Lenire — Bimodal Stimulation Treatment by Neuromod

Extremely well stated, MadsWithT.

I underwent exactly the same process experienced by many others of ardent hope reduced to barely sufferable disappointment with Desyncra.

The real lack of utility of Lenire is clearly demonstrated by the news that they have been unable to obtain FDA approval in the US.

This has also compelled my skepticism regarding Dr. Shore's device.

I still maintain that a drug will be the real treatment answer.

And you're quite correct; this condition has yielded many True Believers who have confused Placebo Chimera (defined as "a thing that is hoped or wished for but is in fact illusory or impossible to achieve") with evident, measurable results.

 

How I think of Lenire is this: It's an experimental therapy in the early stages.

If you have hyperacusis with no hearing loss, there's a good chance you'll get benefit.

If you have neither hearing loss nor hyperacusis, maybe you'll get some result.

If you have hearing loss with no hyperacusis, not worth the price tag.

It's still not understood why this is and Neuromod does not know either.

The Tinnitus Talk User Experience Group results were in line with the TENT-A1 study.

That's all that is known to base a decision to try Lenire on.

However, with the pharmaceutical drugs in development, if you can wait, or wait until more is known about neuromodulation, then hold back.

Personally I can wait.

 

A neurosurgeon I used to work with just posted this. Doesn’t seem to contain anything we don’t already know, but it’s in the media. Interesting bit in there about the differences between Lenire and Shore’s approach. Last paragraph talks about next steps being brain imaging to see what’s really changing in the brain.

New Tinnitus Treatment Alleviates Annoying Ringing in the Ears

 

Good Morning,

I am getting in touch about some very positive news from Neuromod. The Company have just published the results of its large scale clinical trial, concluding it’s non-invasive stimulation device known as Lenire® can significantly reduce tinnitus symptoms.

Tinnitus, commonly known as “ringing in the ears” is a condition that affects 10-15% of the population worldwide. Currently there is no cure for this condition, and Lenire®, a device that delivers sound to the ears and electrical stimulation to the tongue, is the first of its kind to clinically demonstrate long-term improvement in patients.

Conducted at the Wellcome Trust-HRB Clinical Research Facility, St. James’s Hospital, Dublin, Ireland and the Tinnituszentrum of the University Regensburg, Germany, the study represents the largest and longest followed-up clinical trial ever conducted in the tinnitus field and it’s a breakthrough for tinnitus research and treatment.

Full press release attached and below and I have also included an infographic with summary detail. We have Dr. Ross O’Neil, the company’s CEO and Dr.Brendan Conlon CMO, available to discuss the topics involving Tinnitus and the positive trial results, and if you need any other information, let us know,

Many thanks,

Aline

Neuromod Publishes Results of Large-Scale Tinnitus Clinical Trial in Peer-Reviewed Top-Tier Scientific Journal

• Clinical trial concludes that bimodal neuromodulation combining sound and electrical stimulation of the tongue can significantly reduce tinnitus symptoms, and therapeutic effects can be sustained for up to 12 months post-treatment.

• 77.8% of participants said they would recommend the Company’s Lenire® device to others with tinnitus.

• 80.1% of treatment compliant participants experienced continued improvement in tinnitus symptom severity when evaluated 12-months post-treatment.

DUBLIN, Ireland | 8 October 2020 – Neuromod Devices Limited (“Neuromod”), the Irish medical device company specialising in the treatment of chronic tinnitus, commonly described as ‘ringing in the ears’, has published the results of the Company’s TENT A1 (Treatment Evaluation of Neuromodulation for Tinnitus) clinical trial in this week’s edition of Science Translational Medicine in a paper titled: ‘Bimodal neuromodulation combining sound and tongue stimulation reduces tinnitus symptoms in a large randomized clinical study’.

The clinical trial was conducted between 2016 and 2019 and was designed to track changes in tinnitus symptom severity. The trial investigated the bimodal neuromodulation approach, using Neuromod’s non-invasive stimulation device that delivers sound to the ears and electrical stimulation to the tongue.

