A Randomized Single-Blind Controlled Trial of a Prototype Digital Polytherapeutic for Tinnitus

[InNeedOfHelp]

University of Auckland scientists are excited by results from a trial of a new treatment for tinnitus.After 20 years searching for a cure for tinnitus, researchers at the University of Auckland are excited by 'encouraging results' from a clinical trial of a mobile-phone-based therapy.

OK, a mobile phone app, there are a dozen already, but wait, look at the results...

The study randomised 61 patients to one of two treatments, the prototype of the new 'digital polytherapeutic' or a popular self-help app producing white noise.

This is more significant than some of our earlier work and is likely to have a direct impact on future treatment of tinnitus," Associate Professor in audiology Grant Searchfield says.

Key to the new treatment is an initial assessment by an audiologist who develops the personalised treatment plan, combining a range of digital tools, based on the individual's experience of tinnitus.

"Earlier trials have found white noise, goal-based counselling, goal-oriented games and other technology-based therapies are effective for some people some of the time," says Dr Searchfield.

"This is quicker and more effective, taking 12 weeks rather than 12 months for more individuals to gain some control."

There is no pill that can cure tinnitus, Dr Searchfield says.

"What this therapy does is essentially rewire the brain in a way that de-emphasises the sound of the tinnitus to a background noise that has no meaning or relevance to the listener."

Audiology research fellow Dr Phil Sanders says the results are exciting and he found running the trial rewarding personally.

"Sixty-five percent of participants reported an improvement. For some people, it was life-changing - where tinnitus was taking over their lives and attention."

Some people didn't notice an improvement and their feedback will inform further personalisation, Dr Sanders says.

Tinnitus is a phantom noise and its causes are complex. It has so far defied successful treatment.

While most people experience tinnitus, or ringing in the ears at least on occasions, around five percent experience it to a distressing degree. Impacts can include trouble sleeping, difficulty carrying out daily tasks and depression.

Dr Searchfield says his work as an audiologist inspired his research, seeing patients' distress and having no effective treatment to offer them. "I wanted to make a difference."

The next step will be to refine the prototype and proceed to larger local and international trials with a view to gaining FDA approval.

The researchers hope the app will be clinically available in around six months.

Breakthrough in Search for Tinnitus Cure

At 12 weeks an TFI reduction of 16 points, placebo controlled. Average TFI before starting was 60. This is not just cognitive behavioral therapy or habituation:

USL had significant effects on ratings of annoyance, ability to ignore and unpleasantness between baseline and 6 weeks of therapy; between baseline and 12 weeks of therapy ratings of annoyance, ability to ignore and unpleasantness remained significant, and the strength of tinnitus (loudness) had also reached threshold for statistical significance. Scales of problem and comfort did not change statistically. The results are consistent with a rapid positive effect that is broadly based.

A randomized single-blind controlled trial of a prototype digital polytherapeutic for tinnitus

 

[DimLeb]

"What this therapy does is essentially rewire the brain in a way that de-emphasises the sound of the tinnitus to a background noise that has no meaning or relevance to the listener."

Sounds an awful lot like TRT with white noise and counselling. I call BS. Next.

 

[Nick47]

I call BS.

 

[2noist]

I also call BS. When you look at the data, the white noise group and treatment group didn't vary much at all, a few measly TFI points (and TFI is a scale of 0 to 100), just enough for them to call their BS treatment clinically significant.

Dr Searchfield, you are fired.

 

[InNeedOfHelp]

I think you have to realize that there will be no one-pill-fix for this problem and that sound therapy to reconfigure the brain shows benefit across several studies. But because it is not the way we want it to be, not in the shape of a pill, we shoot it off instantly for no reason. When there are no treatments available you cannot be picky!

There are no pills to induce brain plasticity. Brain plasticity is all about training the brain.

The difference between the control group and on control group is 10 to 16 points. That is a 66% difference. And reduction of 16 points on an average of 60 points, I would be more then happy with a 25% reduction on TFI scale. Tinnitus loudness reduction reaching point of clinical difference (13 points) to me shows it is not purely habituation.

As you can see 60 TFI is severe Tinnitus. If people with severe Tinnitus state that this is a life changing therapy, i'm interested. And you should be too. Does not matter what the treatment is.

I welcome every treatment which beats the control group and this is one of them. I don't care what type the intervention is. If CBT/TRT would theoretically cause significant reduction of tinnitus loudness, I'd be all in favor of CBT/TRT!

 

[Nick47]

Can't see how this works for hearing loss and hyperacusis. I dunno.

