Theranova LLC SBIR Phase II Award, June 2021

Abstract Excessive alcohol consumption is the third leading cause of death in the United States, and approximately 15 million Americans suffer from alcohol use disorder (AUD). AUD also economically expensive, with $249 billion spent annually for costs related to healthcare, lost work productivity, and crime. Despite the high prevalence of AUD and its severe consequences, less than 20% of those with AUD receive any treatment, mainly due to key drawbacks of current treatment options. Guidelines for AUD treatment include pharmacotherapy, behavioral intervention, or both. Meta-analyses consistently demonstrate that first-line AUD medications (naltrexone and acamprosate) are only moderately effective, at best. AUD pharmacotherapies also have common side effects that limit acceptability to patients. Similar to medications, behavioral interventions, such as cognitive behavioral therapy (CBT), provide only small/moderate treatment benefits. In addition, programs often require abstinence, which can be a barrier as many AUD patients prefer non-abstinent goals. Recent preclinical and clinical research has shown that acupuncture of a peripheral nerve pathway can significantly modulate craving-, reward-, and withdrawal-related responses for drugs of abuse. We, thus, hypothesize that peripheral nerve stimulation can be an effective treatment for AUD through its direct effects on craving, reward, and withdrawal. Thus, TheraNova has developed the Empower Neuromodulation System, a portable, easy-to-use transcutaneous electrical nerve stimulation (TENS) device for non-invasive nerve stimulation as a treatment for AUD. The Empower Neuromodulation System consists of a small, wearable Controller and gel electrodes that are temporarily adhered to the skin to stimulate the underlying nerve. Our Phase I clinical study with AUD patients demonstrated that the Empower treatment significantly reduced alcohol consumption (mean reduction = 29%, p=0.026), alcohol craving intensity (mean reduction 21%, p=0.001), and anxiety (mean reduction = 31%, pandlt;0.001) (vs. baseline week measurements) after only two weeks of treatment. While promising, this was a two-week, open-label study, so a longer, sham-controlled pivotal trial is needed to rigorously verify that Empower offers a comprehensive AUD treatment. In Aim 1 of this proposal, we will first update the design of the Empower Neuromodulation System and conduct all bench testing required to support an FDA submission. Then, in Aim 2, we will conduct a multi- site, sham-controlled pivotal clinical trial to evaluate the safety, effectiveness, and acceptability of Empower as a treatment for AUD. The data obtained through this work will support FDA clearance, enabling commercialization of the Empower Neuromodulation System as a comprehensive treatment for AUD.Narrative Approximately 15 million Americans suffer from alcohol use disorder (AUD), but current treatment options have low-to-moderate effectiveness and all suffer from one or more key drawbacks. In this Phase II SBIR, we propose further development of the Empower Neuromodulation System, a non-invasive, home-use neuromodulation treatment for AUD. The data obtained through this work will support FDA clearance, enabling commercialization of the Empower Neuromodulation System as a comprehensive treatment for AUD.