The study represents the largest and longest followed-up clinical trial ever conducted in the tinnitus field with 326 enrolled participants, providing evidence regarding the safety, efficacy and patient tolerability of bimodal neuromodulation for the treatment of tinnitus. 86.2% of treatment compliant participants reported an improvement in tinnitus symptom severity when evaluated after 12 weeks of treatment, with many experiencing sustained benefit 12 months post-treatment.

The study was conducted at the Wellcome Trust-HRB Clinical Research Facility, St. James’s Hospital, Dublin, Ireland and the Tinnituszentrum of the University Regensburg, Germany. There were consistent therapeutic outcomes across both clinical sites, with no SAEs Serious Adverse Events (SAEs related to the treatment and a high satisfaction rate across a large cohort of participants. A Medical Research Organization (NAMSA, Minneapolis, Minnesota, USA) guided and assisted the close-out process of Neuromod’s clinical trial.

The tinnitus treatment device, now branded as Lenire®, which was used in the study was developed by Neuromod and consists of wireless (Bluetooth®) headphones that deliver sequences of audio tones layered with wideband noise to both ears, combined with electrical stimulation pulses delivered to 32 electrodes on the tip of the tongue by a proprietary device trademarked as Tonguetip®. The timing, intensity and delivery of the stimuli are controlled by an easy to use handheld controller that each participant is trained to use. Before using the treatment for the first time, the device is configured to the patient’s hearing profile and optimised to the patient’s sensitivity level for tongue stimulation.

For the trial, participants were instructed to use the Lenire® device for 60 minutes daily for 12 weeks. Out of 326 enrolled participants, 83.7% used the device at or above the minimum compliance level of 36 hours over the 12-week treatment period. For the primary endpoints, participants achieved a statistically and clinically significant reduction in tinnitus symptom severity.

When treatment was completed, participants returned their device and were assessed at three follow-up visits up to 12 months. 66.5% of participants who filled out the exit survey (n=272) affirmed they had benefited from using the device and 77.8% (n=270) said they would recommend the treatment for other people with tinnitus.

Participants in the study were screened and selected based on a pre-defined list of inclusion and exclusion criteria to ensure the trial had a wide distribution sample of the tinnitus population. More information on the criteria can be found on https://www.clinicaltrials.gov/using the identifier NCT02669069 and the full paper can be accessed here: https://www.neuromoddevices.com/tenta1results

Dr Ross O’Neill, Founding CEO of Neuromod commented: “We are delighted to announce the publication of positive results from our TENT-A1 clinical trial, which has shown significant improvements in tinnitus symptoms in patients using our unique Lenire® device. There is a globally recognised clinical need for evidence-based treatments for tinnitus, such as Lenire®, due to the lack of effective options for this debilitating condition. Neuromod is proud to be at the cutting edge of efforts to research and develop new solutions that can contribute to solving this chronic condition that affects 10-15% of the population worldwide. We are committed to continuing our research in the field and to advance our unique chronic tinnitus treatment technology”.

Hubert Lim, Chief Scientific Officer of Neuromod commented: “I am truly proud of our Company’s ability to perform such a large-scale randomised clinical trial in two countries, enrolling 326 participants to demonstrate the safety and efficacy of a new solution for tinnitus. This study tracked the post-treatment therapeutic effects for 12 months, which is a first for the tinnitus field in evaluating the long-term outcomes of a medical device approach. The outcomes are very exciting and I look forward to continuing our work to develop a bimodal neuromodulation treatment to help as many tinnitus sufferers as possible.”

 

At my first appointment at Neuromod, I was told that, in fact, Lenire was a tinnitus management device. I find the post above bordering on being fraudulent. It will certainly reinforce "positivity" and confirmation bias here on Tinnitus Talk.

I have yet to see one compelling story about improvement from using this device.

 

Attached is the full paper the above infographic was based on.

Any science gurus here to validate how BS it is?

 

My first impression is that the results are strangely at odds with the reported results from users on this forum.

Something like 85% of the participants of this study saw tangible improvement. I find that hard to believe. At first glance I could not see how the study mitigates the placebo effect either.

But as I have stated, "positivity" and confirmation bias will get a boost from this study.

