efficacy, I feel like I am obligated to somehow contribute towards a cure now that I am suffering myself and after meeting so many people on here worse off than I am with tinnitus. Even if my tinnitus somehow "disappears", I will always remain a member of this community. I truly believe the time will come soon enough when we can all throw a huge Tinnitus-Talk party for the cure of tinnitus, until then we all need each other, cause no one else will understand what we go through.

 

[CathodeRaySound]

I am not a laywer, but the responsibility of having the agreements in writing lies with the clinical trial doctor/centre (ie. there are specific criteria of minimum information exchange that they must provide to you - the patient - in writing). He has the burden of proof of what was agreed (ie. you are the "weak party").

The fact that the specific clinical trial centre in question may, or - may not - have a self-made policy of regulations in place, is irrelevant. It is not for him, her, or "it" to decide what rules to enforce in the given situation. If they have specific rules in place (which deviate from the norm) then it is their reponsibility to make you aware of that (again their burden of proof).

So here's what I would do. I would contact the clincial trial centre in question (in writing) asking for the reasons why you were rejected; they have an obligation to respond. Make them aware that you would still like to be considered a candidate for treatment (also). If they don't respond within 48h, send them a reminder that you will be considering legal counsel within the next 24h if they don't get their "act together". Threatening with legal alternatives is not a crime. It will keep them on their toes (especially in the US).

Alternatively, and after all options are exhausted, you can also choose to blackmail the doctor in question by basically telling him: "If you don't do what I say, I will go public with my story and spread rumours about your name all over the Internet; you want that?". Obviously this kind of stuff should not be done in writing - needless to say...

As a comparison, you are in far better position than I was when I had to deal with a loss of USD 13,000,- from my 2nd stem cell treatment in China. At least in the US there is a rule of law in place. By the time I had left China, it was too late...

I am extremely sorry for what the Chinese clinic put you through, I would steer clear of China, but I do understand they're leading the world in many aspects of future medicine. From what I remember, the doctor did mention the fact that it is usually recommended for his patient going through an intratympanic injection should have a driver; however, he did say there are exceptions, for this reason, we discussed taxi rides and hotel rooms, if not why would he have mentioned this? I also specifically stated I will not have anyone drive me because of our taxi/hotel decision, and there were no disagreements following this statement, but only two weeks after on the injection day did he have any objections. At this point without any documentation it really comes down to "he said she said", I will take your advice and email them asking for the exact reasons why I am being rejected, and that I would still like to remain a candidate for the trial. However, with Auris even telling me that, "if the doctor doesn't feel comfortable there's nothing we can do" I don't know if it is even worth bothering them more about it...I'm pretty split, I feel like I am certainly in the right, but at the same time it all seems so futile at this point.

 

[attheedgeofscience]

I am extremely sorry for what the Chinese clinic put you through, I would steer clear of China

Don't worry about me. I am an adult (= +30 years old).

At this point without any documentation it really comes down to "he said she said"

That is (unfortunately) often the case. However, as I say, there are minimum requirements of information exchange (in writing) that need to take place. If that did not happen, burden of proof lies with the "good doctor"...

I also specifically stated I will not have anyone drive me because of our taxi/hotel decision, and there were no disagreements following this statement

State that in your e-mail. And see what they respond.

I will take your advice and email them asking for the exact reasons why I am being rejected, and that I would still like to remain a candidate for the trial.

Legally, you need to let them know your intentions. Agreed.

 

[attheedgeofscience]

From what I remember, the doctor did mention the fact that it is usually recommended for his patient going through an intratympanic injection should have a driver

Of course he did... That's what doctors are required to tell their patients regardless of the circumstances (ie. clinical trial or not...). When I went for an eye floater examination in Berlin (Germany) last year, the doctors there told me I could not drive afterwards (because of pupil dilation medication). That is what they are required to tell the patient. Now, whether the patient actually listens is another matter (and is not their responsibility...).

