Using Transcutaneous Auricular Vagus Nerve Stimulation to Treat Acute Alcohol Withdrawal
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|ClinicalTrials.gov Identifier: NCT04159909|
Recruitment Status : Not yet recruiting
First Posted : November 12, 2019
Last Update Posted : March 3, 2020
|Condition or disease||Intervention/treatment||Phase|
|Alcohol Withdrawal Alcohol Use Disorder||Device: Transcutaneous Nerve Stimulation Device: Sham Stimulation||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Randomized, single-blinded Treatment vs sham|
|Masking:||Double (Participant, Outcomes Assessor)|
|Official Title:||Using Transcutaneous Auricular Vagus Nerve Stimulation to Treat Acute Alcohol Withdrawal|
|Estimated Study Start Date :||April 15, 2020|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||January 31, 2022|
Experimental: VNS transcutaneous stimulation
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
510(K) number: K110390 vagus nerve for 5 minutes twice a day for 4 consecutive days
Sham Comparator: Sham stimulation
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
sham stimulation (no electrical current) for 5 minutes twice a day for 4 consecutive days
- The primary clinical outcome is the reduction of the alcohol withdrawal symptoms assessed by the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) [ Time Frame: 3 months after completion of pilot study (enrollment) ]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.
- Assesssment of change of neruroinflammatory reflex by measurement of blood levels of cytokines following VNS treatment for acute alcohol withdrawal [ Time Frame: 6 months after completion of pilot study (enrollment) ]The mechanistic endpoints accompanying this protocol will evaluate potential effects of VNS on inflammatory markers and cytokines known to be involved with AUD. 8 ml venous whole blood from participants will be collected on Day 1 before receiving any VNS or sham treatment and on Day 5 after completing all 8 treatments. Serum and plasma from 8cc of whole blood will be collected, stored in aliquots at -20∙C. Serum levels of potential inflammatory markers and markers regulated by the alpha-7nAChR will be determined, including levels of pro-inflammatory cytokines, TNF, HMGB1, IL-6, Il1B, IFNα and IL10 which are known to be elevated in patients with AUD.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04159909
|Contact: Andrew C Chen, MD, PhDfirstname.lastname@example.org|
|Contact: Valentin A Pavlov, PhD||5165622316||VPavlov@northwell.edu|
|Principal Investigator:||Andrew C Chen, MD, PhD||Northwell Health|