 

This is actually a primary concern that Richard Tyler, audiologist at the University of Iowa, alludes to in the piece above that @spedgas linked to:

"the investigation had some notable shortcomings, however. The most concerning was the lack of a control condition in which some participants would not receive any therapeutic stimulation to rule out placebo effects."

Tyler's additional comment is in some way more salient:

"Another limitation was that the authors did not report whether the subjects experienced a reduction in tinnitus—actual changes in the perceptions of the phantom sounds. You have tinnitus, and you have your reactions to tinnitus. Those are two different things. If you're going to try and decrease the tinnitus, then you should be measuring the tinnitus.”

 

That is a point of uttermost importance. Habituation, "positive thinking", the need to justify an expensive treatment etc. makes for a perceived lowering of the bothersome aspects of tinnitus even tough the loudness and intrusiveness remains unchanged. At least for sufferers with mild tinnitus. Which, in my experience leaves Lenire as an expensive and dangerous habituation device. Just like the thousand of "tinnitus treatments" marketed by cynical entrepreneurs over the years. The "science" with the fusiform cells and that sort of scientific lingo is nothing more than a cloak to hide basic monetary aspects.

 

They should build a regression model to show what type of patients get the most benefit. This is very old fashioned ”all tinnitus patients are the same” type of paper.

Of course it might be in the company’s best interest to not do this as it would reduce the number of possible clients.

 

I thought they also checked Minimal Masking Level and found an average reduction of said MML. That's why I was initially quite hopeful, as for the first time a treatment could actually boast a measurable reduction in the loudnessof tinnitus, rather than the vague THI score improvements we have seen all too often in the past.

THI reduction is likely to happen if you give people the impression that you're treating them.

But without peer review they can claim whatever they want.

Speaking of which: is that peer review still coming or what? It's beyond laughable.

 

I think hell will freeze over before that peer review paper comes out.

If the clinicians can move beyond MML (which I believe is often flawed due to various reactions to sound we can have), and THI, which is clearly a psychological metric then I think we're going to reach a more "honest" situation where treatment is concerned.

Susan Shore's recent comments about measuring neuronal activity, which can be elevated in hyperacusis patients were quite interesting. If the same metric can eventually be applied to actual tinnitus then there's going to be no doubt about whether a device works in the physical sense or not. It's also going to prevent that situation where a person's psychological improvement over time is credited to said device instead of "habituation" (so-called )

 

This Lenire paper from these experts is just another one of obscenely obvious marketing techniques where what we have seen them do is put together a paper which has seemingly come from an expert position, but it is actually meant to try to talk up the benefits of Lenire.

This is incredibly identical to that article that was put out about FX-322 and Frequency Therapeutics a month or so ago that actually criticised their trial results by trying to talk them down and actually used experts in this field who were against it. It turned out that there was a similar connection to these experts in the FX-322 article and the ones used in the Lenire paper (head of their research) as it turned out that in both situations the experts had vested interests directly related to and influenced by both treatments.

Thus I take what we have seen in this article with a grain of salt and actually am almost certain that there will never end up being a well supported peer reviewed article on this because it is isn't going to be supported by anyone with any integrity in this field.

For a head of a company department to come out with this research and actually attempt to pass it off as Lenire being indisputably valid and extremely effective is simply laughable.

I also think that the reason that we are not seeing the same sort of criticisms towards Lenire as we have been by some who don't like the prospect of FX-322 succeeding is because Lenire isn't a threat and will not treat the underlying cause(s) like regenerative hearing medicine will which will ultimately reduce the benefit of those who have a vested interest in the current "treatments".

I think that this Lenere article is truly rubbish, however I think that in the long term we won't see much criticism towards it because basically it is not a threat to the status quo within the industry like OTO-413 or any other type of regenerative hearing medicine might be.

 

Has anyone heard/read anything about this?

https://newatlas.com/medical/neuromod-devices-lenire-tongue-ear-tinnitus/

 

Yes this whole thread is about Lenire.

Many people are questioning the benefits of this treatment and are actually not interested in it. I think that Lenire is being given a lot of marketing effort at the moment mostly because it is ineffective and it is not necessarily a good example of a tinnitus device.

