Promising Treatment for Tinnitus Shows Positive Results

Importance  

Animal models have shown altered dorsal cochlear nucleus circuitry in animals that develop tinnitus; However, precise treatment with bisensory stimuli (auditory and somatosensory) can reverse the altered neural patterns and reduce tinnitus.

Aim  

Confirm and extend the findings of a pilot study, which suggested greater efficacy of bisensory stimulation, to a clinical trial of longer duration and a larger number of participants.

Design, environment and participants  

This single-center, randomized, double-blind, crossover clinical trial was conducted in March 2019, with a 3-month follow-up per participant ending in July 2022. Eligible adults were recruited from the University of Michigan Health System. in Ann Arbor, Michigan.

Eligibility criteria included bothersome tinnitus (tinnitus functional index [TFI] score, ≥17 points), somatic tinnitus, normal to moderate hearing loss, and no other tinnitus treatment in the 6 months before the trial.

Enrolled participants were randomly assigned to treatment group 1, which received active treatment (bisensory), or group 2, which received control treatment (auditory only). Results were analyzed using intention-to-treat (ITT) and per-protocol (PP) populations.

Intervention  

The precisely timed bisensory (combined auditory and somatosensory) treatment was delivered via a personalized wearable take-home device that was provided to each participant for daily at-home treatments.

Participants in group 1 received 30 minutes per day of the bisensory treatment for 6 weeks, followed by a 6-week washout phase, and then 30 minutes per day of the auditory-only treatment followed by a second 6-week washout phase. Participants in group 2 first received the auditory-only treatment, followed by a washout phase, and then the bisensory treatment followed by a second washout phase.

Main results and measures  

The primary endpoints were changes in TFI score and tinnitus intensity level from baseline to week 6 and week 12.

Results  

Of 337 individuals screened, 99 (mean [SD] age, 47 [12.7] years; 59 men [60%]; 85 non-Hispanic white race and ethnicity [86%]) were enrolled in the study and randomized to receive treatment group 1 (n = 49) or group 2 (n = 50).

Active treatment, but not control, produced clinically significant reductions in TFI scores at week 6 of phase 1 (ITT population: -12.0 [95% CI, -16.9 to -7.9 ] points; P < 0.001; population PP: -13.2 [95% CI, –16.0 to –10.5] points, p < 0.001).

Decreases in tinnitus loudness level were greater than 6 dB at sensation level (SL; > half as loud) at week 6 for the two-sensory treatment group, with little effect for the treatment-alone control group. hearing at week 6 of phase 1 (ITT population: –5.8 [95% CI –9.5 to –2.2] dB, P = .08; PP population: –7.2 [95% CI %, –11.4 to –3.1] dB; P = 0.03), and up to 11 dB SL at week 12 of phase 2 (ITT population: –10.9 [95% CI, –15, 2 to –6.5] dB; P = 0.001; PP population: –14.1 [95% CI, –18.4 to –9.8] dB, P < 0.001).

The decrease in tinnitus loudness level and TFI scores extended into the washout phase, indicating a prolonged treatment effect.

Conclusions and relevance  

This trial found that precisely timed bisensory treatment using stimuli and timing developed in a validated animal model was effective for adults with somatic tinnitus. Prolonged reduction in tinnitus symptoms may result from the use of a prolonged duration of treatment.

ClinicalTrials.gov Trial Registration Identifier: NCT03621735

Comments

Tinnitus, the ringing, buzzing, or hissing sound of silence, ranges from mildly annoying in some to completely debilitating in others. Up to 15% of adults in the United States have tinnitus, with nearly 40% of patients chronically having the condition and actively seeking relief.

A recent study by researchers at the University of Michigan’s Kresge Hearing Research Institute suggests relief may be possible.

Susan Shore, Ph.D., professor emeritus in the Michigan Medicine Department of Otolaryngology and the UM Departments of Physiology and Biomedical Engineering, led research into how the brain processes bisensory information and how these processes can be harnessed to personalized stimulation to treat tinnitus.

His team’s findings were published in JAMA Network Open .

The study, a randomized, double-blind clinical trial, enrolled 99 people with somatic tinnitus, a form of the condition in which movements such as clenching the jaw or applying pressure to the forehead result in a noticeable change in pitch or loudness. of experienced sounds. Almost 70% of tinnitus sufferers have the somatic form.

According to Shore, candidates with bothersome somatic tinnitus, as well as normal to moderate hearing loss, were eligible to participate.

"After enrollment, participants received a wearable device developed and manufactured by in2being, LLC, for home use," he said. "The devices were programmed to present each participant’s personal tinnitus spectrum, which was combined with electrical stimulation to form a bisensory stimulus, while maintaining blinding of the participants and the study team."

Study participants were randomly assigned to one of two groups. The first group first received a bisensory or active treatment, while the second received a control or sound-only treatment.

For the first six weeks, participants were instructed to use their devices for 30 minutes each day. The next six weeks gave participants a break from daily use, followed by six more weeks of the treatment they did not receive at the start of the study.

Shore notes that each week, participants completed the Tinnitus Functional Index, or TFI, and the Tinnitus Handicap Inventory, or THI, which are questionnaires that measure the impact tinnitus has on people’s lives. Participants were also assessed for tinnitus loudness during this time.

The team found that when participants received the bisensory treatment, they consistently reported better quality of life, lower disability scores, and significant reductions in tinnitus loudness. However, these effects were not observed when receiving sound-only stimulation.

Additionally, more than 60% of participants reported a significant reduction in tinnitus symptoms after six weeks of active treatment, but not control treatment. This is consistent with a previous study by Shore’s team, which showed that the longer participants received active treatment, the greater the reduction in tinnitus symptoms.

"This study paves the way for the use of personalized bisensory stimulation as an effective treatment for tinnitus, providing hope to millions of people who suffer from tinnitus," Shore said.

Auricle Inc., the exclusive licensee of patents related to bisensory stimulation, was launched with the help of Innovation Partnerships, the central hub of research commercialization activity at the University of Michigan. Auricle will work to obtain regulatory clearance and then commercialize Shore’s novel two-sensory tinnitus treatment.