 

[Stayinghopeful]

Honestly, I'd happily take a 10-20% reduction if all it meant is downloading an app and following a listening protocol.

 

[CRGC]

Sounds like a more personalized/"tuned" version of TRT. Might work for some?

 

[Stuart-T]

Individualised treatment plans seem to outscore an impersonal approach so the results are not too surprising.

What they need is a third group - where the individual plans are prescribing the same white noise - just as acupuncture control group places random needles (and finds it works same as expert placement).

If someone believes a treatment plan has been individually tailored to them - chances of placebo effect are high.

 

[hopes]

The story repeats itself.

 

[Toby1972]

Always the same. In the end, study participants give slightly better values, although the whole thing has no effect. Simply a courtesy to the provider, purely a psychological effect. The more complicated the application and the more individually tailored to you, the better values you give. This has happened dozens of times in similar studies.

 

[PeterPan]

TFI reduction of 10.1 for the control and 17.8 for the treatment. No significant statistical TFI reduction difference between the control and treatment arms. Seems like the control was a good one, with the only issue being the staff administering the trial were not blinded.

If it does work, there isn't much effect. I'd say most likely placebo in both arms.

 

[UKBloke]

One positive I take from this is, at least they had the cajones to recruit patients with tinnitus for >6 months and (apparently) no upper limit. A small step in the right direction.

 

[Rb86]

My tinnitus varies over any given day or week like many others. One of my measurements that I've come to learn is if I can hear it while driving down the road. On days where I can say man, it's particularly bothersome, I can hear it over the road noise. On good days I can drive a while and realize it doesn't have my attention and when I listen for it, it's not too obvious. That's a marker for me as it's something I can't tell unless I measure it against the driving noise. The difference being, if I haven't driven, I can't tell if it's louder or not it's just more intrusive one day - truth being it really is louder.

Saying all that to say this - those magic days where it's not as intrusive have a hell of a lot more quality of life to them. If this stupid phone app gives me that or better? I want in.

 

[InNeedOfHelp]

This research has gotten the most traction out of all published research the entire year (since I have started tracking tinnitus research). There are radio interviews and worldwide coverage throughout the last week, including major newspapers. They clearly state there is a reduction in tinnitus loudness and that this is not just a coping strategy. You guys are dismissing this too soon.

Digital Therapy May 'Rewire' the Brain to Improve Tinnitus

 

[DimLeb]

This research has gotten the most traction out of all published research the entire year (since I have started tracking tinnitus research). There are radio interviews and worldwide coverage throughout the last week, including major newspapers. They clearly state there is a reduction in tinnitus loudness and that this is not just a coping strategy. You guys are dismissing this too soon.

For anyone not having tinnitus, yeah, it seems it would work and it would be a treatment. But no. These 3 things in the same sentence: "white noise, active game-based therapy and counseling" are what TRT mostly is. Neither of those attacks tinnitus at its roots, so any improvement would just be a placebo reaction. Anything that has "counseling" inside is going to be a waste of time.

 

[InNeedOfHelp]

For anyone not having tinnitus, yeah, it seems it would work and it would be a treatment. But no. These 3 things in the same sentence: "white noise, active game-based therapy and counseling" are what TRT mostly is. Neither of those attacks tinnitus at its roots, so any improvement would just be a placebo reaction. Anything that has "counseling" inside is going to be a waste of time.

Funny how this community is desperate but this community does not want to be helped.

It just complains on how bad things are and burns down many attempts to help then.

You all think that the only thing that can help is pharmaceutical intervention. It has been studied numerous times that tinnitus can improve over time. For some it even fades. In the first months, if you stop focussing on the sound, you have a greater chance of recovery. If you actively seek or listen the sound, there is a bigger change it gets stuck in the brain. Because you are training your brain to listen and focus on the sound. It is called neuroplasticity.

Neuroplasticity can be reversed the other way around. Residual inhibition for example. Listening to specific frequencies can reduce the tinnitus loudness significantly for a short time.

The same as VR interventions for tinnitus that are being developed. It is not cognitive. It is actual brain training that attempts to weaken the tinnitus signal.

If this treatment can induce residual inhibition by sound therapy in combination with counseling, and this lowers your TFI, THI and even your actual tinnitus loudness, whereas on the other end you have no intervention and become depressed and suicidal, my choice would be very obvious.

Anyways, no point of discussing this more.

 

[DimLeb]

neuroplasticity

Neuroplasticity is so vague as a brain biology that it's almost useless to count on it with something so specific as tinnitus. It's different for everyone and we don't know (or can prove) if it really happens or if it doesn't. If that was the case, then continueing with life and exposing yourself to sounds would make tinnitus less and less long term. But if you ask tinnitus veterans (10, 20 or more years of tinnitus), they will usually tell you that they have just got used to it, but the noise hasn't changed (or even got worse).

