Using Transcutaneous Auricular Vagus Nerve Stimulation to Treat Acute Alcohol Withdrawal

Alcohol Use Disorder Clinical Trial

Official title:

Using Transcutaneous Auricular Vagus Nerve Stimulation to Treat Acute Alcohol Withdrawal

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04159909
• Other study ID #: 19-0576
• Status: Withdrawn
• Phase: N/A
• Start date: January 31, 2024
• Est. completion date: January 30, 2025

Study information

• Verified date: March 2024
• Source: Northwell Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 30, 2025
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alcohol Use Disorder
• Alcohol Withdrawal
• Alcoholism

Intervention

Device:
• Transcutaneous Nerve Stimulation
510(K) number: K110390 vagus nerve for 5 minutes twice a day for 4 consecutive days
• Sham Stimulation
sham stimulation (no electrical current) for 5 minutes twice a day for 4 consecutive days

Locations

Country	Name	City	State
United States	Feinstein Institutes for Medical Research, Northwell Health	Manhasset	New York

Sponsors (1)

Lead Sponsor	Collaborator
Northwell Health

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assesssment of change of neruroinflammatory reflex by measurement of blood levels of cytokines following VNS treatment for acute alcohol withdrawal	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, IFNa and IL10 which are known to be elevated in patients with AUD.	6 months after completion of pilot study (enrollment)
Primary	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)