Because of that, I opted to only have medication in one eye (against the protocol of the eye clinic). Did I drive afterwards? Who knows...

 

[CathodeRaySound]

@attheedgeofscience

I have just mailed them about further details regarding my case, and that I would like to remain as a candidate for AM-101. All I thought of while I was writing the email was, "why did I NOT get everything on paper or recording" such a shame, because without these documentations the doctor has room to say anything. At this point, I've already accepted the situation, if this doesn't work out I will be moving onto other possible treatments. In the end, there is no forcing him to do anything with AM-101 before my 3 month runs out. Thanks ATEOS for giving suggestions and being supportive.

 

[attheedgeofscience]

Thanks ATEOS for giving suggestions and being supportive.

No problem. Don't give up yet. And keep fighting until all options are exhausted.

"Play nice" to begin with; that way you will often be able to extract information passively (in writing). Send them a summary of the points that were agreed (as you see them). If they don't object, then they have passively agreed to the "allegations". Use that against them...! Once you have the necessary information, then you start to "squeeze". As I say, there is no better feeling in life than getting an asshole to accommodate your demands without having to lift a finger...

Good luck.

 

[earsnothappy]

@CathodeRaySound Is there any other treatment centers that are with in your travel range?

 

[Marius T]

Hi everyone I would like some explanations on my tinnitus. Like I said before it's a noise induced tinnitus who's only 3 weeks old, at first it sounded like an old tv sound in my ears. Then i noticed that when I'm moving my mouse down it's more high-pitched ; also I've noticed that my tinnitus is less intrusive and intense than a week ago. Since yesterday, i've noticed that i'm hearing it in my head instead of my ears but i'm not sure about that. The sound is not loud, I can hear it only in my house or when i'm looking for it.
Do you think it's still going to decrease or that the decrease is only psychological ? I'm also considering taking parts of the AM 101 soon, i'll keep my experience posted on this thread.
Thank you for your time, all the best.

 

[rtwombly]

Hi everyone I would like some explanations on my tinnitus. Like I said before it's a noise induced tinnitus who's only 3 weeks old, at first it sounded like an old tv sound in my ears. Then i noticed that when I'm moving my mouse down it's more high-pitched ; also I've noticed that my tinnitus is less intrusive and intense than a week ago. Since yesterday, i've noticed that i'm hearing it in my head instead of my ears but i'm not sure about that. The sound is not loud, I can hear it only in my house or when i'm looking for it.
Do you think it's still going to decrease or that the decrease is only psychological ? I'm also considering taking parts of the AM 101 soon, i'll keep my experience posted on this thread.
Thank you for your time, all the best.

You are in the phase where it is impossible to say if your tinnitus will persist or resolve, but also the stage where AM-101 can be effective. I would advise you to enroll in the study immediately, as you have nothing to lose and a very small window of opportunity.

New tinnitus moves around in the head, changes tones, cascades into hyperacusis and back again...it's a mad beast. From what I've learned on these forums, I believe this is due to the brain trying to make sense of it as a stimulus and adapting to deal with it. Unfortunately, that adaptation often means the brain continues to perpetuate the tinnitus even after the initial injury has been cleaned up.

By all means sign up for AM-101 before that happens. If you haven't already, go to an ENT for a prescription of prednisone while you wait. It did nothing for me, but can be effective in some cases. Don't wait for the prednisone to work, though. Do AM-101 while you're still a brand new case.

 

[Marius T]

Thank you rtwombly, but here's something new, i've just ride a little motorbike for 15 minutes with earplugs and now I feel like I can hear my tinnitus way louder ! Help me please I can't take it I wish this is only a spike due to the earplugs help !

 

[Marius T]

Do you think it can be psychological ? help please

 

[Rube]

Do you think it can be psychological ? help please

it may only be a spike. try to calm down and relax a bit and try to not concentrate on it and think of something else. if i was you i would try to keep away from loud sounds for a bit.

