NET Device for Treating Opioid Use Disorder

NCT04916600 | Active Not Recruiting Results FDA Device

• 1 other identifier: IRB 21-07-3820
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Opioid Use Disorder

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Comparison of Change in Opioid Withdrawal Symptom Severity Between Active and Sham Device Treatment

  from baseline to 1-hour of device stimulation

• Comparison of the Rate of Illicit Opioid Abstinence Without Medications for Treating Opioid Use Disorder

  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

  Number of adverse events during inpatient device use (which can range across participants from 1 hour to 7 days)

Study Arms (2)

NET active

EXPERIMENTAL

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 sham

SHAM COMPARATOR

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

Interventions

NET DEVICE

NET is an investigational device that received CE-Mark in April 2009 as a Class IIa active medical device

NET active; NET sham

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wayne State University: lead
• NET Recovery Corp: collaborator
• Isaiah House: collaborator

Study Sites (1)

Isaiah House Treatment Center

Willisburg, Kentucky, 40078, United States

Location

Related Publications (3)

• 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.

  PMID: 36303593 RESULT

• 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.

  PMID: 40046990 RESULT

• Greenwald MK, Arfken CL, Winston JR. Post-discharge use of opioids, psychostimulants, and treatment medications following residential opioid discontinuation with NET Device monotherapy. Front Psychiatry. 2025 Oct 15;16:1627267. doi: 10.3389/fpsyt.2025.1627267. eCollection 2025.

  PMID: 41169495 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Results Point of Contact

• Title: Dr. Mark Greenwald, Professor
• Organization: Wayne State University School of Medicine

mgreen@med.wayne.edu

3139933965

Study Officials

• Mark K Greenwald, PhD

  Wayne State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sham controls for placebo effects, and is designed to minimize sham recognition by participants, research, and treatment personnel. Active and sham arms will receive identical device care and use instructions, equipment, and attachment locations. Visual cues from the device "heartbeat" indicator (light-emitting diode) indicate the device is working. Sham and active both use the NET device without alteration. Sham uses a lead wire rendered non-conductive beforehand, preventing electrical stimulation. The biostatistician will randomly and uniquely assign a pre-printed Study Device Number (SDN) to each lead wire by overlaying a heat shrink tube, pre-printed with a unique SDN, recording the active and sham assignments. Lead wires are inserted into the device. The biostatistician will keep the data in a secure database and will not be involved in recruitment or study procedures. Unblinding will only occur when necessary for treating an adverse event.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry and Behavioral Neurosciences; and Director, Substance Addiction Research Division

Model Details: 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.

Study Record Dates

• First Submitted: June 3, 2021
• First Posted: June 7, 2021
• Study Start: November 24, 2021
• Primary Completion: July 7, 2023
• Study Completion: December 1, 2025
• Last Updated: September 18, 2025
• Results First Posted: August 7, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)