Otonomy OTO-313 — Treatment of Tinnitus

[Pharz]

No concern here. If there were some severe adverse reactions with the extended release gel, it would affect both placebo and drug participants. So, the gel itself would be of safety concern, but it isn't.

I am always wondered about one thing: If the hair cells are so delicate and the cochlea can so easily be damaged, how can it actually tolerate a liquid that is being injected to it? It's kind of worrying...

I got Dexamethasone shots in my ear personally but that was simply watery and came out when I tilted my head sideways, but a gel sounds a bit strange.

 

[star-affinity]

I am always wondered about one thing: If the hair cells are so delicate and the cochlea can so easily be damaged, how can it actually tolerate a liquid that is being injected to it? It's kind of worrying...

That's a good question I think. I've also been thinking about vibrations and standing on the head and doing other physical activities with the body. Boxing? How can the cells and synapses in the cochlea tolerate that?

But I guess the largest "impact" to the cells and synapses in the head comes from sound that goes via the ear drum when it vibrates and makes the liquid in the cochlea move. But this is just my guess – I'm not educated in the matter.

I'm also curious as to how the drugs are administered in to the cochlea. Is it done the same way? Are all going through the Round Window? How can a liquid or gel enter the cochlea via the Round Window without the liquid in the cochlea coming out? The Round Window has permeability? Many questions.

 

[Aleksandar]

I'm also curious as to how the drugs are administered in to the cochlea. Is it done the same way? Are all going through the Round Window? How can a liquid or gel enter the cochlea via the Round Window without the liquid in the cochlea coming out? The Round Window has permeability? Many questions.

How can a liquid or gel enter the cochlea via the Round Window without the liquid in the cochlea coming out? Best question

 

[UHPTS]

How can a liquid or gel enter the cochlea via the Round Window without the liquid in the cochlea coming out? Best question

The same way as when you put cream on your skin to treat pain and it enters your body while your blood stays in. Or when you are a Russian spy who wants to kill an ex Russian spy in Salisbury, you just put your stuff on the door handle and somehow it finds its way to the victim's body. And as you could see even small amount was super effective...

 

[patorjk]

I was going through the original paper on Gacyclidine and tinnitus and noticed of the 6 patients treated, 1 had a complete recovery (patient #5):

The other 3 responders relapsed after a period of time. Patient #5 had only had tinnitus for a month, so it's possible they recovered on their own, but it'd be interesting to know if anyone from the Phase 1/2 study had a complete recovery.

 

[star-affinity]

How can a liquid or gel enter the cochlea via the Round Window without the liquid in the cochlea coming out? Best question

The same way as when you put cream on your skin to treat pain and it enters your body while your blood stays in. Or when you are a Russian spy who wants to kill an ex Russian spy in Salisbury, you just put your stuff on the door handle and somehow it finds its way to the victim's body. And as you could see even small amount was super effective...

So it seems we're talking about permeability when it comes to the Round Window then? Somewhat similar to the skin?

At the same time it sounds like it it must be difficult to know if the gel containing the drug reaches the intended places in the cochlea if the results of the application can't be verified. Or can they?

I mean, it's not strange that a drug that hasn't been administered correctly won't work.

 

[UHPTS]

At the same time it sounds like it it must be difficult to know if the gel containing the drug reaches the intended places in the cochlea if the results of the application can't be verified. Or can they?

If I recall, correctly, Frequency Therapeutics cooperated with a hearing clinic in Hanover to verify that the treatment molecules reach the liquid in cochlea. The validation was successful. OTO-313 should be the same.

 

[Sentinel]

I get my first injection tomorrow morning and I'm leaving tonight to drive up to a hotel near the trial site so I don't have to face morning Charlotte traffic. Having a super low tinnitus day today which is weird but welcome. I'll keep y'all updated if anything miraculous or terrible happens. Also looking forward to hearing from some of the other people doing the trial.

Glad to finally be taking this next step on my tinnitus journey.

 

[Exit]

I get my first injection tomorrow morning and I'm leaving tonight to drive up to a hotel near the trial site so I don't have to face morning Charlotte traffic. Having a super low tinnitus day today which is weird but welcome. I'll keep ya'll updated if anything miraculous or terrible happens. Also looking forward to hearing from some of the other people doing the trial.