 

[Marius T]

@Rube actually i'm trying to keep myself away from loud sound but I mean this was only a 15 minutes ride with a little motorbike with earplugs and a helmet which was pretty well covering my ears.. Per say I didn't feel uncomfortable at all and the sound of the bike wasn't bigger than any types of sound i've heard the past 3 weeks.
Thank you for your support and advices !

 

[CathodeRaySound]

@Marius T

From my limited understanding from psych studies and Google, there is a connection between stress and increased glucocorticoid secretion which in turn raises extracelluar glutamate levels, glutamate is considered to be a naturally occurring neurotoxin at concentrated levels, this is what AM-101 (Esketamine) is targeting in the ear, reducing glutamate based cell death and excitation. Drugs like Ketamine and its derivatives are noncompetitive NMDA antagonists, NMDA receptors has to remain open in order for electrical signals to process, and this process requires glutamate to bind with the NMDA receptors creating an activated ion channel. Ketamine inhibits these NMDA receptors through binding to its immediate areas. There are other drugs like Ketamine, but AM-101 (Esketamine) is the first of its kind to be injected locally into the ear, in hopes that it reduces the glutamate action more directly in the ear. Otonomy's OTO-311 uses a similar model, using a completely different drug called gacyclidine, if I understand correctly, it should be less toxic, more potent, and use only one injection since their solution is supposed to dissolve more slowly. I think we are living in a good time right now, many new treatments are coming out. It used to be "deal with it", soon enough our doctors will be offering a vast array of options for us.

Edit: In conclusion, acute and chronic stress might very well be toxic to our ears.

 

[Rube]

@CathodeRaySound if T is believed to occur in the brain, how is am101 effective by being injected into the ear?

 

[CathodeRaySound]

if T is believed to occur in the brain, how is am101 effective by being injected into the ear?

Tinnitus isn't believed to be solely due to the brain, AM-101 is targeting the NMDA receptors in your ear, preventing the overreaction of the immediate byproduct (glutamate) of whatever dysfunction that you may have. The damaging of the cells in your ear due to glutamate might be causing all that noise. On the chance that this might be what you're hearing, I'd hop on it.

Edited to make more sense.

 

[Marius T]

Thank you Cathoderaysound for these pretty good informations, i'm truly sorry that you've been DQ for nothing...

 

[CathodeRaySound]

Thank you Cathoderaysound for these pretty good informations, i'm truly sorry that you've been DQ for nothing...

No problem, and don't be sorry cause unexpected shit happens to anyone under any circumstance. Hope your treatment works out, and make sure you get documentations for everything your study doctor says. He might forget what he said two weeks ago when he himself didn't note everything for himself.

 

[Rube]

Tinnitus isn't believed to be solely due to the brain, AM-101 is targeting the NMDA receptors in your ear, preventing the overreaction of the immediate byproduct (glutamate) of whatever dysfunction that you may have. The damaging of the cells in your ear due to glutamate might be causing all that noise. On the chance that this might be what you're hearing, I'd hop on it.

Edited to make more sense.

thanks man! did you receive a response from the study doctor?

 

[CathodeRaySound]

thanks man! did you receive a response from the study doctor?

Nope, I emailed them Friday, and they're closed on Saturdays and Sundays. I have to wait until Monday for his response.

 

[SteveToHeal]

@Marius T

From my limited understanding from psych studies and Google, there is a connection between stress and increased glucocorticoid secretion which in turn raises extracelluar glutamate levels, glutamate is considered to be a naturally occurring neurotoxin at concentrated levels, this is what AM-101 (Esketamine) is targeting in the ear, reducing glutamate based cell death and excitation. Drugs like Ketamine and its derivatives are noncompetitive NMDA antagonists, NMDA receptors has to remain open in order for electrical signals to process, and this process requires glutamate to bind with the NMDA receptors creating an activated ion channel. Ketamine inhibits these NMDA receptors through binding to its immediate areas. There are other drugs like Ketamine, but AM-101 (Esketamine) is the first of its kind to be injected locally into the ear, in hopes that it reduces the glutamate action more directly in the ear. Otonomy's OTO-311 uses a similar model, using a completely different drug called gacyclidine, if I understand correctly, it should be less toxic, more potent, and use only one injection since their solution is supposed to dissolve more slowly. I think we are living in a good time right now, many new treatments are coming out. It used to be "deal with it", soon enough our doctors will be offering a vast array of options for us.

