Assessment of compliance and satisfaction with a self-adjusting bimodal neuromodulation device and virtual follow-up visits used for tinnitus

Abstract

Tinnitus can negatively impact quality of life for many who experience it, leading to an urgent need for viable treatment options. Tinnitus treatments can vary in quality, validity, and success rates. One method that has shown prior success in clinical trials to reduce the bothersome degree of tinnitus is bimodal neuromodulation, such as with the Lenire treatment device. However, this is not without certain barriers when looking at access to care. Clinicians who treat tinnitus may not be in convenient locations for patients to frequently travel or may not have experience working with people who have tinnitus. One way to reduce this problem, would be to provide fully virtual follow-up sessions, limiting the need for patients to come to clinics. Additionally, another way would be to not “fit” treatment devices based on hearing loss, but to use standard settings for all while allowing suprathreshold adjustments by the user based on comfort. This usability assessment study investigates how making these clinical modifications to the previous Lenire device impacts compliance to the treatment and satisfaction in using the device, as well as tinnitus severity outcome measures. After 12 weeks of device use, compliance and satisfaction remained high as seen in previous studies and many participants had changes that met the level of minimal clinically important difference on tinnitus severity questionnaires. The positive therapeutic outcomes of the study did not differ from previous reports using bimodal neuromodulation for tinnitus, despite simplifying the fitting process for the bimodal neuromodulation treatment, not requiring personalized audiogram settings, and use of virtual follow-up sessions instead of requiring in-person visits. These findings open up opportunities for broader accessibility and scalability of treatment options, such as bimodal neuromodulation, for tinnitus patients.

Clinical trial registration:

clinicaltrials.gov/study/NCT05518682, identifier: NCT05518682.

1 Introduction

Tinnitus is the perception of sound that does not have an external source, commonly described as ringing in the ears (National Institute on Deafness Other Communication Disorders, 2023; Esmaili and Renton, 2018), and affecting approximately 10–15% of the global population (Henry et al., 2005; Jarach et al., 2022). Tinnitus symptoms can be bothersome to those who experience them, leading to distress and reports of reduced quality of life (Langguth et al., 2013). Treatment options for tinnitus include hearing aids, sound therapy, and cognitive behavioral therapy, which have varying degrees of success (Czornik et al., 2022; Tang et al., 2019).

Tinnitus is thought to be a result of maladaptive changes in neural firing of one or several regions in the brain. It has been hypothesized that changes in the central auditory system cause reduced inhibition in central auditory structures leading to hyperexcitability (Baguley et al., 2013; Eggermont and Roberts, 2004). Changes may include loss of peripheral input, changes in synchrony of neural firing, altered spiking patterns, tonotopic reorganization, and hyperactivity (Baguley et al., 2013; Eggermont and Roberts, 2004). To address this maladaptive firing that may be leading to the perception of tinnitus, the use of neuromodulation has been considered. Neuromodulation is defined as the alteration of nerve activity through target delivery of a stimulus, such as electrical stimulation or chemical agents to a specific neurological site in the body (International Neuromodulation Society, 2018). Bimodal neuromodulation is altering nerve activity using stimuli of two different sensory modalities at the same time (International Neuromodulation Society, 2018; Gloeckner et al., 2022). Bimodal neuromodulation, with a combination of sound and electrical stimulation of different body regions, such as the tongue, has shown modulatory effects in the auditory system, changing the firing rate or patterns of auditory neurons over the course of stimulation (Gloeckner et al., 2022; Markovitz et al., 2015). Commercial devices are currently available with several clinical trials having been completed (Lenire., 2024; Markovitz et al., 2015). Their results have shown positive effects when evaluating bimodal neuromodulation compared to sound-only stimulation, with patients reporting a decrease in the bothersome nature of their tinnitus on questionnaires including the Tinnitus Handicap Inventory (THI) and the Tinnitus Functional Index (TFI) following 12 weeks of bimodal neuromodulation device usage (Boedts et al., 2024; Conlon et al., 2020; Conlon et al., 2022; Hamilton et al., 2016).

