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Using Transcutaneous Auricular Vagus Nerve Stimulation to Treat Acute Alcohol Withdrawal

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04159909
Recruitment Status : Not yet recruiting
First Posted : November 12, 2019
Last Update Posted : March 3, 2020
Sponsor:
Information provided by (Responsible Party):
Northwell Health

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Alcohol Withdrawal Alcohol Use Disorder Device: Transcutaneous Nerve Stimulation Device: Sham Stimulation Not Applicable

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, single-blinded Treatment vs sham
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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.


Other Outcome Measures:
  1. 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.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. age 18-65 years (men and women);
  2. primary current diagnosis of DSM-V Alcohol Use Disorder as indicated at admission;
  3. being admitted to inpatient detoxification unit;
  4. no evidence of significant cognitive impairment with a mini mental state examination (MMSE; Folstein et al., 1975) score > 22;
  5. able and willing to give written informed consent and comply with the requirements of the study protocol.

Exclusion Criteria:

  1. current DSM-V substance use disorders (other than tobacco / cannabis/ alcohol);
  2. serious psychiatric illnesses, e.g. psychotic disorders or bipolar disorder
  3. severe medical illnesses, present or history of, e.g. hepatic encephalopathy, delirium
  4. history of significant medical problems associated with drinking including seizures;
  5. pregnancy;
  6. severe intellectual/cognitive deficits due to Korsakoff's syndrome, dementia, head injury, or others
  7. treatment with an anti-cholinergic medication, including over the counter medications,
  8. implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04159909


Contacts
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Contact: Andrew C Chen, MD, PhD 5168371681 achen4@northwell.edu
Contact: Valentin A Pavlov, PhD 5165622316 VPavlov@northwell.edu

Locations
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United States, New York
Feinstein Institutes for Medical Research, Northwell Health
Manhasset, New York, United States, 11030
Contact: Andrew C Chen, MD, PhD    516-837-1681    achen4@northwell.edu   
Contact: Valentin A Pavlov, PhD    5165622316    vpavlov@northwell.edu   
Sponsors and Collaborators
Northwell Health
Investigators
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Principal Investigator: Andrew C Chen, MD, PhD Northwell Health
Publications:
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Responsible Party: Northwell Health
ClinicalTrials.gov Identifier: NCT04159909    
Other Study ID Numbers: 19-0576
First Posted: November 12, 2019    Key Record Dates
Last Update Posted: March 3, 2020
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Northwell Health:
vagus nerve stimulation (VNS), non-invasive intervention
Additional relevant MeSH terms:
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Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders