Transcutaneous Auricular Neurostimulation (tAN) for Symptoms of Opioid Withdrawal

Study Overview
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Brief Summary
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Clinical performance data for transcutaneous auricular neurostimulation (tAN) as a method to aid in the reduction of symptoms associated with opioid withdrawal in order to support clinical substantial equivalence to a predicate device.

Detailed Description
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Prior evidence has demonstrated that non-invasive neurostimulation can modulate specific brains regions associated with opioid use disorder and reduce opioid withdrawal symptoms. This is a double blind, randomized, controlled, multi-center study in which subjects will be randomized in a 1:1 ratio to one of two groups: 1) active transcutaneous auricular neurostimulation (tAN) or 2) delayed-active tAN to determine reduction of symptoms related to opioid withdrawal. Subjects in the active tAN group will receive tAN immediately whereas those in the delayed-active tAN will have their therapy turned on after a 30 minute delay (inactive period). All subjects will be informed of their group assignment at the conclusion of the randomized, double blind period (following initial 30 minutes of active or inactive therapy) and all will continue to receive active tAN throughout the five-day study. Each clinical site will have pre-determined and qualified clinical opiate withdrawal scale (COWS) accessor(s) that will be blind to the subjects group designation during the randomized, double blind period and will not be informed that all subjects receive active therapy throughout the remainder of the study. This will ensure a non-biased assessment of the COWS score and maintain single blinding throughout the duration of the study.

Official Title
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Delivering Transcutaneous Auricular Neurostimulation (tAN) to Improve Symptoms Associated With Opioid Withdrawal

Conditions
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Opioid-use Disorder, Opioid Withdrawal

Intervention / Treatment
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* Device: transcutaneous auricular neurostimulation (tAN)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current opioid dependence; prescriptive or non-prescriptive COWS score is ≥ 13 or in the opinion of the investigator the subject is in moderate to severe withdrawal 18-65 years of age English Proficiency Participants must be able to provide informed con-sent and function at an intellectual level sufficient for study requirements Exclusion Criteria: Current evidence of an uncontrolled and/or clinically significant medical condition History of seizures or epilepsy History of neurological diseases or traumatic brain injury Participants using long-acting opioids such as methadone or buprenorphine for a period of five or more consecutive days prior to enrollment Recent suicide attempt leading to current hospital admission or continued expressed suicidal ideation Presence of devices, e.g. pace-makers, cochlear prosthesis, neuro-stimulators Abnormal ear anatomy or ear infection present Women of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study Females who are pregnant or lactating Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: delayed-active tAN<br> | Device: transcutaneous auricular neurostimulation (tAN)<br>* Phoenix tAN system<br>|
| Experimental: active tAN<br> | Device: transcutaneous auricular neurostimulation (tAN)<br>* Phoenix tAN system<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical opiate withdrawal scale (COWS) score | Mean percent change in clinical opiate withdrawal scale (COWS) score from baseline to 60 minutes after start of active tAN therapy. The COWS is an 11-item scale with a score range between 0 and 48. Total score is the sum of all the items and a higher score indicates more severe withdrawal symptoms. Scores between 5 and 12 indicate mild withdrawal, scores between 13 and 24 indicate moderate withdrawal, scores between 25 and 36 indicate moderately severe withdrawal and scores greater than 36 indicate severe withdrawal. A COWS score reduction of 15% or greater for a given individual is considered clinically significant. | 60 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical opiate withdrawal scale (COWS) score | Comparison of mean percent change in COWS score in delayed active tAN versus active tAN groups at 30 minutes | 30 minutes | 
| Clinical opiate withdrawal scale (COWS) responder rate | Comparison of the proportion of participants with a clinically significant reduction in COWS score (defined as a 15% or greater reduction) in delayed-active tAN versus active tAN groups at 30 minutes | 30 minutes | 
| Clinical opiate withdrawal scale (COWS) score | Mean percent change in COWS score from baseline to 30 minutes after start of active tAN therapy | 30 minutes | 
| Clinical opiate withdrawal scale (COWS) score | Mean percent change in COWS score from baseline to 120 minutes after start of active tAN therapy | 120 minutes | 
| Clinical opiate withdrawal scale (COWS) score | Mean percent change in COWS score from baseline to Days 2 through 5 after start of active tAN therapy | Days 2-5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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auricular neurostimulation, vagus nerve stimulation, transcutaneous, withdrawal symptoms