Previous iterations of bimodal neuromodulation devices have required in person visits and personalized fittings and adjustments by a hearing healthcare professional, either an audiologist or hearing technician (Conlon et al., 2019). Patients would use the device for 60 min per day at home, but would meet with their hearing healthcare professional in office for adjustments to the device. The novel objective of the current study was to reduce barriers to access to care by allowing for virtual follow-up visits and programmatic changes to be made virtually by the participants with verification by a researcher, and allow individual changes to electrical stimulation levels and auditory stimulation levels without the need of a customized audiogram-based fitting of the device. These are important in making the device accessible to those not within reasonable driving distance to a clinic and giving our participants more control over the settings that may allow them to take more charge of their treatment. In addition to reducing barriers to accessible tinnitus care, this model may also streamline use of the device, allowing for more tinnitus patients to be treated with the device, without specific programmatic settings made by a professional who treats tinnitus. Programming the device to the person's audiogram was intended to ensure audible acoustic stimulation to the listener at the tested hearing thresholds (250 Hz to 8000 Hz); however, our intention is to test the bimodal neuromodulation device without this requirement by instructing the users to set the volume of the acoustic stimulation to a level that is comfortable and audible. This change can allow the device to be used directly out of the box while potentially allowing them to still see improvement in their tinnitus symptoms. The study was designed to evaluate the potential of these clinical changes which could then be implemented into the current standard clinical treatment protocol.

In order to evaluate our proposed clinical methods, we assessed usability of the device by measuring compliance and satisfaction, as well as evaluating standard outcome measures of tinnitus severity. These results are compared with the results from previously published large-scale clinical trials using the same neuromodulation device. We assessed compliance across 12 weeks of device usage through data logging on the neuromodulation device. We also asked participants two questions after their 12 weeks of device usage to assess their satisfaction with the device and their perceived benefit from the treatment. Lastly, we collected several patient-reported outcome measures (PROMs), which evaluate tinnitus severity, tinnitus loudness, and a variety of mental health aspects that may be associated with tinnitus. We hypothesized that using a virtual care model, allowing for self-adjustments of the acoustic and electrical stimulation, and not applying audiogram-based programming to the device, would show equal or higher levels of compliance, satisfaction, and improvements to tinnitus, compared to previously reported large-scale clinical trial data that used a more standard clinical, in-person treatment model.

2 Methods and materials

2.1 Recruitment and participants

Ethics approval for this study was obtained by the University of Minnesota (U of M) Institutional Review Board (STUDY00015524). Written informed consent was obtained for all participants using electronic signatures and stored in REDCap. We completed a usability assessment study investigating compliance and satisfaction of a portable hand-held bimodal stimulation device. This study was completed through in-person visits at the U of M and virtual care visits (Zoom).

To be included into the study, participants needed to be at least 18 years of age, have subjective non-pulsatile tinnitus for greater than 3 months but less than 20 years, have a Tinnitus Handicap Inventory (THI) baseline score between 38 and 76 (described as moderate to severe tinnitus), and hearing thresholds less than 90 dB HL at 250, 500, and 1000 Hz. They were excluded if they had middle ear disease or fluctuating otologic conditions, hyperacusis or misophonia, or had initiated, ceased, or changed use of a prescription medication in the prior 3 months that may impact the outcome (including antidepressants, anticonvulsants, neuroleptics, or opioid analgesics). All health history and medication questions were self-reported through case history questionnaires. A full list of additional inclusion and exclusion criteria can be found at clinicaltrials.gov (NCT05518682).

Participants were initially recruited throughout the United States from a variety of sources including clinicaltrials.gov, company newsletter, the U of M StudyFinder website, and word of mouth. Due to challenges with scheduling in-person visits on the U of M campus, recruitment was limited to Minnesota residents halfway through this study. Participants were required to fill out an initial screening questionnaire through REDCap, and participants who met the initial inclusion/exclusion criteria were invited to attend an in-person visit at the U of M to determine final eligibility for the study. During this initial eligibility visit, responses to the health history and medication questions were reviewed. Participants also completed a series of tinnitus-related questionnaires and an audiologic screening, which consisted of air conduction thresholds at 250, 500, 1000, 2000, 3000, 4000, 6000, 8000, 10000, and 12000 Hz. This testing was completed using a GSI Pello audiometer connected to GSI AMTAS software (Grason-Stadler, Eden Prairie, MN) using Radioear DD450 circumaural headphones. The audiometer was calibrated using ANSI 3.6 (2010) standards. Audiometric eligibility criteria allowed us to ensure participants could receive sufficient audibility within the devices' current indications for use.

