Opioid Use Disorder
Conditions
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.
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.
Interventions
DEVICENET
NET is an investigational device that received CE-Mark in April 2009 as a Class IIa active medical device
Sponsors
NET Recovery Corp
Isaiah House
Wayne State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinically Meaningful Decrease in Opioid Withdrawal Symptom Severity | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Change in Opioid Withdrawal Symptom Severity Between Active and Sham Device Treatment | from baseline to 1-hour of device stimulation | 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 |
| 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 | 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). |
| Rate of Adverse Events | Number of adverse events during inpatient device use (which can range across participants from 1 hour to 7 days) | All adverse events including dermal rash, inflammation, or other adverse events from use of the device |
Countries
United States
Participant flow
Recruitment details
A total of 108 participants were enrolled. 53 were enrolled in the active device arm and 55 were enrolled in the sham device arm.
Pre-assignment details
Randomization to active vs. sham conditions was preserved.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 53 |
| 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. | 55 |
| Total | 108 |
Baseline characteristics
| Characteristic | NET Active | Total | NET Sham |
|---|---|---|---|
| Age, Continuous | 34.7 years STANDARD_DEVIATION 7.6 | 34.1 years STANDARD_DEVIATION 8.4 | 33.4 years STANDARD_DEVIATION 9.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 103 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 48 Participants | 97 Participants | 49 Participants |
| Region of Enrollment United States | 53 Participants | 108 Participants | 55 Participants |
| Sex: Female, Male Female | 22 Participants | 44 Participants | 22 Participants |
| Sex: Female, Male Male | 31 Participants | 64 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 55 |
| other Total, other adverse events | 1 / 53 | 0 / 55 |
| serious Total, serious adverse events | 0 / 53 | 0 / 55 |
Outcome results
Primary
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
Time frame: from baseline to 1-hour of device stimulation
Population: All enrolled participants who completed 1 hour of randomly assigned intervention (active or sham)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NET Active | Clinically Meaningful Decrease in Opioid Withdrawal Symptom Severity | 98.1 percentage of participants |
| NET Sham | Clinically Meaningful Decrease in Opioid Withdrawal Symptom Severity | 83.6 percentage of participants |
Secondary
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
Time frame: from baseline to 1-hour of device stimulation
Population: All enrolled participants who completed 1 hour of randomly assigned device utilization (active or sham)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NET Active | Comparison of Change in Opioid Withdrawal Symptom Severity Between Active and Sham Device Treatment | -61.7 percentage change in COWS score | Standard Deviation 4.9 |
| NET Sham | Comparison of Change in Opioid Withdrawal Symptom Severity Between Active and Sham Device Treatment | -45.8 percentage change in COWS score | Standard Deviation 8.9 |
Secondary
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).
Time frame: Overall percentage of zero use-days (no illicit opioids without medications for treating opioid use disorder) during post-discharge weeks 1-12
Population: All participants who (during the inpatient period) received randomly assigned device exposure (active or sham)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NET Active | Comparison of the Rate of Illicit Opioid Abstinence Without Medications for Treating Opioid Use Disorder | 87.0 percentage of participants |
| NET Sham | Comparison of the Rate of Illicit Opioid Abstinence Without Medications for Treating Opioid Use Disorder | 40.0 percentage of participants |
| Sham Device >= 24 Hours | Comparison of the Rate of Illicit Opioid Abstinence Without Medications for Treating Opioid Use Disorder | 52.4 percentage of participants |
| Sham Device <24 Hours Utilization | Comparison of the Rate of Illicit Opioid Abstinence Without Medications for Treating Opioid Use Disorder | 52.9 percentage of participants |
Secondary
Rate of Adverse Events
All adverse events including dermal rash, inflammation, or other adverse events from use of the device
Time frame: Number of adverse events during inpatient device use (which can range across participants from 1 hour to 7 days)
Population: All participants receiving exposure to the randomly assigned intervention (active or sham)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NET Active | Rate of Adverse Events | 1 Participants |
| NET Sham | Rate of Adverse Events | 0 Participants |
Post Hoc
Average Number of Use-days
Average number of days using illicit opioids, illicit psychostimulants, or medications for opioid use disorder (MOUD)
Time frame: Days 1 to 30 post-discharge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NET Active | Average Number of Use-days | 0.5 days | Standard Deviation 1.9 |
| NET Sham | Average Number of Use-days | 3.9 days | Standard Deviation 7.6 |
p-value: 0.032t-test, 2 sided
Post Hoc
Zero Days Use
Percentage of participants with zero days of using illicit opioids, illicit psychostimulants, and medications for treating opioid use disorder (MOUD)
Time frame: Days 1 to 30 post-discharge
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NET Active | Zero Days Use | 87.0 percentage of participants |
| NET Sham | Zero Days Use | 65.0 percentage of participants |
p-value: 0.043Chi-squared