In Phase I, we demonstrated the feasibility of using VNS stimulation paired with tone presentations to completely reverse the effects of tinnitus in a rat model of the disease.
The Specific Aim of Phase II is to accumulate data for the submission of an IDE application for testing the safety and efficacy of our therapeutic VNS device in humans. Approximately 12 million individuals in the United States have been diagnosed with tinnitus of which ~1 million have severe tinnitus interfering with their daily activities. Although many advances have been made in symptomatic treatments, these treatments are unable to eliminate the tinnitus sensation in most patients. Our therapeutic device will use a PC based software package to allow for computer controlled VNS to be paired with the presentation of tones. This system will be easily deployable as a laptop PC driven rehabilitation therapy device. We have partnered with Texcel (East Longmeadow, MA) to use their StimX VNS stimulation device and software to deliver our therapy in the clinic. The Texcel system is currently in clinical trials for an unrelated indication. While we have proven the feasibility of pairing tone and VNS to reverse tinnitus in rats in Phase I, we must now investigate stimulus parameters more thoroughly in order to develop a rational protocol for humans. VNS parameters have translated well from rats to humans for epilepsy, depression, and learning. It therefore seems reasonable to use a rat model of tinnitus to set the first order parameters for treating tinnitus in humans. Along these same lines, it seems reasonable to use a rat model to evaluate several possible clinical confounds that might occur. In addition, while obtaining FDA approval for testing therapies in humans does not require a mechanistic explanation;experience has shown this to be very useful;we will investigate such a mechanism at a very high level. In parallel to these animal studies, we will be developing the software needed to drive the StimX device at the appropriate parameters for tinnitus therapy. The software is not currently designed to stimulate at our desired parameters. Finally, we will test the software modification and our proposed initial clinical stimulation protocol for efficacy in a rat model of tinnitus. If this final test is successful, we will then assemble and file an IDE for clinical testing. Filing this IDE will conclude a successful Phase II study. We expect to start a clinical trail within 90 days of concluding this Phase II study. If VNS-induced plasticity is effective in treating tinnitus in patients, the technology may also be useful to treat other neurological conditions, including stroke, chronic pain, and epilepsy by pairing each of these conditions with appropriate external cues to retrain pathologically altered neural circuits.
This is a Phase II SBIR application to develop a therapy for tinnitus. Our Phase I studies demonstrated that our overall therapeutic approach can induce lasting and complete reverse of tinnitus using a safe and inexpensive method of vagal nerve stimulation paired with presentation of sounds. Tinnitus is a devastating disease for millions of Americans. Severe forms of tinnitus are debilitating and untreated. This project will move our therapy toward clinical trials to test efficacy in humans.