We screened 348 potential participants for inclusion and exclusion eligibility criteria. We invited 46 participants to come for an in-person visit, and 26 who met the final eligibility criteria were enrolled in the study. Participant were placed into one of two groups, low hearing loss or high hearing loss. The low hearing loss group had hearing thresholds less than 40 dB HL at 250, 500, 1k, 2k, 3k, 4k Hz and the high hearing loss group had hearing threshold that exceeded that criterion in one or more of the frequencies, unilaterally or bilaterally. Our goal was to have at least 4 participants in each of these groups to allow us to analyze data in a group of participants with a range of hearing abilities. We enrolled 17 people into the low hearing loss group and 9 people into the high hearing loss group. Additional participants were enrolled compared to our initial recruitment goal of 20 participants to account for withdrawals from the study. Throughout the study, three individuals dropped out, and two individuals began taking exclusionary medications leading to their results being ineligible for data analysis. Therefore, 21 participants completed the study, as shown in the study flow diagram in Figure 1.

Figure 1

2.2 Tinnitus assessments

Participants were screened using a variety of questionnaires for tinnitus severity and mental health, including the THI, TFI, Visual Analog Scale—Loudness (VAS-L), Patient Health Questionnaire—8 (PHQ-8), Perceived Stress Scale—10 (PSS-10), and Generalized Anxiety Disorder—7 (GAD-7). In this report, we will focus on the tinnitus specific outcome measures of THI, TFI, and VAS-L, where a future publication will present results for the other mental health related outcomes.

The THI is a self-reported measure with 25 questions used to measure severity of tinnitus (Kleinstäuber et al., 2015; Newman et al., 1996; Zeman et al., 2011). Each question about tinnitus is answered either “yes”, “sometimes”, or “no”, and these answers were given a point value. The total score for the 25 questions is between 0 and 100 points. The total score places the person in a tinnitus severity category including slight or no handicap, mild, moderate, severe, or catastrophic. Criteria for eligibility in the study on the THI ranged from a score of 36 to 78, which corresponds to a moderate or severe tinnitus severity. This questionnaire is commonly used in clinical practice for tinnitus and has a minimum clinically important difference (MCID) of 7-points (Zeman et al., 2011).

The TFI is a self-reported questionnaire with 25 questions to assess severity of tinnitus as well as its impact on daily functioning (Henry et al., 2016; Meikle et al., 2012). These questions involve rating each question on a scale of 0 to 10 with a total score for the 25 questions being between 0 and 100. The total score can indicate symptom severity, although this questionnaire includes a subcategory score for 8 different categories, including intrusiveness, sense of control, cognitive, auditory, sleep, relaxation, quality of life, and emotional. This questionnaire has been readily used clinically and has a MCID of 13-points (Henry et al., 2024).

The VAS-L is a rating scale where tinnitus loudness is subjectively rated on a continuum between 0 (inaudible) and 100 (extremely loud) (Adamchic et al., 2012; Raj-Koziak et al., 2018). The MCID for this questionnaire is a change of 10–15 points in the value assigned for perceived tinnitus loudness (Adamchic et al., 2012). For a conservative assessment, we used a 15-point change as the MCID.