Glad to finally be taking this next step on my tinnitus journey.

Wish you good luck and an incredible miraculous recovery!

Have a good night.

 

[Pharz]

I get my first injection tomorrow morning and I'm leaving tonight to drive up to a hotel near the trial site so I don't have to face morning Charlotte traffic. Having a super low tinnitus day today which is weird but welcome. I'll keep y'all updated if anything miraculous or terrible happens. Also looking forward to hearing from some of the other people doing the trial.

Glad to finally be taking this next step on my tinnitus journey.

I wish you all the best and hope for some awesome updates!

 

[TrevorSanders]

I get my first injection tomorrow morning and I'm leaving tonight to drive up to a hotel near the trial site so I don't have to face morning Charlotte traffic. Having a super low tinnitus day today which is weird but welcome. I'll keep ya'll updated if anything miraculous or terrible happens. Also looking forward to hearing from some of the other people doing the trial.

Glad to finally be taking this next step on my tinnitus journey.

I'll let you know how it goes for me. The place I'm supposed to go to is super unresponsive and I've had to call a dozen times to even set up a date for the appointment. In my opinion, it's super irresponsible how lackadaisical they're taking this study.

 

[Gee82]

@TrevorSanders, @Sentinel, best of luck to both of you. I wish you silence. Please keep us posted.

 

[star-affinity]

In my opinion, it's super irresponsible how lackadaisical they're taking this study.

It makes me sad and frustrated when topics that seriously affect people's lives aren't taken seriously or handled in a thorough and caring way.

Hope all goes well!

 

[Gee82]

I get my first injection tomorrow morning

How many injections are you going to get? I thought you were supposed to get only one based on the trial design.

 

[AfroSnowman]

@TrevorSanders and @Sentinel, thanks for doing this. You aren't just doing this for yourselves but you are doing this for all of us.

Good luck.

 

[TrevorSanders]

Update: First appointment is tomorrow (July 8th). They said the injection will be delivered 2 weeks after the first appointment, so on July 22nd. I will continue to give updates as things progress.

 

[twa]

@Sentinel, @TrevorSanders, I'm praying all will go smoothly with great results! You have all of us behind you right now! XO

 

[canteven]

I'm looking forward to seeing what your results are as well.

 

[aorelia]

I get my first injection tomorrow morning and I'm leaving tonight to drive up to a hotel near the trial site so I don't have to face morning Charlotte traffic. Having a super low tinnitus day today which is weird but welcome. I'll keep y'all updated if anything miraculous or terrible happens. Also looking forward to hearing from some of the other people doing the trial.

Glad to finally be taking this next step on my tinnitus journey.

I'm thinking about contacting the site near me.

How has your experience been so far?

 

[Sentinel]

How many injections are you going to get? I thought you were supposed to get only one based on the trial design.

Yes, I'm sorry I misspoke, it's only one injection.

@TrevorSanders and @Sentinel, thanks for doing this. You aren't just doing this for yourselves but you are doing this for all of us.

Good luck.

Thank you Snowman, that means the world to me as I'm going through a lot at the moment. Even if I get the placebo I still wanted to try and give folks some hope. Thankfully we've got me and @TrevorSanders doing the trial so we will have some data before the results are officially released next year.

@Sentinel, @TrevorSanders, I'm praying all will go smoothly with great results! You have all of us behind you right now! XO

Thank you @twa your posts on this forum are always great to read and you're certainly a welcome source of positivity in my more negative moments.

I'm thinking about contacting the site near me.

How has your experience been so far?

I've had a great experience with the clinic I have worked with. I've been compensated $25 for all my diary entries between visits and $50 per visit, in addition to having all my gas and hotel costs covered. The staff at the clinic have been great to work with and the physician there is a really nice guy and is the sort of Doctor very much looking to give his patients a solution to problems like tinnitus as opposed to just telling them to put on a fan and deal with it.

