A randomized, sham-controlled, quintuple-blinded trial to evaluate the NET device as an alternative to medication for promoting opioid abstinence

Mark K Greenwald, Samiran Ghosh, Joe R Winston, Mark K Greenwald, Samiran Ghosh, Joe R Winston

Abstract

Background: There is an unmet need for non-medication approaches to illicit opioid discontinuation and relapse prevention. The NET (NeuroElectric Therapy) Device is a non-invasive, battery-operated, portable, re-useable device designed to deliver bilateral transcranial transcutaneous alternating current electrical stimulation, and is intended to treat opioid use disorder (OUD) without medication. The device is a CE-marked Class IIa, non-significant risk, investigational medical device.

Objective: This prospective trial (NRC021) tests the hypothesis that the NET Device provides safe and effective neurostimulation treatment for persons with OUD who express a desire to be opioid abstinent without medications for opioid use disorder (MOUD).

Methods: NRC021 is a randomized, parallel-group, sham-controlled, quintuple-blinded, single-site study. Persons with OUD entering a residential treatment facility for opioid detoxification are assigned to active or sham treatment (n = 50/group). Group assignment is stratified on presence of any current non-opioid substance use disorder and by sex. The biostatistician maintains the blinding so that the study sponsor, principal investigator, research assistants, treatment staff, and participants remain blinded. Following discharge from the inpatient facility, participants are assessed once weekly over 12 weeks for substance use (using timeline followback interview and video assessment of observed oral fluid sample provision and testing). The primary efficacy endpoint is each participant's overall percentage of weekly abstinence from illicit opioid use without use of MOUD. The secondary efficacy endpoint is each participant's percentage of non-opioid drug-free weeks. Safety outcomes are also measured.

Conclusion: NRC021 is designed to assess the efficacy of a novel non-medication treatment for OUD.

Clinical trial registration: ClinicalTrials.gov with the identifier NCT04916600.

Keywords: Craving; Detoxification; Medications; Opioid use disorder; Transcranial electrical stimulation; Withdrawal.

Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MKG consults for Indivior Inc, which makes buprenorphine products. Indivior played no role in this study. SG declares no competing interests. JRW is chief executive officer and co-founder of NET Recovery Corp., which sponsors this study.

© 2022 Published by Elsevier Inc.

Figures

Fig. 1
Fig. 1
Upper panels: NET Device (left), mastoid-region electrode placement (middle), and cumulative distribution function of participants’ device utilization (percentage of sample with device “on”) across hours in two pilot studies conducted in Kentucky and Scotland (right). Lower panels: Time course of device intensity setting (left), and cumulative distribution functions of scores for the Subjective Opioid Withdrawal Scale (SOWS; middle) and craving (right).
Fig. 2
Fig. 2
Study schema Notes: “NET”, NeuroElectric Therapy. “COWS”, Clinical Opiate Withdrawal Scale. “TLFB”, Timeline Followback.
Fig. 3
Fig. 3
Schedule of Activities Notes: “OP”, outpatient. “Wk”, week. “sa”, self-administered. “BP”, blood pressure. “COWS”, Clinical Opiate Withdrawal Scale, “HR”, heart rate. “RR”, respiration rate. “O2”, oxygen saturation.

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