2.3 Study intervention

The bimodal neuromodulation device used in this study was the Lenire device, by Neuromod Devices (Dublin, Ireland). At the time of this study, the device was not approved by the Food and Drug Administration (FDA); however, it had the CE marking in Europe and was being fit and sold clinically. This device stimulates the tongue with electrical pulses while auditory stimulation is being played simultaneously (Lenire., 2024). The standard protocol involved fitting the device based on current hearing thresholds and required in-person follow-up sessions. Traditionally, this device is custom-programmed by a hearing professional based on individuals' audiograms and all follow-up visits were attended in-person. With that approach, the auditory stimulation was programmed to +10 dB SL relative to their hearing threshold from 250–8000 Hz (Conlon et al., 2020). Patients had a limited range of device adjustment options. We were looking to assess if self-adjusted global audibility across frequencies was sufficient to lead to a therapeutic outcome, in which we did not specifically assess if the sound stimulus was audible for each frequency. Based on prior studies, our study was designed to use two different settings (Parameter Sets, PS) on the device. The first setting (PS1) provides synchronous stimulation between the electrical and acoustic stimulation. The acoustic stimulation contains pure tone bursts between 500–8000 Hz with a background wideband noise. The electrical stimulation is delivered to the tongue array at a specific location depending on the pure tone frequency. During the second 6 weeks, participants used the setting PS4, in which the electrical and acoustic stimulation were presented in a semi-synchronized fashion, with random 0–30 ms delays between the presentation of the electrical stimulus and the acoustic stimulus. These two device settings were chosen to vary stimulation during the 12 weeks to attempt to avoid any plateau effect of prolonged stimulation and to help drive further therapeutic neural changes from device use, as was demonstrated in a previous clinical study using the same two device settings (Conlon et al., 2022).

After consent and eligibility determinations, participants were given the bimodal neuromodulation device during the first visit and were trained in how to use the device. They were also given time during this visit to practice and ask questions. Participants were instructed to use the device for 30 min, two times per day or one time per day for 60 min. They were allowed to choose whichever worked better for their schedule. After their first enrollment visit, participants followed up with a member of the study team by phone at 1 week to discuss any questions that may have come up after trying the device at home for the first 7 days. Participants then completed a zoom call at week-6, at which time THI, TFI, VAS-L, and additional usability questions were answered. During this visit, participants were instructed to change their device from PS1 to PS4. They completed this while on the video call, and the device was confirmed to be in the new settings by a research team member. A follow-up phone call was completed 1 week later, week-7, to confirm no questions arose following the change in stimulation setting. Then participants participated in a video visit at week-12 and completed THI, TFI, VAS-L, and satisfaction questions; along with the PHQ-8, GAD-7, PSS-10, and additional usability questions. Afterwards, the device was shipped back to the study team. The PHQ-8, GAD-7, and PSS-10 results will be analyzed further and presented in a future publication relating tinnitus to other mental health characteristics and disease conditions that is outside the scope of this paper. The final step was a follow-up 12 weeks after they ceased using the device, at 6 months. The THI, TFI, VAS-L were completed again at this timepoint. During each visit, a study team member asked questions about medication changes, checked if there were any problems with the device, and monitored any adverse events that were brought up by the participant. See Figure 2 for a timeline of study events.

Figure 2

2.4 Outcomes

The primary objective of the study was to assess usability of the self-adjustable Lenire device through assessment of compliance and satisfaction of device usage by the participants. The primary outcome for this study was compliance with the device over 12 weeks of treatment. Data collected from the devices consisted of timestamps to indicate when the device was turned on/off and when the play, pause, volume up/down, and electrical intensity up/down were pressed. This tracking allowed us to capture the dates and time, amount of time the devices were used and any adjustments that were made with the device. Based on previously reported results, which indicated 36 h of usage over 12 weeks was sufficient to observe improvements in tinnitus (Conlon et al., 2020, 2022; Boedts et al., 2024; Hamilton et al., 2016), we classified a participant as compliant if they used the device for a minimum of 36 h. Participants were made aware of study outcomes and device data tracking to measure compliance during study enrollment and consent.

The secondary outcome for this study was satisfaction in using the Lenire device. Two satisfaction questions were asked at the end of device usage at 12 weeks, which included “If you knew someone with tinnitus would you recommend they try this device?” and “Overall, would you say you have benefitted from using this device?”, to which participants would answer “yes” or “no”. Additional exploratory usability questions were included in the 6-week visit and the 12-week visit. These questions included “Do you think the treatment in its current form (device and duration of sessions) is suitable for long term use?” and “How did you find fitting the treatment regime into your existing daily routine?”, to which participants would answer “yes” or “no”; or “easy”, “manageable”, or “difficult”, respectively.