This is coming from me, a musician that makes sounds everyday all day (in always reasonable volume) that cover it during the day and rain/nature sounds during sleep (no headphones). I also regularly try to induce residual inhibition to my 3-4 tinnitus sounds, but to no avail. Even though I have it mild - heard in quiet rooms mostly, I would have noticed any improvements by now, but nope. It has even gotten worse, little by little since onset 1 and a half years ago.

Sorry if I come across as a bit harsh, but my logic says that it's not some pep talk that will bring the change to some "customized" sound therapy. Many people here have already figured out sound therapies that help them cope, anyway.

If we keep insisting that this kind of tinnitus therapy REALLY helps us, then this is what we will keep getting from the medical community.

 

[DaveFromChicago]

Listening to specific frequencies can reduce the tinnitus loudness significantly for a short time.

Did you get this Julian Cowan Hill?

I don't care if this is scientifically demonstrable (and my ENT Doctor maintains that it is not); in spite of many sincere efforts regarding these methods, I have never received any appreciable improvement.

My tinnitus has not improved over longer than an 8.5 year period. In fact, the spikes are very noticeably worse.

I have trained myself not to focus on the sound, and this has not made the slightest difference whatsoever in the nature or character of my tinnitus. It is impervious to every sustained effort towards "neuroplasticity" that I have made.

 

[chinup]

This is not just cognitive behavioral therapy or habituation

 

[GeorgeLG]

Did you get this Julian Cowan Hill?

I don't care if this is scientifically demonstrable (and my ENT Doctor maintains that it is not); in spite of many sincere efforts regarding these methods, I have never received any appreciable improvement.

My tinnitus has not improved over longer than an 8.5 year period. In fact, the spikes are very noticeably worse.

I have trained myself not to focus on the sound, and this has not made the slightest difference whatsoever in the nature or character of my tinnitus. It is impervious to every sustained effort towards "neuroplasticity" that I have made.

@DaveFromChicago, does it affect your life more, less or the same since training yourself to not focus on the sound?

George

 

[tpj]

When you have screaming, screeching, piercing tinnitus, the whole concept of focus is bizarre.

 

[DaveFromChicago]

@DaveFromChicago, does it affect your life more, less or the same since training yourself to not focus on the sound?

Right now we have a rainy front with a barometric pressure change that, as I write this, has spiked my tinnitus so loudly that I was afraid of blacking out and losing total control of the car.

That is my primary difficulty with habituation; to protect itself against this onslaught of invasive pain, my mind seems to be saying, "Let's close up shop", and I have to make a mammoth effort not to pass out not matter what coping reassurances I summon.

What the habituationists fail to consider is that this is an integral protective mechanism employed by the brain; Jacobo Timerman, for example, wrote that when he was tortured during the Argentine Dirty War he would frequently lose consciousness. It is the mind's way of "escaping" from an intolerable situation.

To answer your question, these spikes have lately been kamikazes that have imploded my capacity not to focus on the sound.

In AA, there was the mordant, frequently cited comment that the longer you went without a drink, the closer you got to your next one. The longer I go without a spike, the more pitilessly cruel the next one will be.

This is an utterly insufferable way to live. A woman I know has a small cancerous growth in her intestine, but she is not consumed with anxiety because it is treatable; there is a plan and an anticipated, probably successful end to this. The real despair about this is that there is literally nothing I can do alter or reduce these spikes, or have a medical plan for their diminution.

 

[GeorgeLG]

Right now we have a rainy front with a barometric pressure change that, as I write this, has spiked my tinnitus so loudly that I was afraid of blacking out and losing total control of the car.

That is my primary difficulty with habituation; to protect itself against this onslaught of invasive pain, my mind seems to be saying, "Let's close up shop", and I have to make a mammoth effort not to pass out not matter what coping reassurances I summon.

What the habituationists fail to consider is that this is an integral protective mechanism employed by the brain; Jacobo Timerman, for example, wrote that when he was tortured during the Argentine Dirty War he would frequently lose consciousness. It is the mind's way of "escaping" from an intolerable situation.

To answer your question, these spikes have lately been kamikazes that have imploded my capacity not to focus on the sound.

In AA, there was the mordant, frequently cited comment that the longer you went without a drink, the closer you got to your next one. The longer I go without a spike, the more pitilessly cruel the next one will be.