I think that there will definitely be more success with regenerative hearing medicine and also actually with the University of Michigan (Susan Shore) device than with Lenire.

 

Sorry for the dumb question but does Lenire require pitch-matching to your tinnitus?

Mine is all over the place so assuming it works at all wondering if that would be an exclusion criteria for me.

 

There are like 4 people in the most recent Lenire User Experiences page (separate thread) who said it helped them.

 

No pitch matching. Just an audiogram.

 

Thanks. If you have a good audiogram, I wonder if you can still give it a try. My audiogram is flat and "normal" up to 8 kHz but am still interested in the device.

 

I believe so. The only purpose of the audiogram is to make sure the audio stimulation portion of the treatment is tuned to your hearing profile.

 

This article appeared in a Belgian quality newspaper today. (I ran it through Google translate, some sentences may be a bit odd).

It was published with a promo picture of Lenire. It seems they are basing themselves on the published study.

—
Electroshocks to the tongue may decrease the ringing in the ears of people with tinnitus. The effect of the treatment can last up to a year.
Hilde Van den Eynde
Tuesday, October 13, 2020 at 3.25 am

The patients received light electroshocks through a clip on their tongue and at the same time heard a series of sounds through headphones. neuromod devices limited
People who suffer from tinnitus, or ringing in the ears, constantly hear annoying whistling or buzzing noises. The condition affects an estimated ten to twenty percent of the adult population. "The disease is difficult to understand," says Frederic Acke, nose, throat and ear specialist at UZ Gent. Sometimes people with tinnitus hear real sounds, such as the blood flow in their ear. But usually these are sounds that their environment does not perceive. Then the disease is (literally) "between the ears" and it is the brain that registers sounds that are not there. One possible explanation is that in response to hearing loss, the brain overcompensates for frequencies that the ear no longer perceives. "If these people get a hearing aid, the tinnitus can decrease," says Acke.

However, there is usually no explanation for the condition, which is therefore difficult to treat. Cognitive behavioral therapy, which teaches people to shift their attention from the annoying ringing in the ears to something else, is the only proven treatment. But the approach is labor intensive and usually only moderately relieves symptoms.

Cracking candy
That is why an international research team investigated whether the brains of tinnitus sufferers can be put back on the right track with electroshock. They gave 326 patients light electroshocks through a clip on their tongues for up to an hour a day. That gave a slight tingling sensation on the tongue, like when eating "crackling candy". At the same time, they heard a series of sounds through headphones. The dual stimulation, auditory and sensory, was aimed at breaking the brain's fixation on sounds. This approach is called neuromodulation; it is also being tested against other brain diseases such as epilepsy or depression.

More than 80 percent of those undergoing electroshock treatment said they had improved
The experimental treatment lasted 12 weeks. During that time, the complaints of the participants decreased considerably, the researchers report in the well-regarded journal Science Translational Medicine. More than 80 percent of those who adhered to the prescribed treatment said they had improved. On a scale from zero to one hundred, their complaints decreased by an average of fourteen points. That effect lasted for at least a year, according to follow-up of the patients.

"That improvement is remarkably large," said Frederic Acke, who was not involved in the study. Cognitive behavioral therapy, the standard treatment for tinnitus today, does not achieve such high scores. However, Acke notes, there was no control group in the study. "That means the researchers can't know how many of the patients would have gotten better on their own. Comparison with a group that received the standard treatment, or no treatment, could have learned that. This is because placebo working plays a major role in tinnitus."

Too early
Acke also notes that not all subjects sustained the treatment for the full twelve weeks. "The researchers report a failure rate of 16 percent. They do not say why these patients dropped out. Did the approach not work for them? Did they find the electroshocks too difficult? That's what we guess."

The study was funded by the company that markets the electroshock device, Acke points out. "Several of the researchers are associated with this company. That does not mean that the study was not carried out correctly, but that there are more than just scientific interests at play."

In any case, there is solid science behind the starting point of the study, says Acke. "We know, for example, that neuromodulation can alleviate the complaints of people with depression or epilepsy. But it is still a bit too early to recommend treatment with electroshock to people with tinnitus."

