EMPOWER AUD Pivotal Trial

Study Overview
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Brief Summary
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Multi-site, double-blinded, prospective, randomized, sham-controlled study

Detailed Description
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To evaluate the safety and effectiveness of the Empower Neuromodulation System in alcohol use disorder (AUD) patients. The primary safety endpoint will be device-related serious adverse events. The primary effectiveness endpoint will be responder rate at 12 weeks, where a responder is defined as a subject who experiences at least a one level reduction in the WHO risk level for daily alcohol consumption from Baseline to Week 12 as measured via the 28-day Timeline Follow-back (TLFB). Responder rate will be compared between subjects randomized to the active treatment vs. the sham treatment.

Official Title
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Evaluation of the Empower Neuromodulation System for the Treatment of Alcohol Use Disorder

Conditions
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Alcoholism, Alcohol Abuse, Alcohol Use Disorder

Intervention / Treatment
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* Device: Empower Neuromodulation System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A candidate for this study must meet ALL of the following inclusion criteria: Women and men ≥21 years of age Individual has a current diagnosis of alcohol use disorder per DSM-5 via M.I.N.I. assessment by clinician Individual has a desire to reduce or quit alcohol use Based on the 28-day TLFB at enrollment, individual has an average daily alcohol consumption in the WHO risk levels of moderate, high, or very high (men: ≥2.91 drinks/day; women: ≥1.41 drinks/day) Individual has a breath alcohol concentration of 0.02% or less at enrollment Individual has a negative urine pregnancy test at screening (females of childbearing age only) Individual is able to provide informed consent Individual is capable and willing to follow all study-related procedures Exclusion Criteria: A candidate will be excluded from the study if ANY of the following conditions are met: Individual has a current, unstable psychiatric disorder per DSM-5 via M.I.N.I. assessment that is clinically significant enough to preclude study participation per the judgment of the study site PIs Individual has been diagnosed with a neurodegenerative disease, including Parkinson's disease, dementia, and Alzheimer's disease Individual has a current substance use disorder (SUD) diagnosis other than alcohol, nicotine, or cannabis per DSM-5 via M.I.N.I. assessment by clinician Individual requires acute medical detoxification from alcohol per based on a score of 12 or more on the Clinical Institute Withdrawal Assessment Alcohol Scale Revised (CIWA-Ar) Individual is taking or plans to start taking an AUD pharmacotherapy during the study Individual has had a change in AUD pharmacotherapy in the past 4 weeks Individual has initiated or discontinued SUD psychotherapy in the past 4 weeks, has had a change in SUD psychotherapy modality in the past 4 weeks, or expects to initiate, discontinue, or change psychotherapy modality during the study Individual has an active implant and/or an implanted electrical or neurostimulator device (e.g., pacemaker, defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, sacral stimulator, bone growth stimulator, or cochlear implant) Individual is currently using, or has used in the past 3 months, transcutaneous electrical nerve stimulation (TENS) in the upper extremities Individual is currently receiving, or has received in the past 3 months, acupuncture, or acupressure in the upper extremities Individual has an electrically conductive metal object (e.g., jewelry) that cannot be removed and will directly contact the gel electrodes of the Empower Neuromodulation System at either treatment location Individual has an open incision, wound, scar, active infection or otherwise compromised skin at the treatment locations and will directly contact the gel electrodes of the Empower Neuromodulation System at either anatomic location Individual has a history of epilepsy or a seizure disorder Individual has been clinically diagnosed with peripheral nerve damage of the upper limbs or has numbness or tingling in an upper limb at least weekly Individual is female and currently pregnant or breastfeeding, has been pregnant within the past 6 months, intends to become pregnant during participation in the study, or is unwilling to practice birth control during participation in the study Individual will not, for the duration of participation in the study, have a living situation that provides regular access to an electrical outlet for charging the study device and smartphone Individual has used an investigational drug, biologic, or medical device in the past 4 weeks Individual is deemed unsuitable for enrollment in the study by the investigator based on the subject's history or physical examination

