This is a proposal to conduct a multi-center, double-blind, sham-controlled partial cross-over interventional study to test safety and efficacy of our novel tinnitus therapy. The tinnitus field generally accepts that elevated synchronous spontaneous activity in the auditory cortex may account for the tinnitus percept that arises following hearing loss. Following hearing loss that leads to tinnitus, some neurons in the auditory cortex start responding to adjacent frequencies and therefore, a population of neurons becomes over stimulated and starts firing spontaneously and synchronously. This pathological activity is thought to give rise to the tinnitus sensation. Based on these considerations, we developed an approach to reduce the tinnitus percept by redistributing the frequencies along the auditory tonotopic axis, thus reducing the responsiveness of neurons that had too much input. Our therapy pairs selected tone presentations with simultaneous stimulation of the vagus nerve to induce a redistribution of the distorted auditory cortical frequency map observed in tinnitus. Based on our SBIR Phase I results, this approach seemed to alleviate the presumed behavioral and neurophysiological correlates of tinnitus in a rat model of the disease. In our SBIR Phase II studies, we further evaluated and validated the stimulation conditions for reducing the tinnitus precept in our chosen animal model. Based on these positive findings in animals, we evaluated our approach as a therapy for tinnitus in seven humans in a clinical Phase I study in Europe. The preliminary results of that small study suggest that our therapy is safe and can be highly effective in some people. Based on this successful clinical Phase I study, we are seeking to more fully evaluate our therapy in a larger cohort (30 people) using an SBIR Phase II competing renewal award (SBIR Phase IIb). Criteria for Success: We must reduce the magnitude the tinnitus as measured by the minimum masking level. To our knowledge, no masking or pharmacological treatment for tinnitus has reliably reduced this measure. Based on our preliminary findings in humans, we expect that our treatment will reduce the primary measure by 7 dB or more in at least 50% of subjects and the reductions will last for months. A clinically significant MML change is any value greater than 5 dB. Numerous standard subjective measures of tinnitus are also expected to show a reduction or trend toward reduction. No serious adverse events that can be attributed to our therapy should be observed. A successful trial will lead to a clinical Phase III double-blind efficacy study and mechanistic studies. If the Phase III trial is successful, we expect to deploy a commercial device immediately following FDA approval.
Tinnitus is a sensation of a constant ringing in the ears in the absence of external sound. Tinnitus is a debilitating medical condition for millions of Americans. There are no proven treatments for this condition. This is a proposal to develop the first effectiv treatment for alleviating people of this debilitating condition.