Edit: In conclusion, acute and chronic stress might very well be toxic to our ears.

Great post and a good explanation for why any current treatment that involves reducing stress can alleviate T. And why most people say exercise helps keep the T monster at bay. Yoga can calm down the whole body/brain system. However, these are time consuming activities and they only act as a sand barrier to T most of the time. Once T has "set in" for the day at say a 9/10, no amount of running that I do, takes it away

Having to be this vigilant over stress is also a real pain. It DQ's me from really getting stuck into anything mentally challenging with high stress levels It's the reason I could no longer to my job. But that is another topic.

I'm looking forward to the days of T being taken care of with a pill. No more need to be so stress / noise avoidant 24/7. Let's hope am101 at least blocks the glutamate, AUT rights the Kv channels and we can get our lives back.

 

[CathodeRaySound]

@SteveToHeal

From what I am studying, neurons are vulnerable to synaptic plasticity, which basically means the ability for synapses of the neurons to strengthen due to repeated stimulation. The longer the pre-synaptic neuron is used to giving off neurotransmitters in our case glutamate to the glutamate receptors (NMDA), the post-synaptic neurons are then reinforced in its ability to become more stronger and more "efficient". This overall process is called LTP or long term potentiation which is the long term augmentation of signal transmission.. So hypothetically speaking, tinnitus is a self reinforcing condition...a positive feedback loop. Now knowing this knowledge, I believe that AM-101 can be beneficial to breaking this loop for short term sufferers, but for people that has chronic tinnitus AUT00063 seems to be very promising if it targets the ion transfer which can reverse the long term potentiation. Hypothetically, if something like AUT00063 is used long enough it might very well "cure" tinnitus, but it also raises the question if the positive feedback loop will be persistent after they stop taking the drug. Perhaps the drug needs to be taken until full neuroplasticity is reached (how would you even determine something like that on a case to case basis?), and the body accepts the new state without tinnitus to be homeostatic...lol the more you know, the more questions it raises. More knowledgeable people please respond with your input with corrections or further details and hypothesis.

 

[Robb]

@SteveToHeal

From what I am studying, neurons are vulnerable to synaptic plasticity, which basically means the ability for synapses of the neurons to strengthen due to repeated stimulation. The longer the pre-synaptic neuron is used to giving off neurotransmitters in our case glutamate to the glutamate receptors (NMDA), the post-synaptic neurons are then reinforced in its ability to become more stronger and more "efficient". This overall process is called LTP or long term potentiation which is the long term augmentation of signal transmission.. So hypothetically speaking, tinnitus is a self reinforcing condition...a positive feedback loop. Now knowing this knowledge, I believe that AM-101 can be beneficial to breaking this loop for short term sufferers, but for people that has chronic tinnitus AUT00063 seems to be very promising if it targets the ion transfer which can reverse the long term potentiation. Hypothetically, if something like AUT00063 is used long enough it might very well "cure" tinnitus, but it also raises the question if the positive feedback loop will be persistent after they stop taking the drug. Perhaps the drug needs to be taken until full neuroplasticity is reached (how would you even determine something like that on a case to case basis?), and the body accepts the new state without tinnitus to be homeostatic...lol the more you know, the more questions it raises. More knowledgeable people please respond with your input with corrections or further details and hypothesis.

AM-101 on a 1 year sufferer, you think has any effect, opinion please?