This is an utterly insufferable way to live. A woman I know has a small cancerous growth in her intestine, but she is not consumed with anxiety because it is treatable; there is a plan and an anticipated, probably successful end to this. The real despair about this is that there is literally nothing I can do alter or reduce these spikes, or have a medical plan for their diminution.

@DaveFromChicago, I know from your posts that you have a tortuous case of tinnitus and you suffer tremendously, I get that and I am sorry for your pain. I also know that you are frustrated that there is no cure, that's understandable. I understand your suffering brother. My pain hyperacusis has been raging this week making me virtually shut in with earplugs and earmuffs cowering in an interior bathroom with a Florida thunderstorm raging over my house. My cancer is stage 4 and incurable. A lengthy discussion with my cancer doctor last week was unpleasant and chemo sucked. I lost my wife to cancer and now live and suffer alone. We will both likely never be cured and never see what a "normal" day used to look like. Life can be very difficult sometimes.

I am particularly interested in the answer to my question from you because you are suffering so much and are so frustrated. I am trying to understand if any improvement short of complete cure has any value to someone in your situation. Or if it's a matter of being too far above the insanity threshold for anything short of say 80% improvement having any benefit. I personally constantly look for any improvement possible and will accumulate whatever I get but it appears that everyone may not see it as I do. BTW, I don't know what habituation means to everyone, I just look for improvement.

George

 

[InNeedOfHelp]

@DaveFromChicago, I know from your posts that you have a tortuous case of tinnitus and you suffer tremendously, I get that and I am sorry for your pain. I also know that you are frustrated that there is no cure, that's understandable. I understand your suffering brother. My pain hyperacusis has been raging this week making me virtually shut in with earplugs and earmuffs cowering in an interior bathroom with a Florida thunderstorm raging over my house. My cancer is stage 4 and incurable. A lengthy discussion with my cancer doctor last week was unpleasant and chemo sucked. I lost my wife to cancer and now live and suffer alone. We will both likely never be cured and never see what a "normal" day used to look like. Life can be very difficult sometimes.

I am particularly interested in the answer to my question from you because you are suffering so much and are so frustrated. I am trying to understand if any improvement short of complete cure has any value to someone in your situation. Or if it's a matter of being too far above the insanity threshold for anything short of say 80% improvement having any benefit. I personally constantly look for any improvement possible and will accumulate whatever I get but it appears that everyone may not see it as I do. BTW, I don't know what habituation means to everyone, I just look for improvement.

George

I feel for you. My tinnitus is bad as well and I'd make the cancer resemblance, like @DaveFromChicago did too. My wife got cancer two months into tinnitus. We had a horrible time during chemo - she was very sick, lost her hair, eyelashes and could barely get out of bed the days after the treatment. She made it through and is better now (but with tinnitus from the platinum chemotherapy and many other permanent body changes - and the fear of cancer coming because it was very aggressive).

It made me put things in perspective and I try not to compare with any other disease. You don't want cancer. It brings its own problems. Diseases like MS, ALS may slowly take you from the inside, where you may not be even able to go to the bathroom alone and makes you fully dependent from someone. You don't want that either.

I am suffering tremendously. I bought a house in a to be developed environment before tinnitus, and it got delivered when t got tinnitus. I have gotten blasted by saws, drills, trucks so often that I lost count. I am having sound based spikes that last a week and I go from one spike to the next- my longest period without tinnitus spike was 6 days. I'm worsening and have no chance to escape, and even though I am in a torturous spike again as we speak, I try to hold on and be positive.

Knowing that this is finite and at some point we will get our lives partially back, helps. I have read a ton of research. We are very close to relief and should cherish all the opportunities that can help us.

 

[GeorgeLG]

I feel for you. My tinnitus is bad as well and I'd make the cancer resemblance, like @DaveFromChicago did too. My wife got cancer two months into tinnitus. We had a horrible time during chemo - she was very sick, lost her hair, eyelashes and could barely get out of bed the days after the treatment. She made it through and is better now (but with tinnitus from the platinum chemotherapy and many other permanent body changes - and the fear of cancer coming because it was very aggressive).

It made me put things in perspective and I try not to compare with any other disease. You don't want cancer. It brings its own problems. Diseases like MS, ALS may slowly take you from the inside, where you may not be even able to go to the bathroom alone and makes you fully dependent from someone. You don't want that either.

I am suffering tremendously. I bought a house in a to be developed environment before tinnitus, and it got delivered when t got tinnitus. I have gotten blasted by saws, drills, trucks so often that I lost count. I am having sound based spikes that last a week and I go from one spike to the next- my longest period without tinnitus spike was 6 days. I'm worsening and have no chance to escape, and even though I am in a torturous spike again as we speak, I try to hold on and be positive.