Additional exploratory tinnitus severity outcome measures include the THI, TFI, and VAS-L.

Safety was monitored throughout the treatment duration as well. Adverse events were recorded and are reported in this paper. Device safety has previously been monitored comprehensively by the device manufacturer; however, our intent is to determine if changing the fitting protocol and self-adjustment settings impacted adverse events in our overall participant population.

2.5 Statistics

THI, TFI, and VAS-L scores (exploratory endpoints) were collected at week-0 (baseline), week-6, week-12, and week-24 (also known as the 6-month visit), and comparisons between timepoints were completed to measure changes between these scores within our population. An unequal variance t-test (Ruxton, 2006) was completed on the mean change in score from baseline to week-6, baseline to week-12, baseline to 6 months, week-6 to week-12 and week-12 to 6 months at the group level. We also calculated the 95% confidence interval for the average change between timepoints, and Cohen's d to show the effect size between the mean group scores at different timepoints. Since THI, TFI, and VAS-L were all exploratory outcome measures, multiple comparison correction was not implemented; instead, the p-values and effect sizes are listed for further interpretation of the outcomes.

3 Results

3.1 Study overview

Recruitment began in September 2022 and ended in August 2023. During this time, 26 participants were enrolled in our 6-month study. See Figure 1 for a flow chart of enrollment and recruitment. Table 1 shows the demographic characteristics of the 26 enrolled participants. Audiometric data for enrolled participants is depicted in Figures 3, 4. Not all participants had symmetric hearing. One participant had 15–30 dB HL threshold differences between 2000–8000 Hz. Some other small asymmetries are observed as well. Three participants withdrew from the study. Two of the withdrawn participants reported concerns about fluctuating tinnitus, and one participant no longer had time for the study. The remaining 23 participants (88.4%) completed the full study duration. An additional two participants were excluded from final analysis on the basis of changing neuroactive medications during the study, leaving us with 21 total participants (80.8%). Compliance, satisfaction, the additional usability questions, and other tinnitus outcome measures of THI, TFI, and VAS-L are reported for the 21 participants who completed the study. All 26 enrolled participants are included in the safety section. Since the sample size was small for the low hearing loss group (n = 14) and high hearing loss group (n = 7), and we did not observe any noticeable differences in outcomes across the two groups; therefore, we performed analyses on the full cohort for this study.

Figure 3

Figure 4

3.2 Primary and secondary outcomes

The primary outcome data for compliance showed that 20 out of 21 participants were compliant with using the device for a minimum of 36 h over 12 weeks of treatment. The group average usage was 67.88 h (SD, 21.13) over 12 weeks with compliant participants using the device between 38.88 h and 85.38 h (Figure 5). The non-compliant participants used the device for 6 h during the 12 weeks.

Figure 5

For the secondary outcome of satisfaction rates at week-12, 19 of 21 (90.5%) participants stated “yes” that they would recommend this device to someone they know with tinnitus, while 14 of 21 (66.7%) participants stated “yes” that they received benefit from this device.

3.3 Additional usability questions

Two additional usability questions were asked to the participants at the 6-week and 12-week timepoints for exploratory analyses.

On the 6-week usability questionnaire, results showed 17 out of 21 (81%) participants answered “yes” that they thought the treatment was suitable for long-term use and 19 out of 21 (90.5%) participants reported “easy” or “manageable” for fitting the treatment into their daily routine. On the 12-week post-device usability questionnaire, 17 out of 21 (81%) participants responded “yes” and 18 out of 21 (85.7%) participants reported it was “easy” or “manageable” to the same questions, respectively.

Some participants changed their opinion to the usability questions over time. For the question “How did you find fitting the treatment regime into your existing daily routine?” 14 out of 21 (66.7%) participants felt the same at the 6-week visit and 12-week visit, 4 participants changed their responses from “easy” to “manageable,” 2 participants changed their responses from “manageable” to “difficult” and 1 person changed from “difficult” to “easy”. For the participants who reported it was “difficult” to fit the treatment into their existing daily routine, these participants reported that the treatment was too long, they were too busy to find time, or they just kept forgetting to do it.

