Professor Brendan Conlon

Summary

Tinnitus is a phantom auditory perception coded in the brain that can be bothersome or debilitating, affecting 10 to 15% of the population. Currently, there is no clinically recommended drug or device treatment for this major health condition. Animal research has revealed that sound paired with electrical somatosensory stimulation can drive extensive plasticity within the brain for tinnitus treatment. To investigate this bimodal neuromodulation approach in humans, we evaluated a noninvasive device that delivers sound to the ears and electrical stimulation to the tongue in a randomized, double-blinded, exploratory study that enrolled 326 adults with chronic subjective tinnitus. Participants were randomized into three parallel arms with different stimulation settings. Clinical outcomes were evaluated over a 12-week treatment period and a 12-month posttreatment phase. For the primary endpoints, participants achieved a statistically significant reduction in tinnitus symptom severity at the end of treatment based on two commonly used outcome measures, Tinnitus Handicap Inventory (Cohen's d effect size: -0.87 to -0.92 across arms; P < 0.001) and Tinnitus Functional Index (-0.77 to -0.87; P < 0.001). Therapeutic improvements continued for 12 months after treatment for specific bimodal stimulation settings, which had not previously been demonstrated in a large cohort for a tinnitus intervention. The treatment also achieved high compliance and satisfaction rates with no treatment-related serious adverse events. These positive therapeutic and long-term results motivate further clinical trials toward establishing bimodal neuromodulation as a clinically recommended device treatment for tinnitus. Trial undertaken at Clinical Research Facility St James's Hospital.

Funding Agency

Venture Capital / Private Investment

Project Type

Clinical Trial NCT02669069

Summary

More than 10% of the population suffers from tinnitus, which is a phantom auditory condition that is coded within the brain. A new neuromodulation approach has emerged that combines sound with electrical stimulation of somatosensory pathways to treat tinnitus, supported by multiple animal studies demonstrating that bimodal stimulation can elicit extensive neural plasticity within the auditory brain. More recently, in a large-scale clinical trial, bimodal sound and tongue stimulation drove significant reductions in tinnitus symptoms during the first 6-weeks followed by a plateau effect during the second 6-weeks of treatment. The objectives of the large-scale randomized and double-blinded study presented in this paper was to further identify which acoustic or tongue stimuli contribute to therapy and whether changing the parameter settings over time could provide additional improvements in symptoms. The primary endpoints involved within-arm and between-arm comparisons for two treatment arms with different bimodal neuromodulation settings based on two widely used and validated outcome instruments, Tinnitus Handicap Inventory and Tinnitus Functional Index. Both treatment arms exhibited a highly statistically significant reduction in symptoms during the first 6-weeks, which was further reduced during the second 6-weeks of treatment by changing the parameter settings (Cohen's d effect size for full treatment period per arm and outcome measure ranged from -0.7 to -1.4). These therapeutic effects were sustained up to 12 months after the treatment ended. There were no significant differences between arms, suggesting that tongue stimulation paired with pure tones and/or with noise stimuli, as well as different inter-stimulus delays, were equivalently effective in treating tinnitus. Two additional arms, including one arm that presented only acoustic stimuli during the first 6-weeks of treatment, further revealed the importance of both the acoustic and tongue components for reducing tinnitus symptoms. Overall, there were no treatment-related serious adverse events and a high compliance rate (83.8%) with 70.3% of participants indicating that they had benefited from the treatment. The discovery that adjusting stimulus components and parameters over time can drive additional therapeutic effects opens up new opportunities for optimizing stimuli and enhancing clinical outcomes for tinnitus patients with bimodal neuromodulation. Trial undertaken at Clinical Research Facility St James's Hospital.

Funding Agency

Venture Capital / Private Investment

Project Type

Cinical Trial