tDCS to Decrease Opioid Relapse

In the current proposal, the investigators will measure behavioral and brain responses following transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex (DLPFC) (anode on right DLPFC, cathode on the left DLPFC) delivered during cognitive control network (CCN) priming. Participants with opioid dependence, in the first month of prescribed buprenorphine or methadone, will be assessed twice using functional magnetic resonance imaging (FMRI) and electroencephalographic (EEG), once prior to tDCS+CCN priming and again at the completion of 5 sessions of tDCS+CCN priming (one week later). Task-based and resting state functional connectivity will be used to examine networks associated with craving (CR) and cognitive control. In Phase 1, FMRI and EEG will provide validation of expected changes in these networks following tDCS stimulation of the DLPFC. In phase 2, the investigators will perform a larger randomized clinical trial (RCT) (vs. sham control) to address long-term neurobehavioral outcomes, including opioid relapse, craving, and sustained FMRI changes.

Study Overview

• Status: Completed
• Conditions: Opioid Dependence; Craving
• Intervention / Treatment: Device: tDCS; Device: sham tDCS

Detailed Description

This study has two phases. In phase one (UG3), the investigators propose to use FMRI to quantify changes in brain function and EEG to examine oscillatory brain changes as well as self-reported craving before and after administration of five sessions of tDCS+Cognitive Control Network (CCN) priming stimulation vs. sham tDCS+CCN priming (randomized control trial) in 60 opioid dependent participants who recently initiated buprenorphine or methadone. Participants in the first month of prescribed buprenorphine or methadone will be assessed using FMRI and EEG, once prior to tDCS and again one week later after completion of 5 sessions of tDCS+CCN priming. With a focus on the craving outcome, the investigators will use two task-based FMRI paradigms that challenge networks associated with craving (CR) and cognitive control (CCN), and will examine these and the salience network using resting state functional connectivity. In Phase 1, FMRI and EEG will be expected to provide 1) validation of expected network and oscillatory changes from tDCS-targeting and 2) an effect size for DLPFC vs sham stimulation. Go/no go criteria for the UG3 phase will be demonstration of greater FMRI change in any node of the CR or CCN networks or enhanced frontal theta power during a WM task AND greater change (at least 10% difference between conditions, controlling for baseline craving) in subjective craving measured during a cue reactivity task or outside the FMRI following the tDCS+CCN priming intervention compared to sham tDCS+CCN priming.

In phase 2, the investigators will perform a larger RCT using the same treatment protocol in 100 opioid dependent participants who recently initiated buprenorphine or methadone. Participants will be randomized to receive five sessions of tDCS+CCN priming stimulation vs. sham tDCS+CCN priming. Phase two will address long-term (3-month) neurobehavioral outcomes, including opioid relapse, craving, and sustained fMRI changes during a paradigm that challenges networks associated with craving (CR) and cognitive control (CCN). During the 12 weeks of buprenorphine or methadone maintenance treatment, the investigators will examine our primary clinical outcome, relapse (opioid use on >4 days per month and having an opioid positive urine screen), as well as days of opioid use.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ana M Abrantes, Ph.D.; Phone Number: 401-455-6440; Email: Ana_Abrantes@Brown.edu
• Study Contact Backup: Name: Julie Desaulniers, M.S.; Phone Number: 401-455-6219; Email: jdesaulniers@butler.org

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• current opioid dependence
• between 21-50 years of age
• recent initiation of buprenorphine or methadone (<30 days)

Exclusion Criteria:

• current criteria for a DSM-V diagnosis of bipolar disorder, schizophrenia, schizo-affective, schizophreniform, or paranoid disorder
• current suicidality
• evidence of neurocognitive dysfunction
• contraindications for tDCS (e.g seizure disorder)
• probation/parole requirements or an upcoming move that might interfere with protocol participation
• planning to terminate buprenorphine in less than 3 months
• scalp lesions near the tDCS electrode sites

Exclusion Criteria related to FMRI scanning are:

• history of neurological disorder (e.g., epilepsy, stroke, brain injury with loss of consciousness>10 min)
• impaired uncorrected vision
• MRI contraindications (e.g., claustrophobia, specific metallic implants and injuries, and pregnancy)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: tDCS; Each participant will undergo 5 consecutive (i.e., business days) sessions of active tDCS delivered to the DLPFC. During each session, participants are engaging in tasks that activate the cognitive control network.	Device: tDCS; Each participant will undergo 5 consecutive (i.e., business days) sessions of active tDCS delivered to the DLPFC. During each session, participants are engaging in tasks that activate the cognitive control network.
Sham Comparator: sham tDCS; Each participant will undergo 5 consecutive (i.e., business days) sessions of sham tDCS delivered to the DLPFC. During each session, participants are engaging in tasks that activate the cognitive control network.	Device: sham tDCS; Each participant will undergo 5 consecutive (i.e., business days) sessions of sham tDCS delivered to the DLPFC. During each session, participants are engaging in tasks that activate the cognitive control network.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in opioid craving	Visual Analog Craving scale (scoring: 1 - 10, with 1 = no craving and 10 = extreme craving; lower scores = less craving and higher scores = more craving)	2 week
change in the saliency network	activity in any node of the proposed network	2 week
change in the cognitive control network	activity in any node of the proposed network	2 week
change in EEG oscillatory targets	frontal theta power during working memory	2 week
lower rates of opioid relapse	Timeline follow-back interview	3 month

Collaborators and Investigators

• Sponsor: Butler Hospital
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Michael D Stein, M.D., Boston University; Principal Investigator: Ana M Abrantes, Ph.D., Butler Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2019
• Primary Completion (Actual): April 30, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: February 13, 2019
• First Submitted That Met QC Criteria: February 13, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders
• Other Study ID Numbers: 1810-001; UG3DA047793 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No