Responses for the usability question “Do you think the treatment in its current form (device and duration of sessions) is suitable for long term use” did not change for any participant between the 6-week visit and the 12-week visit.

3.4 Tinnitus outcomes

Results and statistical analyses are reported in Table 2. Scores that are reported as negative numbers signify that the score at baseline (or the earlier time point) is higher than the score at the later time point, and thus there is an improvement in reported tinnitus severity over time. THI, TFI, and VAS-L scores were analyzed as the difference in score from week 0 to week 6, week 0 to week 12, week 0 to 6 months, 6 weeks to 12 weeks, and 12 weeks to 6 months (Table 2). Results for 0 to 12 weeks and 0 to 24 weeks were planned exploratory analysis and showed average improvements (reductions in score) exceeding the MCID. Additional post-hoc analyses were completed to further assess how these different tinnitus outcomes changed over time. Post-hoc analyses included outcome results from the first 6 weeks (week 0 to week 6), the second 6 weeks (week 6 to week 12), and the 12 weeks following device use (weeks 12 to 24).

The mean change in THI from week 0 to week 6 was −16.9 points, from week 0 to week 12 was −19.5 points, from week 0 to 6 months was −21.1 points, from 6 weeks to 12 weeks was −2.7 points, and from 12 weeks to 6 months was −1.6 points. Individually, participants showed changes on the THI over the 12 weeks of device usage ranging from +6 and −54 with these results shown in Figure 6, and 81% of participants showed a clinically meaningful improvement in tinnitus symptoms exceeding a MCID of 7 points.

Figure 6

The mean change in TFI from week 0 to week 6 was −14.2 points, from week 0 to week 12 was −17.3 points, from week 0 to 6 months was −17.2 points, from 6 weeks to 12 weeks was −3.1 points, and from 12 weeks to 6 months was +0.1 points. Individually, participants showed changes on the TFI ranging from +12 and −44.4 over the 12 weeks of device usage with these results shown in Figure 7, in which 66.7% of participants showed a clinically meaningful improvement in tinnitus symptoms exceeding a MCID of 13 points.

Figure 7

For the VAS-L, there were 4 missing data points, so the averages were calculated out of a group of 16 participants (Table 2). Average group change in VAS-L from week 0 to week 6 was −15.7 points, from week 0 to week 12 was −16.7 points, from week 0 to 6 months was −6.4 points, from 6 weeks to 12 weeks was −1.1 points, and from 12 weeks to 6 months was 10.3 points. Individually, participants showed changes on the VAS-L ranging from +15 and −45 over the 12 weeks of device usage with these results shown in Figure 8, in which 58.8% of participants showed a clinically meaningful improvement in reported tinnitus loudness exceeding a MCID of 15 points.

Figure 8

3.5 Adverse events

We monitored participants for any adverse events (AEs) throughout the duration of the study. Participants were given a list of potential side effects that have been previously identified in prior clinical trials using the Lenire device. This list included, but was not limited to, fluctuations in tinnitus, jaw pain, dry mouth or excess saliva, tooth sensitivity, tongue discomfort, ear pain, or nausea. This table was listed in the consent document, so participants were aware of possible AEs prior to consenting to the study. AEs were primarily reported during the first 5 days following enrollment into the study; however, we also noted an increase in AE reports following the program changes at the week-6 visit and the following week-7 check-in call. Out of our 26 participants who were enrolled, 18 (69.2%) participants reported one or more adverse events during this study. Of these 18 participants, all 18 (100%) reported a tinnitus fluctuation. When this AE was reported, participants were asked if they felt comfortable to continue. If they were bothered by the temporary increase in tinnitus, participants were instructed to turn the volume down on the device and see if that helped to return their tinnitus to baseline. If it was uncomfortably bothersome, participants were instructed to stop using the device for 5 days after which a follow-up was conducted again to see if the tinnitus had returned to baseline. They were either instructed to return to normal use (with lower volume if needed) or we repeated the 5 days without device use and rechecked if tinnitus loudness persisted. For most (14 of 18, 78%) participants reporting a tinnitus fluctuation, the change in tinnitus loudness was short-lived, resolving between a few minutes and a few days. However, one participant reported a fluctuation lasting 1 month, 1 participant reported a fluctuation lasting until the completion of the study, and 2 participants withdrew due to tinnitus fluctuations.

