Non-invasive vagal nerve stimulation as novel treatment to improve functionaloutcomes in Veterans with alcohol use disorder

Va San Diego Healthcare System, San Diego CA

Investigators

Abstract

Alcohol use disorder (AUD) is a serious mental health disorder that affects more than 40% of US military Veterans, presenting a major burden to this population and to the VA Healthcare System. Relapse rates of AUD are extremely high; over half of Veterans who complete treatment relapse within 6 months, highlighting the need for improved treatments or different treatment targets. Long-term excessive drinking results in homeostatic dysregulation due to changes in the central and autonomic nervous system, which manifests in psychological and physical distress during abstinence and results in the urge to drink to relieve these symptoms. These symptoms, which can be equated to withdrawal, lead to continued harmful drinking and relapse, and are associated with significant functional impairment and reduced quality of life. Current AUD treatments do not effectively mitigate this homeostatic dysregulation and have risks and side effects as well as other limitations. We propose the vagus nerve, which is the main nerve of the parasympathetic branch of the autonomic nervous system and plays an important role in maintaining and restoring physiological homeostasis, as a novel treatment target for AUD. Noninvasive stimulation of the vagus nerve (nVNS) has been shown to alleviate anxiety, depression, and pain, and to reduce affective and physiological symptoms of opioid withdrawal, which are highly overlapping with AUD. We hypothesize that nVNS can restore homeostasis and reduce withdrawal-related distress and craving, and consequently improve functional outcomes and quality of life in Veterans with AUD. The applicant’s current work (CDA-1) demonstrates that nVNS as a rehabilitative treatment for AUD is feasible and that non-invasive neuromodulation is well accepted by Veterans without any serious adverse effects. In addition, CDA-1 data provides preliminary support that nVNS is effective in reducing withdrawal-related distress, alcohol craving, and improving functional outcomes, and that nVNS can alter neural responses in brain regions subserving perception of physical and psychological distress. The goal of this CDA-2 award is to build on this feasibility data and to assess treatment efficacy and mechanism of action in a larger study sample. The proposed study will include 80 Veterans with current AUD (with at least one functional disability due to alcohol use and current alcohol craving based on DSM-5 criteria), who will be randomized to receive nVNS or sham stimulation prior to performing a well-validated heat pain task designed to assess neural and physiological correlates of distress. Subjects will then self-administer nVNS/sham at home twice a day for 7 days and return for a follow-up visit, during which all study components will be repeated. Behavioral assessments of psychological and physiological distress, craving, and functional outcomes will be administered at baseline and post-treatment, as well as at a 1-month follow-up visit. The proposed work has the potential to lead to an innovative, low-risk treatment option with high promise to significantly improve the care and lives of Veterans as there is a need for non-medication, non-psychotherapy options for AUD. nVNS is a low-risk, cost-effective form of neuromodulation that can be safely self-administered at home (treatment application takes 2 minutes), and thus presents a low burden to the patient. As such, this novel, neuromodulatory AUD treatment could be particularly beneficial for Veterans who do not tolerate pharmacotherapy, and who have access or cognitive limitations or stigma concerns that act as barriers to psychotherapy. The CDA-2 training plan is designed to guide the applicant’s development toward becoming an independent productive clinical researcher within the VA Healthcare System with expertise in neuroscience- based rehabilitation of AUD.