The actual visit was fairly straightforward, they numbed me 15 minutes prior to the injection and I didn't feel anything during the injection but I heard some weird sounds. After 45 minutes I left and headed out to lunch before going home. I got quite a bad headache which repeated today and have experienced a lot of crackling in the ear that received the injection when yawning or moving my jaw. I don't think the headaches have anything to do with it. My hearing has been affected in some sort of way but the effect seems to be going away.

My tinnitus has also increased since the injection but not beyond its normal range. It was very low prior to the injection and was worse the night after and all of today. It's nothing to be worried about though and shouldn't preclude anyone who wants to go for the trial to try it.

I'm going through a pretty rough patch with it at the moment with depression at having been going through this for 7 months but I'm basically just waiting at this point to see if any changes occur. I've got 3 more visits to the clinic to update them on my status and answer more questionnaires that will make up my Tinnitus Functional Index info that will be sent to Otonomy. I'd love to answer anymore questions anybody has and I'll post updates here as they occur. If I wake up several mornings in a row with my tinnitus inexplicably reduced you guys will be the first to hear aside from my family as they have had to put up with supporting me through all this.

Thanks for all the posts and support, it means the world to me.

 

[Sentinel]

I'll let you know how it goes for me. The place I'm supposed to go to is super unresponsive and I've had to call a dozen times to even set up a date for the appointment. In my opinion, it's super irresponsible how lackadaisical they're taking this study.

I'm very sorry you've had to go through that, the clinic I have been working with has been very helpful through the entire process. I hope that things improve once you advance a little further. It would be nice to have you and me both as forum members in the study to provide feedback on the forum here so we don't have to wait until the results release next year.

 

[Sentinel]

Positive update:

Tinnitus is a barely audible hiss today, it altered tone this morning to something that seemed much higher of a frequency and then went to a hiss. Hopefully, it continues. I think my ear has normalized somewhat from the injection it doesn't feel like I have swimmer's ear anymore.

I'll take it.

 

[aorelia]

Positive update:

Tinnitus is a barely audible hiss today, it altered tone this morning to something that seemed much higher of a frequency and then went to a hiss. Hopefully, it continues. I think my ear has normalized somewhat from the injection it doesn't feel like I have swimmer's ear anymore.

I'll take it.

Appreciate the updates! I wonder if transitioning from a higher frequency to a hiss is part of a healing mechanism.

 

[GCS]

Positive update:

Tinnitus is a barely audible hiss today, it altered tone this morning to something that seemed much higher of a frequency and then went to a hiss. Hopefully, it continues. I think my ear has normalized somewhat from the injection it doesn't feel like I have swimmer's ear anymore.

I'll take it.

Great to hear, is it even lower than before treatment?

 

[Exit]

Positive update:

Tinnitus is a barely audible hiss today, it altered tone this morning to something that seemed much higher of a frequency and then went to a hiss. Hopefully, it continues. I think my ear has normalized somewhat from the injection it doesn't feel like I have swimmer's ear anymore.

I'll take it.

Congrats!

Curious, have you had this low tinnitus any time before in the past 7 months...?

Be very careful with loud incidents over the next weeks.

 

[Sentinel]

Congrats!

Curious, have you had this low tinnitus any time before in the past 7 months...?

Be very careful with loud incidents over the next weeks.

This is at the absolute lowest of a normal fluctuation of my tinnitus. It's been this low before but it remains to be seen if it'll stay this way.

Great to hear, is it even lower than before treatment?

It's at the lower end of the spectrum of where it normally varies.

Seems that most people that got the drug took weeks to improve so this may just be a normal fluctuation, it's still early days. However, I will also say that I took Klonopin before the trial and it lowered it to about this level so that's good news.

Also, not to be a downer BUT: Otonomy has this theory about the peripheral auditory system and the release of Glutamate damaging synapses and generating tinnitus in the first six months after an insult. @Contrast made posts on this in the first few pages of this thread and how he thought that it was silly to treat tinnitus in this manner because eventually, the cause of the tinnitus is caused by the lack of input from either synapses or hair cells at some level. Now I tend to agree with him in this regard, and Otonomy made the choice to open the trial up to people like me who sit at the 6 months - 1 year mark to see if there was any improvement. I don't know if this is the best choice however we simply don't have data for people like me that sit in this area.