 

Hello,

I had a read through of both the “Science Translational Medicine” paper, and the “Scientific American” article.

My notes and observations:

1. One of the main concerns of the study is the comparison of the effectiveness of the three Arms i.e. which is best and a speculation as to why? Unfortunately it doesn't give much consideration to the question of whether the treatment in any of the arms is effective at all. That is, there is no comparison (but also see 2) against a control and in actual fact, they could all be equally ineffective. Given that tinnitus treatments can have very strong placebo effects, and the fact there is not much difference between the arms, I think this is a glaring omission. There's no point in comparing effectiveness of arms if it isn't clear that they actually have an effect. This flaw is mentioned in the Scientific American article.
2. They did notice a difference between the arms at 12 months, and used this as evidence to counter placebo effects. However, the difference is quite weak at 12 months (e.g. it was not significant using Fisher's exact test).
3. The paper reports the % of participants who improved when using the treatment, where improvement is deemed to occur when TFI (or THI) is reduced. Naively an improvement rate of 86% looks very good. But this is quite misleading as a small reduction in TFI (say 1 point) should not be considered an improvement. Most of these scales have an MCID (a delta which is considered significant). While MCID was used in the leaked report, it is not used here.
4. They noticed significantly more improvement in TFI/THI for those with higher baseline TFI/THI. We looked at this in the Tinnitus Talk Lenire User Experience Group study and found no such relationship (but our sample size was much smaller!).
5. In the Dr. Susan Shore study treatment, the frequency of the tones is matched to the participant's tinnitus frequency, whereas this is not the case in this treatment. In this study, they looked at the extent of reduction in TFI/THI and the extent to which the hearing loss frequency matched the tones in the treatment (Arm3 used very much lower tones). They found no relationship. Or in other words, they are saying that matching the tones in the treatment with the participant's hearing loss appears to offer no benefit.

I think the main issue here is the lack of a control. Placebo effects are a major issue with tinnitus studies and I think any conclusions about the effectiveness of a tinnitus treatment are not possible when the study design cannot be used to rule out placebo effects. This is the case here, so I think it's not possible to say if Lenire works or not...

 

I conclude from your points that Neuromod's sole aim was to make their report and thus Lenire as marketable as possible.

It's a shame a reputable researcher like Hubert Lim would agree to such tactics. Where's the ethics?

 

I think that it is quite obvious Neuromod is trying to sell Lenire and nothing else. Hence why this study has already been canned on a number of different platforms.

I'm pretty sure that this seems like their window to try and sell Lenire which could become obsolete next year if Dr. Shore’s device is better and/or regenerative drug treatments work.

 

To tommyd87:

Very perceptive - as far as I am concerned, this was no more than Desyncra Redux.

 

I think the reality is all those researchers have sold themselves out and the same goes with that science magazine that published the article (though it looks like its reputation is really poor right now).

 

Susan Shore often seems to use the word "ethical" when referring to her particular line of research. I wonder why?

 

To UKBloke:

Perhaps by "ethical" her intention is to be very careful so that there are no accidental neuralgic activations of the Trigeminal Nerve, which in a few reported instances during Lenire's usage resulted in horrific consequences.

I thought that tinnitus was nightmarish, but such Trigeminal Nerve activation is actually so painful that it's entry on line states that "It is often called the Suicide Disease."

I briefly described Lenire to my ENT Doctor, and (paraphrasing him) he said that if you thought tinnitus was an abyss in Hell, Trigeminal Nerve pain was surpassingly worse.

 

I don’t know whether it is due to the fact that there is a large ethical/ethics component of the research she has to do. Alternatively it could be due to the truthful fact that she wants the device to work well with best outcomes being delivered such as ensuring it is a valued product and truly assists tinnitus patients broadly.

Dr. Susan Shore’s device is probably not going to be anything like Lenire. Her research will be peer reviewed and have a lot more validity to it.

 

But you will find no one from the earlier Lenire users saying the same, leaving new updates, praising the efficacy. Why do you think that is?