Combined tDCS and Cognitive Training for the Treatment of Opioid Addiction

Evidence suggests that cognitive training can improve cognition in individuals with opioid addiction and may improve treatment outcome.The primary objective of this study is to test whether transcranial direct current stimulation (tDCS) can be used to boost the effectiveness of cognitive training in enhancing cognition in opioid use disorder to improve OUD treatment outcome. The UG3 phase is positioned to be in Phase 1 of the FDA Regulatory Pathway in which we will test for the first time the intervention of tDCS + cognitive training in a population with opioid use disorder (OUD) using an RCT design. The UG3 Aims are to determine if the intervention: (A1) is safe and feasible, (A2) induces circuit-based target engagement in a dose dependent manner, (A3) produces improvement in cognition. We will examine (A4) the relationship between changes in cognition and changes in the circuit-based target. Results from the UG3 will inform design details for the UH3. The UH3 phase will be in Phase 2 of the FDA Regulatory Pathway. The UH3 Aims will expand on UG3 aims by examining the effect of the intervention on (A5) clinical efficacy (decreased opioid use), (A6) durability of target engagement, cognition and clinical efficacy, and (A7) explore moderation effect of individually modeled tDCS electric field. At the end of the UH3 phase, we should be positioned to design either a further Phase 2 or 3 Clinical Trial to support a Premarket Approval application. Our double-blind randomized controlled design controls for participant effort and time by having all participants receive cognitive training with randomization to either active or sham tDCS. In the UG3 phase, 30 participants with OUD will be recruited to study the effect of tDCS dose by contrasting those that received 5 vs 10 treatment sessions of active tDCS. Brain imaging, cognitive and behavioral measures will be conducted three times: at baseline, after 5 sessions, and after 10 sessions. Follow-up cognitive and behavioral measures will be collected 1 and 2 months after intervention. This will allow us to examine target engagement, as well as cognition and behavior effects. UG3 milestones are the demonstration of: safety, feasibility, target engagement, and improvement in cognition. Results from the UG3 will determine the number of treatment sessions.for UH3. In the UH3 phase, 100 participants will be recruited to determine clinical efficacy and durability. Brain imaging, cognitive and behavioral measures will be conducted three times: at baseline, after the intervention, and at 1 month follow-up. This will allow us to examine clinical efficacy (decreased opioid use) and durability of the intervention. Our milestones for UH3 are the demonstration of: clinical efficacy, durability, relationship between target engagement and measures of cognition and drug use behavior (decreased opioid use). Impact. Cognitive impairments and its underlying neural mechanisms affect addiction treatment outcomes. We propose the first study to examine how tDCS- augmented cognitive training affects cognition and its related brain circuitry in opioid use disorder, setting the stage for future large scale clinical trials.