Alcohol Use Disorder, Alcohol Withdrawal
Conditions
Keywords
vagus nerve stimulation (VNS), non-invasive intervention
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.
Interventions
510(K) number: K110390 vagus nerve for 5 minutes twice a day for 4 consecutive days
DEVICESham Stimulation
sham stimulation (no electrical current) for 5 minutes twice a day for 4 consecutive days
Sponsors
Northwell Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
Randomized, single-blinded Treatment vs sham
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The primary clinical outcome is the reduction of the alcohol withdrawal symptoms assessed by the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) | 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
| Measure | Time frame | Description |
|---|---|---|
| Assesssment of change of neruroinflammatory reflex by measurement of blood levels of cytokines following VNS treatment for acute alcohol withdrawal | 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. |
Countries
United States
Outcome results
None listed