Craving, Opioid Dependence
Conditions
Brief summary
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 electroencephalographic (EEG), once prior to tDCS+CCN priming and again at the completion of 5 sessions of tDCS+CCN priming (one week later). EEG will provide validation of expected changes in these networks following tDCS stimulation of the DLPFC.
Detailed description
Investigators propose to use 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 EEG, once prior to tDCS and again one week later after completion of 5 sessions of tDCS+CCN priming. 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 enhanced frontal theta power during a WM task AND greater change (at least 10% difference between conditions, controlling for baseline craving) in subjective craving following the tDCS+CCN priming intervention compared to sham tDCS+CCN priming.
Interventions
DEVICEtDCS
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.
DEVICEsham 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.
Sponsors
National Institute on Drug Abuse (NIDA)
Butler Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Opioid Craving | 2 week | Penn Alcohol Craving (Modified for Opioids). This is a 5-item measure, with each item scored 0 to 6. Items are summed for a total score from 0 to 30. Higher scores = more craving. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EEG Theta Brainwave Activity | 2 weeks | Theta event rate is examined as the number of times/second that brainwaves within the theta frequency range (4-7 Hz). Higher event rates reflect more activity during working memory task. |
Countries
United States
Participant flow
Recruitment details
Participant recruitment started June 4, 2019 and was completed on 2/21/23. Participants were recruited from both clinical settings and through community advertisements.
Pre-assignment details
Once enrolled, participants were randomized at the beginning of their first tDCS session. If they did not attend that session, they were never randomized/assigned to a condition.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 27 |
| 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.
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. | 27 |
| Not Randomized Participants were randomized at the beginning of their first tDCS session. Enrolled participants who did not attend their first session (n=8) were never randomized. | 8 |
| Total | 62 |
Baseline characteristics
| Characteristic | Total | tDCS | Sham tDCS | Not Randomized |
|---|---|---|---|---|
| Age, Continuous | 34.08 years STANDARD_DEVIATION 7.96 | 33.19 years STANDARD_DEVIATION 7.44 | 34.48 years STANDARD_DEVIATION 7.91 | 35.75 years STANDARD_DEVIATION 10.38 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 4 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants | 23 Participants | 24 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Opioid Craving | 9.81 units on a scale STANDARD_DEVIATION 8.12 | 11.07 units on a scale STANDARD_DEVIATION 8.39 | 8.85 units on a scale STANDARD_DEVIATION 7.84 | 8.75 units on a scale STANDARD_DEVIATION 8.88 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 50 Participants | 23 Participants | 22 Participants | 5 Participants |
| Region of Enrollment United States | 62 participants | 27 participants | 27 participants | 8 participants |
| Sex: Female, Male Female | 25 Participants | 9 Participants | 14 Participants | 2 Participants |
| Sex: Female, Male Male | 37 Participants | 18 Participants | 13 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 |
| other Total, other adverse events | 1 / 27 | 2 / 27 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 |
Outcome results
Primary
Opioid Craving
Penn Alcohol Craving (Modified for Opioids). This is a 5-item measure, with each item scored 0 to 6. Items are summed for a total score from 0 to 30. Higher scores = more craving.
Time frame: 2 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tDCS | Opioid Craving | 8.92 units on a scale | Standard Deviation 1.1 |
| Sham tDCS | Opioid Craving | 8.32 units on a scale | Standard Deviation 1.12 |
p-value: 0.00895% CI: [-0.91, -0.15]Regression, Linear
Secondary
EEG Theta Brainwave Activity
Theta event rate is examined as the number of times/second that brainwaves within the theta frequency range (4-7 Hz). Higher event rates reflect more activity during working memory task.
Time frame: 2 weeks
Population: theta burst rate (per second) during the 2-back delay part of the working memory task
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tDCS | EEG Theta Brainwave Activity | .38 events per second | Standard Deviation 0.06 |
| Sham tDCS | EEG Theta Brainwave Activity | .33 events per second | Standard Deviation 0.05 |
p-value: 0.005ANCOVA