A clinical trial has found that a novel device combining sound and tongue stimulation can reduce tinnitus symptoms, leading to its de novo approval as the first tinnitus treatment of its kind by the U.S. Food and Drug Administration.

The study, published in Nature Communications, found that 12 weeks of treatment with the device, known as Lenire, resulted in clinically significant improvements for many participants with moderate-to-severe tinnitus. Adding tongue stimulation to sound therapy drove greater benefits than sound alone.

Study Design and Methods

The TENT-A3 study enrolled 112 participants across three clinical sites who had chronic tinnitus for 3 to 10 years and a score of ≥38 on the Tinnitus Handicap Inventory (THI), indicating moderate to catastrophic severity. In the first stage, participants received 6 weeks of sound-only stimulation; in the second 6-week stage, electrical tongue stimulation was added. The primary endpoint compared the responder rate (≥7-point THI improvement) between the stages.

Key inclusion criteria included age ≥18 years, a maximum hearing loss of 40 dB HL for 250 Hz to 1 kHz or 80 dB HL for 2 to 8 kHz unilaterally or bilaterally, and the ability to participate for the full 12-week study. Major exclusion criteria included objective/pulsatile tinnitus, Meniere's disease, severe cognitive impairment, and recent tinnitus treatments.

Participants used the Lenire device for 30 to 60 minutes per day. It delivered sound via headphones and electrical stimulation via a 32-site tongue array. Stimulation was configured for each patient's hearing and comfort levels. Safety and compliance were closely monitored.

The study used the THI score—a validated 25-item questionnaire scored from 0 to 100, with higher scores indicating greater tinnitus impact—as the primary outcome measure. The Tinnitus Functional Index (TFI) was a secondary measure. The Health Utilities Index Mark III (HUI3) quality-of-life questionnaire was also administered. Adverse events (AEs) were categorized by ISO 14155:2020 standards.

Of the 112 enrollees, 77 (68.8%) were male. Mean age was 48.9 years (standard deviation [SD] = 12.6 years) and mean tinnitus duration was 4.3 years (SD = 3.1 years). At screening, mean THI score was 50.1 (SD = 11.3), falling in the moderate range, and mean hearing loss was 17.7 dB HL (SD = 10.5).

Results

For participants with moderate-to-severe tinnitus at the start of bimodal stimulation (THI ≥38), 58.6% (95% confidence interval [CI] = 43.5%–73.6%) responded to the combined treatment compared to 43.2% (95% CI = 29.7%–57.8%) for sound-only treatment (P = .022). Across the full cohort, 79.4% of participants responded over the total 12 weeks.

Across the full cohort, the Stage 2 responder rate based on THI was 43.3% (95% CI = 33.9%–52.7%) compared to 63.3% (95% CI = 54.3%–72.2%) in Stage 1. However, the 43.3% Stage 2 response rate represents additional improvement after initial benefits from sound-only treatment. Similar response patterns were seen for males and females.

Based on TFI, where response was defined as a ≥13-point improvement, Stage 2 response was greater than Stage 1 for the THI ≥38 group (45.5%; 95% CI = 31.7%–59.9% vs. 29.6%; 95% CI = 18.2%-44.2%; P = .010).

There were no treatment-related serious adverse events reported in the trial, and 96.8% of device-related adverse events were mild. The most common was transient tinnitus increase, seen more during sound-only treatment. Compliance was 82.4% and satisfaction was high, with 62.9% of participants reporting benefit and 88.6% saying they would recommend the treatment.

Device usage averaged 52.6 min/day for compliant participants in Stage 2. All 62 device-related AEs resolved except 1 mild case lost to follow-up. There were 18 device-related AEs in Stage 2, all mild, compared to 44 in Stage 1 (42 mild and 2 moderate). Increased tinnitus occurred in 12 cases in Stage 2 vs. 40 in Stage 1, suggesting relation to sound stimulation and/or starting treatment.

The HUI3 showed minimal changes, likely due to participants starting with generally good health aside from tinnitus and a "ceiling effect" on the hearing-related component. Notably, 64.9% of participants not responding to sound-only stimulation did respond to added bimodal stimulation, supporting its utility for patients not benefiting from standalone acoustic therapies.

Real-world evidence collected in 204 patients further supported the findings in the moderate-to-severe population.

The study outcomes, safety data, and alignment with real-world experience provide evidence for this bimodal neuromodulation approach. Lenire's U.S. Food and Drug Administration de novo grant establishes a new device category for tinnitus treatment.

Study authors declared that they have no competing interests, except one, who is a consultant with financial interests for Neuromod Devices.