 

[cdog]

From what I am studying, neurons are vulnerable to synaptic plasticity, which basically means the ability for synapses of the neurons to strengthen due to repeated stimulation. The longer the pre-synaptic neuron is used to giving off neurotransmitters in our case glutamate to the glutamate receptors (NMDA), the post-synaptic neurons are then reinforced in its ability to become more stronger and more "efficient". This overall process is called LTP or long term potentiation which is the long term augmentation of signal transmission.. So hypothetically speaking, tinnitus is a self reinforcing condition...a positive feedback loop.

There are many hypotheses as to the mechanisms that cause and maintain tinnitus. These few pages

http://books.google.com/books?id=YS...triggers of tinnitus related activity&f=false

for example, give a summary of many of them.

LTP is only one of these hypotheses (see page 263 above, section titled "Activity-Dependent Plasticity"). However, even if tinnitus is established through LTP, why is it maintained in the long term? In particular, why don't mechanisms regulating plasticity, such as synaptic scaling kick in and restore some sort of homeostasis?

"If the strength of a synapse is only reinforced by stimulation or weakened by its lack, a positive feedback loop will develop, causing some cells never to fire and some to fire too much. But two regulatory forms of plasticity, called scaling and metaplasticity, also exist to provide negative feedback.[12] Synaptic scaling is a primary mechanism by which a neuron is able to stabilize firing rates up or down.[15]" (http://en.wikipedia.org/wiki/Synaptic_plasticity).​

So hypothetically speaking, tinnitus is a self reinforcing condition...a positive feedback loop. Now knowing this knowledge, I believe that AM-101 can be beneficial to breaking this loop for short term sufferers, but for people that has chronic tinnitus AUT00063 seems to be very promising if it targets the ion transfer which can reverse the long term potentiation.

AUT00063 targets Kv channels, which are part of a different hypothesis of a tinnitus cause - namely, response to defferentation (see page 261 above, section titled "Role Of Deafferentation")

 

[CathodeRaySound]

@Robb

I really couldn't say based on my limited understanding, but my guess is maybe but probably not, because once the LTP sets in for a long duration and a positive feedback loop is created, and the damage is already done; furthermore, at a certain point the brains plasticity will hold onto these changes and create new connections based on the condition, which only reinforces it even further. It is like memory, it is easy to create reinforced memories through stimulation, but extremely hard to "forget" the newly created neural connections without external conditions influencing it. To definitively know anything, we just have to wait for the trial results for chronic tinnitus.

@cdog

I can only guess, but at a certain point a complex connection between the subjective sound due to inner ear neuron dysfunction is created with the brain. LTP and the positive feedback loop only reinforces the "short long term" condition; however, the brain creates maladaptive connections through this on a "chronic long term" basis. I am aware that AUT00063 targets potassium ion channels, but I was thinking the same concept can apply due to the relevance between the NMDA receptors and ion channels at the synaptic junction - one effects the other, while the latter works on the end product, and the former works on the initial stages of neural functions - same system, different target within the system, correct me if I'm wrong. I'm trying to get help in understanding the finer details of tinnitus, I am just beginning to understand the very gist of tinnitus on an in-depth level through studying documents online such as you have provided, and somehow use my pre-existing knowledge from psychology studies from school. This is why I wanted someone like yourself and @benryu to come and make further clarifications and provide further details. It seems like you have come to the same questions I have, which only more seasoned people in neurobiology can provide insight for right now.

 

[CathodeRaySound]

@cdog

I also forgot to comment on the mechanisms which regulates plasticity, do you know if deafferation inhibits the neural functions from doing its job? In this case the regulation of adverse plasticity. After all the death, or disruption of neurons can ruin the ability for them to maintain itself I'd imagine.

 

[Robb]

I had only one injection of AM-101, now one week after I think it did not do anything at all. Even making my T slightly louder.

What can I except? Will my T go down to volume level before, why after one week there is still variance it should have settled down is my opinion..