Treating stress and anxiety in individuals with alcohol use disorder (AUD) using a combination of TRPV-1 channel and C-tactile fiber activation with measurement of oxytocin and cortisol levels

Abstract Alcohol Use Disorder (AUD) affects 29.5 million people in the United States, and about 70% of those seeking AUD treatment suffer a relapse in the first year. Stress and anxiety can trigger a relapse. There are no medications approved for treating these flares and behavioral approaches are limited. Soovu Labs is developing wearable medical device to treat anxiety and stress by stimulation of peripheral C-Tactile (CT) fibers and thermally sensitive TRPV-1 channels. Phase I will determine the “best” stimulation paraments for these targets and then perform a proof of concept study. Phase II will create and test a novel wearable device that stimulates two separate neurological pathways for use in treating symptoms of anxiety and stress in those with AUD. That device will be modeled after our commercial pain relief device, the Soovu Pain Relief Device. CT fibers are found in the skin of most mammals and project to the insular cortex. Stimulation of CT fibers by light touch causes a release of oxytocin and is associated with feelings of comfort and wellbeing. Peripheral TRPV-1 channels are important in pain transmission and modulation of the stress response likely through the central release of oxytocin and are stimulated by heat. In Phase 1 we will test stimulation of TRPV1 channels and CT fibers in human subjects to correlate the lab findings with subjective human responses and test whether stimulation of CT fibers and TRPV-1 channels reduce anxiety and stress in subjects who suffer from AUD. Aim 1 and 2. We will define the optimal parameters for CT fiber stimulation for force, temperature, and body location. We will perform similar testing for peripheral thermal stimulation (TRPV-1) using our commercially available heating pods. Parameters tested will include the optimal body location, number of heating pods (2-4) and temperature of pods. In Aim 3 we will simultaneously apply both CT fiber and thermal stimulation in a proof of concept study. The experimental group will receive active CT fiber and thermal stimulation and the control group non-physiologic placebo stimulation. Subjects with a history of AUD will be randomized into control versus experimental groups and undergo stress using a validated mental calculation stressors. Stress, cravings, and anxiety will be measured using standardized assessments, and we will measure salivary oxytocin and cortisol levels, potentially biomarkers. Phase 2 overview: Phase II will create and test a new wearable medical device that reduces stress and anxiety by direct stimulation of the peripheral nervous system. The new device will be controlled by the user via a phone app with support functions delivered via the app in a manner similar to the current one used by Soovu’s pain relief device. The new device will be the first to offer a rapid onset nondrug intervention to treat stress and anxiety for those with AUD.