Knowing that this is finite and at some point we will get our lives partially back, helps. I have read a ton of research. We are very close to relief and should cherish all the opportunities that can help us.

@InNeedOfHelp, sorry for your suffering for you and your wife. My wife and I had cancer at the same time, 6 in total. Cancer is its own beast and can be its own tough challenge but there is progress in that area every day. I hope your wife has success with her treatments and that better days are ahead for you both. Try to get the best out of every day and cherish every single day together. Life can be beautiful buts it's also fragile.

George

 

[Hazel]

I'm afraid it's not a good study. The results are basically the same as for most other trials so far, regardless of which treatment is being tested: Success is claimed based on some marginal improvement as measured through a self-assessment survey (THI, TFI, etc.) with a random threshold for 'clinical significance'.

A 13-point reduction in TFI (the 'clinical significance' threshold) essentially means being somewhat less bothered. This result can and has been achieved many times by any kind of intervention; it's a combination of placebo, natural improvement, and patients responding to getting a lot of personal attention from clinicians. Who knows how these patients will be doing a year or so later; that almost never gets measured.

It also matters what you compare your treatment against. They chose white noise, which in my view is one of the poorest forms of sound therapy (compared to for instance amplitude modulation or notched music), so not exactly a fair comparison. Even so, the paper shows that the TFI decreases for both treatment and control almost at the same rate, and the slight difference between treatment outcomes is not statistically significant. So essentially, the authors themselves are stating that their treatment is just as good/bad as white noise.

A proper control group, one that gets no intervention whatsoever, would have helped strengthen the statistics (but perhaps not in favour of the study). And of course, TFI is a poor outcome measure compared to minimum masking level or similar.

That said, it is at least an RCT-like study, with reasonable sample size; I've definitely seen much poorer study design in tinnitus. And at least they didn't select any patients who've had tinnitus for less than six months. But when it comes to outcomes, this is really is nothing we haven't seen before, and quite astounding to see it being marketed as a "breakthrough" and "cure" by ScienceDaily.

I do appreciate OP for trying to see a silver lining, and I'm not saying tinnitus research is all bad. But it's important that we, as a community, are critical of study design and especially of how study results are communicated. Reading the ScienceDaily article versus the actual paper it's hard to believe they're talking about the same study!

 

[AnthonyMcDonald]

I think you have to realize that there will be no one-pill-fix for this problem

Xenon Pharmaceuticals' XEN1101 — Kv7 Potassium Channel Modulator

 

[GeorgeLG]

I'm afraid it's not a good study. The results are basically the same as for most other trials so far, regardless of which treatment is being tested: Success is claimed based on some marginal improvement as measured through a self-assessment survey (THI, TFI, etc.) with a random threshold for 'clinical significance'.

A 13-point reduction in TFI (the 'clinical significance' threshold) essentially means being somewhat less bothered. This result can and has been achieved many times by any kind of intervention; it's a combination of placebo, natural improvement, and patients responding to getting a lot of personal attention from clinicians. Who knows how these patients will be doing a year or so later; that almost never gets measured.

It also matters what you compare your treatment against. They chose white noise, which in my view is one of the poorest forms of sound therapy (compared to for instance amplitude modulation or notched music), so not exactly a fair comparison. Even so, the paper shows that the TFI decreases for both treatment and control almost at the same rate, and the slight difference between treatment outcomes is not statistically significant. So essentially, the authors themselves are stating that their treatment is just as good/bad as white noise.

A proper control group, one that gets no intervention whatsoever, would have helped strengthen the statistics (but perhaps not in favour of the study). And of course, TFI is a poor outcome measure compared to minimum masking level or similar.

That said, it is at least an RCT-like study, with reasonable sample size; I've definitely seen much poorer study design in tinnitus. And at least they didn't select any patients who've had tinnitus for less than six months. But when it comes to outcomes, this is really is nothing we haven't seen before, and quite astounding to see it being marketed as a "breakthrough" and "cure" by ScienceDaily.

I do appreciate OP for trying to see a silver lining, and I'm not saying tinnitus research is all bad. But it's important that we, as a community, are critical of study design and especially of how study results are communicated. Reading the ScienceDaily article versus the actual paper it's hard to believe they're talking about the same study!

@Hazel, excellent balanced perspective and good information.

George

 

[GeorgeLG]

Xenon Pharmaceuticals' XEN1101 — Kv7 Potassium Channel Modulator

@AnthonyMcDonald, that's a long thread, what's the takeaway?

George