NET Device for Treating Opioid Use Disorder

Study Overview
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Brief Summary
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This prospective, randomized, double-blind, parallel-group, sham-controlled, superiority study will evaluate the effectiveness of the NET Device in treating persons with Opioid Use Disorder (OUD) without use of Medications for OUD (MOUD) for persons who have expressed a desire to be opioid abstinent without use of MOUD.

Detailed Description
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The primary study objective is to determine whether use of the active NET Device produces a clinically meaningful decrease in opioid withdrawal symptom severity from baseline to 1-hour in persons with OUD experiencing moderate or greater symptoms of opioid withdrawal. The NET Device is an investigational Non-Significant Risk device that delivers alternating current via surface electrodes placed transcranially on the mastoid regions. All participants will be screened and undergo evaluation at Isaiah House, a treatment center located in Willisburg, KY. Individual participant treatment (duration of the active/sham device use) is 1 hour and extendable by participant choice, but not to exceed 7 days, delivered at the inpatient facility (typically 28 days duration), with weekly follow-up assessments (efficacy and safety endpoints) following discharge (by video) for a 12-week outpatient study period. Total elapsed time will typically be 16 weeks. The primary study endpoint is a clinically meaningful decline in COWS total score (defined as a ≥15% reduction) from baseline to 1-hour after start of active NET stimulation. The first secondary endpoint is a comparison of the decrease in COWS total scores from baseline to 1-hour after start of intervention for active vs sham. The second secondary efficacy endpoint is a comparison of the percentage of weeks of abstinence from illicit opioid use without the use of MOUD for active vs sham over 12 outpatient weeks following discharge from residential care. The secondary safety endpoint is the prevalence of all adverse events (AEs) and serious adverse events (SAEs) assessed from day 1 baseline to the end of study, and adverse device effects (ADEs), serious adverse device effects (SADEs), unanticipated adverse device effects (UADEs), and device deficiencies assessed from day 1 baseline to end of day 7.

Official Title
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NET Device as a Non-Pharmacological Alternative to Medication for Opioid Withdrawal Symptom Reduction and Abstinence

Conditions
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Opioid Use Disorder

Intervention / Treatment
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* Device: NET


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated informed consent form. Stated willingness to comply with all study procedures and availability for the duration of the study (including inpatient stay and participation in video assessments and remote drug screens for the duration of the 12-week outpatient study period). Stated desire to be opioid abstinent without medications for treating opioid use disorder. Male or female, aged 18-65 years. In good general health as evidenced by medical history. Meet Diagnostic and Statistical Manual (DSM)-5 criteria for opioid use disorder (any severity level) alone or comorbid with stable medical diseases (except for certain medications below). For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method for the duration of the study. Initiating opioid discontinuation at Isaiah House. Clinical Opiate Withdrawal Scale (COWS) total score is 13 or greater. Exclusion Criteria: Acute/unstable illness: conditions making it unsafe to participate. Chronic illnesses: primarily seizures and dementing illnesses, including medications for these neurological conditions. Current serious psychiatric disease: psychosis, bipolar disorder. Requiring detoxification from alcohol or benzodiazepines. Current use of anxiolytics, hypnotics (prescription and over the counter), antidepressants, anticonvulsants, sedating histamine-1 receptor subtype antihistamines (non-sedating second generation histamine-4 receptor subtype antihistamines are allowed), prescription and over the counter stimulants. Current diagnosis other than opioid use disorder requiring chronic opioid treatment. Presence of a cardiac pacemaker. Pregnancy or lactation. Females who do not agree to sexual abstinence or are heterosexually active and not using (self-report) medically approved birth control measures (sterilization, tubal ligation, oral/depot contraceptives, abstinence, intrauterine device, barrier method such as condom/foam, or a cervical cap combined with a spermicide), are not eligible. Receiving extended-release buprenorphine (Sublocade) within 300 days of enrollment.

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
Interventional Model Description: This study is prospective, randomized, double-blind, parallel-group, sham-controlled and superiority in design. Study enrollees will be assigned in equal proportions (1:1) to one of two groups: active or sham treatment. Group assignment will be stratified by sex. The biostatistician will perform stratified randomization to maintain balance between active and sham groups. The biostatistician will maintain the blinding so that the study sponsor, PI, study monitor, research assistants, treatment staff, and the participants remain blinded. No interim analysis is planned.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NET active<br>Active, non-invasive, alternating current transcutaneous stimulation through electrodes placed transcranially on the mastoid regions. Treatment is self-administered, with participant control of device output level and duration according to perceived benefit. Minimum treatment duration is one-hour, with self-administered extension not to exceed 7 days. | Device: NET<br>* NET is an investigational device that received CE-Mark in April 2009 as a Class IIa active medical device<br>|
| Sham Comparator: NET sham<br>Sham, non-invasive, stimulation through electrodes placed transcranially on the mastoid regions. Treatment is self-administered, with participant control of device output level and duration according to perceived benefit. Minimum treatment duration is one-hour, with self-administered extension not to exceed 7 days. | Device: NET<br>* NET is an investigational device that received CE-Mark in April 2009 as a Class IIa active medical device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically meaningful decrease in opioid withdrawal symptom severity | 15% or greater reduction in total score on the Clinical Opiate Withdrawal Scale (COWS); scores range from 0 to 48, with higher scores indicating more severe withdrawal | from baseline to 1-hour of device stimulation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of decrease in opioid withdrawal symptom severity between active and sham device treatment | Difference in the magnitude of reduction in total score on the Clinical Opiate Withdrawal Scale (COWS) between active and sham groups; scores range from 0 to 48, with higher scores indicating more severe withdrawal | from baseline to 1-hour of device stimulation | 
| Comparison of illicit opioid abstinence and no medications for treating opioid use disorder | Difference between active and sham groups in the number of outpatient follow-up weeks with no illicit opioid use and no use of medications for treating opioid use disorder (based on weekly timeline followback interview and oral fluid drug tests) | Overall weekly number across 12 outpatient weeks | 
| Rate of adverse events | All adverse events including dermal rash, inflammation, or other adverse events from use of the device | Number of adverse events during inpatient device use (which can range across participants from 1 hour to 7 days) |