Opioid Use DisorderNCT04916600
NET Device for Treating Opioid Use Disorder
A study testing NET in people with Opioid Use Disorder, run by Wayne State University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Opioid Use Disorder
- What is being tested?
- NET
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 108 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Nov 2021to Dec 2025
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Isaiah House Treatment Center
Willisburg, Kentucky, 40078
About this study
Official title: 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.
Read the 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.
- Conditions
- Opioid Use Disorder
- Being tested
- NET
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NETDevice
NET is an investigational device that received CE-Mark in April 2009 as a Class IIa active medical device
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: NET |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
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
Measured: 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).
Measured: 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
Measured: Number of adverse events during inpatient device use (which can range across participants from 1 hour to 7 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2021
- Study start24 Nov 2021
- Primary completion7 Jul 2023
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wayne State University
- Sponsor type
- University, hospital or other
- Collaborators
- NET Recovery Corp, Isaiah House
- Responsible party
- Principal investigator, Mark Greenwald, PhD, Wayne State University
- Investigators
- Mark K Greenwald, PhD, Principal investigator, Wayne State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04916600
- Sponsor's protocol ID
- IRB 21-07-3820
- Status last verified
- Sep 2025
- First submitted
- 3 Jun 2021
- Last updated
- 18 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: This is a proprietary device and company-sponsored clinical trial. No IPD will be made available.
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.
PubMed 36303593Greenwald 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.
PubMed 40046990Greenwald 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.
PubMed 41169495
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NET Device as a Non-Pharmacological Alternative to Medication for Opioid Withdrawal Symptom Reduction and Abstinence
- ClinicalTrials.gov ID
- NCT04916600
- Acronym / sponsor ID
- IRB 21-07-3820
- Conditions
- Opioid Use Disorder
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 108 participants (actual)
- Lead sponsor
- Wayne State UniversityUniversity, hospital or other
- Collaborators
- NET Recovery Corp, Isaiah House
- Study start
- 24 Nov 2021 (actual)
- Primary completion
- 7 Jul 2023 (actual)
- Study completion
- Dec 2025 (estimated)
- First posted
- 7 Jun 2021 (actual)
- Results
- Posted 7 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| NET active | Experimental | Device: NETActive, 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. |
| NET sham | Sham comparator | Device: NETSham, 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NETNET is an investigational device that received CE-Mark in April 2009 as a Class IIa active medical device | Device | NET active, NET sham |
Primary outcome
Clinically Meaningful Decrease in Opioid Withdrawal Symptom Severity
Time frame: from baseline to 1-hour of device stimulation
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
3 secondary outcomes
Comparison of Change in Opioid Withdrawal Symptom Severity Between Active and Sham Device Treatment
Time frame: from baseline to 1-hour of device stimulation
Comparison of the Rate of Illicit Opioid Abstinence Without Medications for Treating Opioid Use Disorder
Time frame: 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
Time frame: Number of adverse events during inpatient device use (which can range across participants from 1 hour to 7 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 36303593Greenwald 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.
- Results publication: PubMed 40046990Greenwald 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.
- Derived from this study: PubMed 41169495Greenwald 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.
- Individual participant dataSharing planned: No. This is a proprietary device and company-sponsored clinical trial. No IPD will be made available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark K Greenwald, PhD principal investigator
Wayne State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing NET in people with Opioid Use Disorder, run by Wayne State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 18 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinically Meaningful Decrease in Opioid Withdrawal Symptom Severity (time frame: from baseline to 1-hour of device stimulation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04916600, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2025.