Using Transcutaneous Auricular Vagus Nerve Stimulation to Treat Acute Alcohol Withdrawal

Study Overview
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Brief Summary
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The purpose of this study is to see if stimulation of the vagus nerve via a non-invasive device placed behind external ear can reduce physical and psychological discomfort during acute alcohol withdrawal in patients with alcohol use disorder when people just stop drinking alcohol and in detoxification stage.

Detailed Description
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The management of acute alcohol withdrawal is a clinical challenge, in part because there are limited medications available for the condition and the majority of the medications are controlled substances, which may cause significant adverse effects and can be potentially addictive. The rationale for using transcutaneous auricular VNS (taVNS) on a specific target area of the ear is based on anatomical studies suggesting that this area is the only place on the human body surface where there is afferent vagus nerve distribution (Mercante et al., 2018). Therefore, direct stimulation of the afferent nerve fibers on the ear can produce an effect similar to that by implanted device-generated VNS yet without the need of surgical intervention. Although taVNS has not been tested for treatment of AUD, it interestingly appears to be very similar to auricular acupuncture that has been widely used for AUD. However, acupuncture needs to be administered by medical providers who have undergone long trainings and own special licensure, which is usually unavailable in acute detoxification units where patients receive treatment for acute alcohol withdrawal. The pilot study will enroll 70 evaluable subjects who are in inpatient detoxification unit randomized to receive single-blind treatment with vagus nerve stimulation or sham stimulation (1:1, VNS: sham). Evaluable subjects are those who complete stimulations (VNS) or sham 5 minutes twice a day for 4 days.

Official Title
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Using Transcutaneous Auricular Vagus Nerve Stimulation to Treat Acute Alcohol Withdrawal

Conditions
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Alcohol Withdrawal, Alcohol Use Disorder

Intervention / Treatment
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* Device: Transcutaneous Nerve Stimulation
* Device: Sham Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-65 years (men and women); primary current diagnosis of DSM-V Alcohol Use Disorder as indicated at admission; being admitted to inpatient detoxification unit; no evidence of significant cognitive impairment with a mini mental state examination (MMSE; Folstein et al., 1975) score > 22; able and willing to give written informed consent and comply with the requirements of the study protocol. Exclusion Criteria: current DSM-V substance use disorders (other than tobacco / cannabis/ alcohol); serious psychiatric illnesses, e.g. psychotic disorders or bipolar disorder severe medical illnesses, present or history of, e.g. hepatic encephalopathy, delirium history of significant medical problems associated with drinking including seizures; pregnancy; severe intellectual/cognitive deficits due to Korsakoff's syndrome, dementia, head injury, or others treatment with an anti-cholinergic medication, including over the counter medications, implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, single-blinded Treatment vs sham
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VNS transcutaneous stimulation<br>5 minutes of stimulation (VNS) twice a day for 4 days. Patients will receive transcutaneous stimulation (30 Hz, 300 msec.) on the auricular branch of the vagus nerve 5 minutes twice a day for 4 days. Due to the theoretical risk that right vagus nerve stimulation could affect the heart, and to ensure consistency of the intervention, all subjects randomized to receive transcutaneous vagus nerve stimulation will receive stimulation of the auricular branch of the left vagus nerve. The subject will be blinded to their treatment arm. The device to be used will include a handheld electrical pulse generator and a pair of electrodes to be placed at the ear for stimulation. The specific target at the ear will be the auricular branch of the vagus nerve, which innervates the skin of a specific ear area termed Cymba Concha. Electrodes will be placed on this area to provide stimulation to the auricular branch of the afferent vagus nerve. | Device: Transcutaneous Nerve Stimulation<br>* 510(K) number: K110390 vagus nerve for 5 minutes twice a day for 4 consecutive days<br>|
| Sham Comparator: Sham stimulation<br>5 minutes of sham stimulation (no electrical stimulation) twice a day for 4 days Patients will receive sham stimulation on the auricular branch of the vagus nerve 5 minutes twice a day for 4 days. The subject will be blinded to their treatment arm. The specific target at the ear will be the auricular branch of the vagus nerve, which innervates the skin of a specific ear area termed Cymba Concha. Electrodes will be placed on this area to provide sham stimulation (no electrical current) to the auricular branch of the afferent vagus nerve. | Device: Sham Stimulation<br>* sham stimulation (no electrical current) for 5 minutes twice a day for 4 consecutive days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary clinical outcome is the reduction of the alcohol withdrawal symptoms assessed by the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) | The primary clinical endpoint is the alcohol withdrawal symptoms assessed by the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) (Sullivan, Sykora, Schneiderman, Naranjo, & Sellers, 1989) as well as the amount and frequency of as needed comfort medications (benzodiazepines, e.g., Chlordiaxepoxide, Lorazepam) used from day 1 to day 4 by the participants in acute detoxification inpatient unit treated with VNS compared to subjects receiving sham stimulation. | 3 months after completion of pilot study (enrollment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vagus nerve stimulation (VNS), non-invasive intervention