Search
Close this search box.

Using Transcutaneous Auricular Vagus Nerve Stimulation to Treat Acute Alcohol Withdrawal

Studies

Study First Submitted Date 2019-11-05
Study First Posted Date 2019-11-12
Last Update Posted Date 2023-04-12
Start Month Year January 31, 2024
Primary Completion Month Year September 30, 2024
Verification Month Year April 2023
Verification Date 2023-04-30
Last Update Posted Date 2023-04-12

Detailed Descriptions

Sequence: 20688587
Description 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.

Facilities

Sequence: 199692280
Name Feinstein Institutes for Medical Research, Northwell Health
City Manhasset
State New York
Zip 11030
Country United States

Facility Contacts

Sequence: 28067245 Sequence: 28067246
Facility Id 199692280 Facility Id 199692280
Contact Type primary Contact Type backup
Name Andrew C Chen, MD, PhD Name Valentin A Pavlov, PhD
Email achen4@northwell.edu Email vpavlov@northwell.edu
Phone 516-837-1681 Phone 5165622316

Conditions

Sequence: 52082952 Sequence: 52082953
Name Alcohol Withdrawal Name Alcohol Use Disorder
Downcase Name alcohol withdrawal Downcase Name alcohol use disorder

Id Information

Sequence: 40088318
Id Source org_study_id
Id Value 19-0576

Countries

Sequence: 42488044
Name United States
Removed False

Design Groups

Sequence: 55496914 Sequence: 55496915
Group Type Experimental Group Type Sham Comparator
Title VNS transcutaneous stimulation Title Sham stimulation
Description 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.

Description 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.

Interventions

Sequence: 52396123 Sequence: 52396124
Intervention Type Device Intervention Type Device
Name Transcutaneous Nerve Stimulation Name Sham Stimulation
Description 510(K) number: K110390 vagus nerve for 5 minutes twice a day for 4 consecutive days Description sham stimulation (no electrical current) for 5 minutes twice a day for 4 consecutive days

Keywords

Sequence: 79723013
Name vagus nerve stimulation (VNS), non-invasive intervention
Downcase Name vagus nerve stimulation (vns), non-invasive intervention

Design Outcomes

Sequence: 177079062 Sequence: 177079063
Outcome Type primary Outcome Type other
Measure The primary clinical outcome is the reduction of the alcohol withdrawal symptoms assessed by the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) Measure Assesssment of change of neruroinflammatory reflex by measurement of blood levels of cytokines following VNS treatment for acute alcohol withdrawal
Time Frame 3 months after completion of pilot study (enrollment) Time Frame 6 months after completion of pilot study (enrollment)
Description 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. Description 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.

Browse Conditions

Sequence: 193136040 Sequence: 193136041 Sequence: 193136042 Sequence: 193136043 Sequence: 193136044
Mesh Term Alcoholism Mesh Term Alcohol-Related Disorders Mesh Term Substance-Related Disorders Mesh Term Chemically-Induced Disorders Mesh Term Mental Disorders
Downcase Mesh Term alcoholism Downcase Mesh Term alcohol-related disorders Downcase Mesh Term substance-related disorders Downcase Mesh Term chemically-induced disorders Downcase Mesh Term mental disorders
Mesh Type mesh-list Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor

Sponsors

Sequence: 48237606
Agency Class OTHER
Lead Or Collaborator lead
Name Northwell Health

Overall Officials

Sequence: 29233798
Role Principal Investigator
Name Andrew C Chen, MD, PhD
Affiliation Northwell Health

Central Contacts

Sequence: 11990499 Sequence: 11990500
Contact Type primary Contact Type backup
Name Andrew C Chen, MD, PhD Name Valentin A Pavlov, PhD
Phone 5168371681 Phone 5165622316
Email achen4@northwell.edu Email VPavlov@northwell.edu
Role Contact Role Contact

Design Group Interventions

Sequence: 68032062 Sequence: 68032063
Design Group Id 55496914 Design Group Id 55496915
Intervention Id 52396123 Intervention Id 52396124

Eligibilities

Sequence: 30714176
Gender All
Minimum Age 18 Years
Maximum Age 65 Years
Healthy Volunteers No
Criteria 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.

Adult True
Child False
Older Adult True

Calculated Values

Sequence: 253946022
Number Of Facilities 1
Registered In Calendar Year 2019
Were Results Reported False
Has Us Facility True
Has Single Facility True
Minimum Age Num 18
Maximum Age Num 65
Minimum Age Unit Years
Maximum Age Unit Years
Number Of Primary Outcomes To Measure 1
Number Of Other Outcomes To Measure 1

Designs

Sequence: 30460744
Allocation Randomized
Intervention Model Parallel Assignment
Observational Model
Primary Purpose Treatment
Time Perspective
Masking Double
Intervention Model Description Randomized, single-blinded Treatment vs sham
Subject Masked True
Outcomes Assessor Masked True

Responsible Parties

Sequence: 28827205
Responsible Party Type Sponsor

Study References

Sequence: 51979225 Sequence: 51979226 Sequence: 51979227 Sequence: 51979228
Pmid 29937968 Pmid 22891061 Pmid 28051842 Pmid 2597811
Reference Type background Reference Type background Reference Type background Reference Type background
Citation Mercante B, Ginatempo F, Manca A, Melis F, Enrico P, Deriu F. Anatomo-Physiologic Basis for Auricular Stimulation. Med Acupunct. 2018 Jun 1;30(3):141-150. doi: 10.1089/acu.2017.1254. Citation Kreuzer PM, Landgrebe M, Husser O, Resch M, Schecklmann M, Geisreiter F, Poeppl TB, Prasser SJ, Hajak G, Langguth B. Transcutaneous vagus nerve stimulation: retrospective assessment of cardiac safety in a pilot study. Front Psychiatry. 2012 Aug 7;3:70. doi: 10.3389/fpsyt.2012.00070. eCollection 2012. Citation Baker TE, Chang G. The use of auricular acupuncture in opioid use disorder: A systematic literature review. Am J Addict. 2016 Dec;25(8):592-602. doi: 10.1111/ajad.12453. Epub 2016 Nov 2. Citation Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict. 1989 Nov;84(11):1353-7. doi: 10.1111/j.1360-0443.1989.tb00737.x.