Other reported adverse events were tinnitus pitch change, sound sensitivity, excess saliva, muscle twitch, neck/jaw pain, tongue tingling, and ear popping. Table 3 shows a detailed report of number of AEs reported for each symptom. These adverse events were all documented; however, many participants reported outside factors possibly contributing to the symptoms, including migraines, a cold or other sickness, allergies, noise exposure, and daily work stress.

3.6 Discussion

The goal of this exploratory usability assessment study was to investigate device usability through assessment of compliance and satisfaction, as well as several tinnitus outcomes with a bimodal neuromodulation tinnitus treatment device using a novel fitting approach. This approach was modified to streamline and simplify the fitting and assessment process. We compared results to previous large-scale clinical trial data in order to evaluate our approach and confirm that it does not negatively impact the participant's experiences with the Lenire device. Our study design did not require device fitting to account for for hearing thresholds but instead allowed for individuals to adjust acoustic stimulation levels based on comfort and self-determined audibility during treatment; therefore, there was no standard sensation level across frequencies. We also completed all follow-up visits virtually, including changing settings, troubleshooting the device when needed, and answering questions. We anticipated that these changes could help to reduce some potential barriers to using the device, as some people may not have access to go to a clinic's physical location for help or assistance, but could easily join a virtual call from home when needed. Among individuals who remained in the study for 12 weeks, the device use compliance rate was 20 of 21 (95.2%). Self-reported benefit was 14 of 21 (66.7%). Based on our compliance data and the satisfaction questions that we asked participants, the results are similar to those observed in previous clinical trials, which show compliance to be approximately 82–84% for 12 weeks of device usage (Conlon et al., 2020, 2022). Previous studies showed that the participant self-reported benefit rate was 63–70% (Boedts et al., 2024; Conlon et al., 2020, 2022). Our results are in alignment with previous studies, which indicates that the changes in the protocol and simplification of the device fitting process did not impact the use or perception of benefit from the device. These results show that reduction of tinnitus severity from bimodal stimulation treatment can be observed under less controlled requirements than previously shown.

Success with virtual visits and self-programming of the device reinforces the value of virtual healthcare, which can reduce barriers in access to care for those far away from a clinic or who have mobility concerns. Self-fitting has been considered in other fields as well, including the fitting of hearing aids. Trials examining the self-reported outcomes of hearing aids (De Sousa et al., 2023; Knoetze et al., 2024; Perry and Nelson, 2022) conclude that self-fitting hearing aids show similar satisfaction and benefit when compared to audiologist-fit hearing aids (De Sousa et al., 2023; Knoetze et al., 2024).

Additional exploratory analysis demonstrated minimal clinically important improvements in several key measures of tinnitus severity, tinnitus impact on daily life, and loudness were achieved among a majority of study participants. There was an average decrease of 19.2 points on the THI when using the device for 12 weeks, surpassing the MCID on the THI of 7 points (Zeman et al., 2011). Sixteen participants had a decrease in tinnitus symptom severity on the THI of more than 7 points and 4 did not. For the TFI, the group mean change during the 12-week device usage was a decrease of 17.29 points, which is a larger change than needed to meet the MCID of 13 points (Henry et al., 2024). On an individual level, 13 participants had a decrease in tinnitus symptom severity of more than 13 points on the TFI and 7 did not. On the VAS-L, the mean decrease was 16.8, surpassing the MCID of 15 points on a 100-point scale (Adamchic et al., 2012). Individually, 9 participants had a decrease in reported tinnitus loudness of more than 15 VAS-L and 7 did not. One participant reported an increase in perceived loudness above a 15-point change between baseline and 12 weeks. The various tinnitus outcome measures, especially from week 0 to week 6 and to week 12, achieve a significance level with a p-value less than 0.05 using an unequal variance t-test, as shown in Table 2.