Ages Eligible for Study
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Minimum Age: 21 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
Interventional Model Description: Multi-center, double-blinded, prospective, randomized, sham-controlled study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Treatment<br>The Active Treatment will use a functional Stimulator system. | Device: Empower Neuromodulation System<br>* The Empower Neuromodulation System is designed to provide transcutaneous stimulation to the branches of a spinal nerve. The system comprised of three key components: (A) The Stimulator, (B) the Empower smartphone app, and (C) the Gel Patch. The smartphone application is used to coordinate treatment and record participant responses.<br>|
| Sham Comparator: Sham Treatment<br>The Sham Treatment (Placebo) will use a functional Stimulator system, but will provide a treatment in a location that is believed to have no benefit or harm to the subject. | Device: Empower Neuromodulation System<br>* The Empower Neuromodulation System is designed to provide transcutaneous stimulation to the branches of a spinal nerve. The system comprised of three key components: (A) The Stimulator, (B) the Empower smartphone app, and (C) the Gel Patch. The smartphone application is used to coordinate treatment and record participant responses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Safety Endpoint: Frequency of device-related Serious AEs (SAEs) | The primary safety endpoint will be comparing the frequency of device-related Serious AEs (SAEs) between the Active and Sham Treatment groups, where device-related SAEs include probably and possibly device-related serious adverse events | Week 12 | 
| Primary Effectiveness Endpoint: Change in WHO risk level via 28-day TLFB | The primary effectiveness endpoint is the responder rate at Week 12, where a responder is a study subject who experiences ≥1 level reduction in the WHO risk level from Baseline to Week 12 via the 28-day Timeline Follow-back (TLFB), and responder rate is the percentage of participants in a treatment group who are responders | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alcohol Craving Intensity via the Penn Alcohol Craving Survey (PACS) | Change in alcohol craving intensity. The change in alcohol craving intensity as assessed via the Penn Alcohol Craving Survey (PACS) from Baseline to Week 12 will be compared between the Active and Sham Treatment groups. The scale has a range of 0-30 where a higher score indicates more severe cravings. | Week 12 | 
| Change in Heavy Drinking Days (HDD) via 28-day TLFB | Change in heavy drinking days (HDD). The change in HDD as assessed via the 28-day Timeline Follow-Back (TLFB) from Baseline to Week 12 will be compared between the Active and Sham Treatment groups, where a HDD is defined as 5 or more drinks for men and 4 or more drinks for women in one calendar day | Week 12 | 
| Change in Alcohol Related Problems via SIP | Change in alcohol-related problems. The change in alcohol-related problems as assessed via the Short Index of Problems (SIP) from Baseline to Week 12 will be compared between the Active and Sham Treatment groups. The total score has a range of 0-15 where a higher total indicates more problems. | Week 12 | 
| Change in Alcohol Consumption via PEth analysis | Change in phosphatidylethanol (PEth)-based evaluation of alcohol consumption. The change in alcohol consumption as assessed via PEth analysis from Baseline to Week 12 will be compared between the Active and Sham Treatment groups. | Week 12 | 
| Change in Alcohol Craving Intensity via daily self reports | Change in daily alcohol craving intensity. The change in daily alcohol craving intensity as assessed via daily self-reports on the Empower app (100-point Visual Analog Scale (VAS)) from Week 1 to Week 12 will be compared between the Active and Sham Treatment groups. The scale range is 0-100, where the higher rating indicates higher level of alcohol cravings. | Week 12 | 
| Improvement in Clinician Assessment of Illness via CGI | Improvement in clinician assessment of illness. The clinician assessment of improvement in illness as assessed via Clinical Global Impression (CGI) at Week 12 will be compared between the Active and Sham Treatment groups. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcoholism, Alcohol Use Disorder