We will simply have to wait and see.

 

[Toby1972]

Positive update:

Tinnitus is a barely audible hiss today, it altered tone this morning to something that seemed much higher of a frequency and then went to a hiss. Hopefully, it continues. I think my ear has normalized somewhat from the injection it doesn't feel like I have swimmer's ear anymore.

I'll take it.

That sounds good, but unfortunately you posted before the injection that your tinnitus was minimal, now we will probably not know whether the changes have to do with your daily changes or with OTO-313.

I need a candidate with constant 8/10 to 9/10 tinnitus to report to us.

 

[Damocles]

Appreciate the updates! I wonder if transitioning from a higher frequency to a hiss is part of a healing mechanism.

It definitely is.

My further damaged ear (the one that developed tinnitus as a result of NIHL+Ear Infection) has louder, lower frequency multi-tonal noises; whereas my lesser damaged ear (the one that developed tinnitus as a result of NIHL alone) has maintained a comparatively pleasant hiss for the past 20 years.

This is a conclusion completely based off of my own experience of course, but I'm pretty sure there are users who will back this up. I'm confident there is a correlation.

 

[Brian Newman]

I wonder if transitioning from a higher frequency to a hiss is part of a healing mechanism.

It is 100%.

 

[star-affinity]

This is at the absolute lowest of a normal fluctuation of my tinnitus. It's been this low before but it remains to be seen if it'll stay this way.

It's at the lower end of the spectrum of where it normally varies.

Seems that most people that got the drug took weeks to improve so this may just be a normal fluctuation, it's still early days. However, I will also say that I took Klonopin before the trial and it lowered it to about this level so that's good news.

Also, not to be a downer BUT: Otonomy has this theory about the peripheral auditory system and the release of Glutamate damaging synapses and generating tinnitus in the first six months after an insult. @Contrast made posts on this in the first few pages of this thread and how he thought that it was silly to treat tinnitus in this manner because eventually, the cause of the tinnitus is caused by the lack of input from either synapses or hair cells at some level. Now I tend to agree with him in this regard, and Otonomy made the choice to open the trial up to people like me who sit at the 6 months - 1 year mark to see if there was any improvement. I don't know if this is the best choice however we simply don't have data for people like me that sit in this area.

We will simply have to wait and see.

Thanks for updating us and hope the tinnitus keeps getting lower!

I read that post from @Contrast on the first page of this thread and it really got me thinking about the difference between tinnitus being central vs peripheral. @Contrast subscribes to a model that tinnitus is always central and never peripheral. Now, correct me if I'm wrong but if I understand correctly central = the brain and peripheral = the inner ear. Or?

If this is the case, this would mean we cannot treat tinnitus by "fixing" things in the inner ear (cochlea) since by the "tinnitus is central" argument it's not anything in the cochlea that's causing the tinnitus – even if an acoustic trauma and hearing-loss was involved when the tinnitus was triggered. Or am I understanding this theory incorrectly?

If this is the case, what is it about OTO-313 that makes it possible to treat tinnitus within six months from onset and why is it less likely to work after that period of time? What is it that happens after that six month time frame?

It seems tinnitus can be triggered from both acoustic trauma and stress related factors, just like I got a new tinnitus (hum/drone) while sleeping after having had a bunch of beers one night in December last year. This was definitely not related to an acoustic trauma.

I was thinking if the source of the tinnitus can be coming from both, i.e. in some cases be more neurological (synapses in the audio cortex having trouble?) and in other cases be related to the inner ear like when an acoustic trauma has occurred.

But if one has got tinnitus from an acoustic trauma and has hearing loss in those frequencies that an audiogram shows, wouldn't it be likely that treating the possibly damaged synapses and outer hair cells would get rid of the tinnitus, or are there reasons to believe that is not the case? If the inner ear isn't involved in generating the tinnitus after the onset has occurred (or after a certain time after onset), I don't understand why we hope that applying drugs to the inner ear will ever help when it comes to tinnitus. But maybe we simply don't know currently?

Sorry if this has been covered before.