Clinical trial NCT04159909: Using Transcutaneous Auricular Vagus Nerve Stimulation to Treat Acute Alcohol Withdrawal
Official title: Using Transcutaneous Auricular Vagus Nerve Stimulation to Treat Acute Alcohol Withdrawal
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Alcohol Withdrawal
Alcohol Use Disorder
Keywords: vagus nerve stimulation (VNS), non-invasive intervention
Lead sponsor: Northwell Health
Sponsor class: OTHER
First posted: 2019-11-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, single-blinded Treatment vs sham
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
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)
timeFrame: 3 months after completion of pilot study (enrollment)
Secondary outcomes:
Other outcomes:
measure: Assesssment of change of neruroinflammatory reflex by measurement of blood levels of cytokines following VNS treatment for acute alcohol withdrawal
timeFrame: 6 months after completion of pilot study (enrollment)
Locations:
city: Manhasset
country: United States
facility: Feinstein Institutes for Medical Research, Northwell Health
state: New York
Study officials:
affiliation: Northwell Health
name: Andrew C Chen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.