From our study findings, there are several interesting observations related to tinnitus treatment using the Lenire device. The self-reported benefit by the participants was 66.7% while participants willing to recommend the Lenire device to a friend reached 90.5%. This discrepancy suggests that participants may not have obtained benefit from the Lenire treatment but believe it is acceptable or safe enough with the potential to provide sufficient benefit in order to recommend others try it themselves. Another interesting observation was the self-reported benefit was 66.7% but we observed some differences in outcomes for THI, TFI, and VAS-L spanning 81%, 66.7% and 58.8% responder rate, respectively, supporting the multi-faceted dimensions of tinnitus and the importance of potentially leveraging multiple outcome measures to comprehensively assess tinnitus severity in patients in response to treatment.

3.6.1 Safety

Adverse events during the study were not unexpected, as previous work using bimodal neuromodulation has reported similar AEs as well. The majority of the reported AEs during this study were mild or not bothersome to participants and resolved quickly. Neither this study nor previous studies have reported any serious AEs related to the use of the Lenire device.

3.6.2 Limitations

This study was a small usability assessment study evaluating procedure changes in fitting and adjusting settings for a bimodal neuromodulation device. We were only able to recruit 26 tinnitus participants out of 348 screened individuals for this study. THI score was the major limiting factor for enrolling many potential participants. Our requirement of a moderate to severe score was important to our study design as it allowed for us to see changes in either direction by not allowing people into the study who had a THI score that was either too low or too high to exhibit a noticeable change over time. Some other primary reasons for ineligibility included not having tinnitus for a long enough duration (more than 3 months), taking exclusionary medications, or being a new hearing aid user (within the last 3 months).

A total of 21 participants completed the study. The small sample size limits demographic diversity, which can potentially limit the generalizability to other populations. Due to the small sample size, it was also not readily possible to perform sufficient sensitivity analyses or imputation methods to account for missing data, particularly the VAS-L. Encouragingly, the VAS-L trends were generally consistent with the THI and TFI results that did not have any missing data. Multiple statistical comparisons performed across THI, TFI, and VAS-L scores can also increase Type I errors, such that that the presented p-values for those outcome measures such that be interpreted as exploratory analyses.

Another limitation to this study was the lack of a control group and randomization procedure in the study design. Since the Lenire treatment device was already commercially available across Europe and broadly known by the tinnitus patient community via various social media outlets that the treatment involves suprathreshold sound and tongue stimulation, multiple participants in our study would have been aware if they were in a control group with no acoustic or electrical stimulation or if electrical stimulation was performed on a different location other than the tongue region. Furthermore, previous animal studies have demonstrated that bimodal stimulation can still be effective with electrical stimulation of different body regions (Markovitz et al., 2015; Wu et al., 2015); so future blinded clinical trials will need to consider other non-effective acoustic or electrical stimulation patterns as an active bimodal control condition. The design of this study is an exploratory, usability study investigating a modified fitting and monitoring approach of a previously reported device, in which it was still possible to show consistent outcomes to previously completed and published large scale clinical trials (Boedts et al., 2024; Conlon et al., 2020, 2022; Hamilton et al., 2016). Another consideration is the financial aspect that may impact someone's willingness to pursue a bimodal neuromodulation treatment device. For this study, participants were given the device to use at no-cost to them, but the cost of the device could limit the ability for a patient to try or recommend the treatment. Health insurance coverage for bimodal treatment can further expand access to a larger patient population, in addition to leveraging successful self-fitting and virtual care pathways for tinnitus treatment.

3.7 Conclusions

Compliance and satisfaction were not negatively impacted when using a novel fitting and treatment approach, which included virtual follow-up care and self-adjustable stimulation settings with a Lenire bimodal treatment device. Tinnitus severity and self-reported tinnitus loudness were also generally improved by using the device as intended on a daily basis for 12 weeks. Thus, the novel virtual fitting and remote follow-up procedure is promising for improving access to bimodal neuromodulation technology for a broad population of people suffering from tinnitus.

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