Alcohol WithdrawalNCT04159909
Using Transcutaneous Auricular Vagus Nerve Stimulation to Treat Acute Alcohol Withdrawal
A study testing Transcutaneous Nerve Stimulation in people with Alcohol Withdrawal and Alcohol Use Disorder, run by Northwell Health at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Alcohol Withdrawal, Alcohol Use Disorder
- What is being tested?
- Transcutaneous Nerve Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2024to 30 Jan 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Feinstein Institutes for Medical Research, Northwell Health
Manhasset, New York, 11030
About this study
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.
Read the 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.
- Conditions
- Alcohol Withdrawal, Alcohol Use Disorder
- Being tested
- Transcutaneous Nerve Stimulation, Sham Stimulation
- Keywords
- vagus nerve stimulation (VNS), non-invasive intervention
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous Nerve StimulationDevice
510(K) number: K110390 vagus nerve for 5 minutes twice a day for 4 consecutive days
Sham StimulationDevice
sham stimulation (no electrical current) for 5 minutes twice a day for 4 consecutive days
| Study group | Role | What they receive |
|---|---|---|
| VNS transcutaneous stimulation | Experimental | 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. Receives: Device: Transcutaneous Nerve Stimulation |
| Sham stimulation | Sham comparator | 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. Receives: Device: Sham Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months after completion of pilot study (enrollment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2019
- Study start31 Jan 2024 (estimated)
- Primary completion30 Sep 2024 (estimated)
- Study completion30 Jan 2025 (estimated)
Why it stopped: Study site, detoxification unit at South Oaks Hospital, was closed/partially open. Northwell addiction has been unable to provide any projected/workable plan(s).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Alcohol WithdrawalStudies of the same condition, open and under way.
- More trials run by Northwell HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, single-blinded Treatment vs sham
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew C Chen, MD, PhD, Principal investigator, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04159909
- Sponsor's protocol ID
- 19-0576
- Status last verified
- Mar 2024
- First submitted
- 5 Nov 2019
- Last updated
- 13 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 29937968Kreuzer 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.
PubMed 22891061Baker 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.
PubMed 28051842Sullivan 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.
PubMed 2597811
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Using Transcutaneous Auricular Vagus Nerve Stimulation to Treat Acute Alcohol Withdrawal
- ClinicalTrials.gov ID
- NCT04159909
- Acronym / sponsor ID
- 19-0576
- Conditions
- Alcohol Withdrawal, Alcohol Use Disorder
- Keywords
- vagus nerve stimulation (VNS), non-invasive intervention
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study site, detoxification unit at South Oaks Hospital, was closed/partially open. Northwell addiction has been unable to provide any projected/workable plan(s).
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Study start
- 31 Jan 2024 (estimated)
- Primary completion
- 30 Sep 2024 (estimated)
- Study completion
- 30 Jan 2025 (estimated)
- First posted
- 12 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, single-blinded Treatment vs sham
| Arm | Type | Receives |
|---|---|---|
| VNS transcutaneous stimulation | Experimental | Device: Transcutaneous Nerve Stimulation5 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. |
| Sham stimulation | Sham comparator | Device: Sham Stimulation5 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcutaneous Nerve Stimulation510(K) number: K110390 vagus nerve for 5 minutes twice a day for 4 consecutive days | Device | VNS transcutaneous stimulation |
| Sham Stimulationsham stimulation (no electrical current) for 5 minutes twice a day for 4 consecutive days | Device | Sham stimulation |
Primary outcome
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.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2024.
- Background: PubMed 29937968Mercante 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.
- Background: PubMed 22891061Kreuzer 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.
- Background: PubMed 28051842Baker 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.
- Background: PubMed 2597811Sullivan 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.
- Individual participant dataSharing planned: No
Related trials for Alcohol Withdrawal
RecruitingPhase 2/3
Effects of Ketone Supplementation on Alcohol Withdrawal and Brain Metabolism in Alcohol Use Disorder
Alcohol Use Disorder, Alcohol Withdrawal
RecruitingPhase 2/3
Cannabidiol as an Adjunct Treatment for Alcohol Withdrawal and Craving
Alcohol Use Disorder (AUD), Withdrawal From Addictive Substance; Detoxification
Not yet recruitingPhase 1/2
Intravenous Acetate as an Adjunctive Treatment for Alcohol Withdrawal in Hospitalized Patients
Alcohol Withdrawal, Alcohol Abstinence
Not yet recruitingPhase 2
Psilocybin-Assisted Psychotherapy for the Treatment of Severe Alcohol Use Disorder
Alcohol Use Disorder
Recruiting
tAN for Substance Use Disorder
Alcohol Use Disorder, Alcohol Abuse
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew C Chen, MD, PhD principal investigator
Northwell Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcutaneous Nerve Stimulation in people with Alcohol Withdrawal and Alcohol Use Disorder, run by Northwell Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 13 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: 3 months after completion of pilot study (enrollment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04159909, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2024.