NET Device for Treating Opioid Use Disorder

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Opioid Use Disorder
• Intervention / Treatment: Device: NET

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Willisburg, Kentucky, United States, 40078
      • Isaiah House Treatment Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form.
2. 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).
3. Stated desire to be opioid abstinent without medications for treating opioid use disorder.
4. Male or female, aged 18-65 years.
5. In good general health as evidenced by medical history.
6. 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).
7. 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.
8. Initiating opioid discontinuation at Isaiah House.
9. Clinical Opiate Withdrawal Scale (COWS) total score is 13 or greater.

Exclusion Criteria:

1. Acute/unstable illness: conditions making it unsafe to participate.
2. Chronic illnesses: primarily seizures and dementing illnesses, including medications for these neurological conditions.
3. Current serious psychiatric disease: psychosis, bipolar disorder.
4. Requiring detoxification from alcohol or benzodiazepines.
5. 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.
6. Current diagnosis other than opioid use disorder requiring chronic opioid treatment.
7. Presence of a cardiac pacemaker.
8. 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.
9. Receiving extended-release buprenorphine (Sublocade) within 300 days of enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NET active; 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; NET is an investigational device that received CE-Mark in April 2009 as a Class IIa active medical device
Sham Comparator: NET sham; 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; NET is an investigational device that received CE-Mark in April 2009 as a Class IIa active medical device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically Meaningful Decrease in Opioid Withdrawal Symptom Severity	percentage of participants with 15% or greater reduction (from baseline to 1 hour device utilization) 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 Change in Opioid Withdrawal Symptom Severity Between Active and Sham Device Treatment	Difference in percentage change 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 the Rate of Illicit Opioid Abstinence Without Medications for Treating Opioid Use Disorder	Percentage of participants with no illicit opioid use without use of medications for treating opioid use disorder (based on weekly post-discharge timeline followback interview). This outcome definition is a conjunction (i.e. required combination) of a participant not using any illicit opioid AND not using any medication for treating opioid use disorder at each assessment time point. This is consistent with the intent of the study to examine the efficacy of the device as a monotherapy (without relying on medications).	Overall percentage of zero use-days (no illicit opioids without medications for treating opioid use disorder) during post-discharge weeks 1-12
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)

Collaborators and Investigators

• Sponsor: Wayne State University
• Collaborators: NET Recovery Corp; Isaiah House
• Investigators: Principal Investigator: Mark K Greenwald, PhD, Wayne State University

Publications and helpful links

General Publications

• Greenwald MK, Ghosh S, Winston JR. A randomized, sham-controlled, quintuple-blinded trial to evaluate the NET device as an alternative to medication for promoting opioid abstinence. Contemp Clin Trials Commun. 2022 Oct 18;30:101018. doi: 10.1016/j.conctc.2022.101018. eCollection 2022 Dec.
• Greenwald MK, Arfken CL, Winston JR. A randomized, sham-controlled clinical trial to evaluate the NET Device for reducing withdrawal symptom severity during opioid discontinuation. Front Psychiatry. 2025 Feb 19;16:1510428. doi: 10.3389/fpsyt.2025.1510428. eCollection 2025.

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2021
• Primary Completion (Actual): July 7, 2023
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: June 3, 2021
• First Submitted That Met QC Criteria: June 3, 2021
• First Posted (Actual): June 7, 2021

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders
• Other Study ID Numbers: IRB 21-07-3820

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is a proprietary device and company-sponsored clinical trial. No IPD will be made available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No