Optimization of NIBS for Treatment of Addiction

Study Overview
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Brief Summary
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The purpose of this study is to assess the effects of transcranial Direct Current Stimulation (tDCS) applied in conjunction with Transcranial Ultrasound (TUS) for the treatment of addiction in opiate use disorder with chronic pain. The investigators hypothesize that there will be a decrease in drug use and improved psychosocial assessments with active stimulation, when compared to sham stimulation.

Official Title
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Optimization of Non-Invasive Brain Stimulation for Treatment of Addiction

Conditions
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Opioid-use Disorder, Chronic Pain

Intervention / Treatment
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* Device: Active Comparator: Active tDCS + Active TUS
* Device: Sham Comparator: Sham tDCS + Sham TUS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Providing informed consent to participate in the study. 18 to 85 years old. Having a diagnosis of OUD, in the setting of CP: OUD of more than 6 months duration as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-5) [64] and a positive urine toxicology screen. or OUD patients who still feel craving or have not received more than 60 mg of methadone/day from the Methadone program. Lives in the immediate area with no plans to relocate Exclusion Criteria: The subject is pregnant. Recently started on antiepileptic drug therapy. History of illegal stimulant use as demonstrated by urine toxicology. . Ingestion of poppy seeds or herbal teas containing Papaveris Fructus (may cause a positive opiate test for morphine, codeine [66, 67]). History of neurological disorders involving stroke, brain tumors, or epilepsy as self- reported (note patients will also be evaluated via electroencephalography (EEG) at baseline 1 week prior to stimulation and any patient showing abnormal EEG activity will be removed)). History of unexplained fainting spells as self-reported. History of head injury resulting in more than a momentary loss of consciousness as self-reported. History of brain surgery as self-reported. Contraindications to tDCS applied in conjunction with TUS: Metal in the head, or Implanted brain medical devices. Suffering from severe depression (with a score of >30 in the Beck Depression Inventory (BDI), PHQ-9≥10). Active malignancy. History of suicidal behavior or suicide attempts.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: single-center, double-blinded, placebo controlled, randomized study.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active (tDCS) + Active TUS<br>Subjects in the experimental group will undergo 20 minutes of active transcranial direct current stimulation (tDCS) and active transcranial ultrasound (TUS) | Device: Active Comparator: Active tDCS + Active TUS<br>* Device: Active comparator device: Active transcranial Direct Current Stimulation (tDCS). Subjects will receive 20 minutes of active tDCS. During each Active stimulation session, stimulation will be applied for the full 20 minutes. Device: Active comparator device: Active Transcranial Ultrasound (TUS). Subjects will receive 20 minutes of active Transcranial Ultrasound (TUS). During active stimulation the (TUS) will be active for the full 20 minutes.<br>|
| Sham Comparator: Sham (tDCS) + Sham TUS<br>Subjects in the sham group will undergo 20 minutes of sham transcranial direct current stimulation (tDCS) and sham transcranial ultrasound (TUS). | Device: Sham Comparator: Sham tDCS + Sham TUS<br>* Device: SHAM Comparator Device: transcranial Direct Current Stimulation (tDCS) Subjects will receive 20 minutes of sham tDCS. In the sham group, the tDCS device will not be active for the full 20 minutes. Device: Transcranial Ultrasound (TUS) Subjects will receive 20 minutes of sham TUS. During sham stimulation the ultrasound will not be active for the full 20 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in drug use from baseline. | American Pain Foundation Pain/Medication Diary is used to monitor Drug Use overtime after stimulation for approximately 6 weeks. | Measured for approximately 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the Verbal Rating Scale (VRS) for Pain | Changes in VRS for Pain will be measured in order to determine if tDCS + ESSTIM is effective in reducing the pain of subjects with Chronic Pain (CP) and Opioid Use Disorder(OUD) when compared to the SHAM group.Verbal Rating Scale (VRS) for Pain is a categorical scale of pain with categories: none, mild, moderate, severe pain intensity. | Measured for approximately 6 weeks | 
| Changes in pain as measured by the Visual Analog Scale (VAS) | Changes in VAS for Pain will be measured in order to determine if tDCS + ESSTIM is effective in reducing the pain of subjects with Chronic Pain (CP) and Opioid Use Disorder(OUD) when compared to the SHAM group.Visual Analog Scale (VAS) for Pain will assess a patient's pain intensity on a scale from 0 (no pain) to 10 (worst pain imaginable). | Measured for approximately 6 weeks | 
| Safety measures | The investigators will measure safety through a standardized neurological exam, which will include the assessment of cognitive domains including memory, attention, mood (scaled as normal or abnormal). | Measured for approximately 6 weeks | 
| Study 36-Item Short Form (SF-36) | This is a health survey using a scale from 0 (worst) to 100 (best) | Measured for approximately 6 weeks | 
| Patient Health Questionnaire (PHQ-9) | This questionnaire screens for depression with a score of 0 (best) to 27 (worst) | Measured for approximately 6 weeks | 
| Electroencephalography (EEG) recording: | previous: EEG recording: On the first baseline visit, on the first day of Week 1, at the end of each stimulation week, and at the follow up visits. EEG recordings will be taken to monitor changes in power in different frequency bands including (theta, alpha, beta and gamma) for 20 min. | Measured for approximately 6 weeks | 
| Ultimatum Game: | This task evaluates reward, salience and executive network behavioral correlates | Measured for approximately 6 weeks | 
| Risk Task: | The task is designed to analyze the relationship between prediction and reward (and penalty) is associated with the choice of the least likely outcome, and the smallest reward (and penalty). | Measured for approximately 6 weeks | 
| Inhibitory Control Task: | We will assess the interaction between reward processing (via the presence or absence of reward) and mechanisms of inhibitory control. | Measured for approximately 6 weeks | 
| Opioid Cue-Exposure Task for Craving Assessment: | A set of randomized videos showing scenes of people using opioids will aid assessment of craving. | Measured for approximately 6 weeks | 
| Hair follicle drug test | A hair follicle drug test screens for illicit drug use and the misuse of prescription medication. The sample is then analyzed for signs of drug use over 90 days. The results will be measured as positive or negative. | Measured for approximately 6 weeks | 
| National Institute on Drug Abuse (NIDA)-Modified ASSIST (NM ASSIST) | Clinician's Screening Tool for Drug Use in General Medical Settings which implements a scale from 0-3 Low Risk, 3-26  Moderate Risk, and 27+ High Risk | Measured for approximately 6 weeks | 
| Obsessive-Compulsive Drinking/Drug Use Scale (OCDS) | This measure reflects obsessionality and compulsivity related to craving and drinking behavior with a total score ranging from 0 to 64 (with 64 being the worst). | Measured for approximately 6 weeks | 
| 15-item Barrett Impulsivity scale | 15-item Barrett Impulsivity scale is used to measure impulsivity with a total score ranging from 15 to 60 (with 15 lower level of impulsivity and 60 higher levels of impulsivity. | Measured for approximately 6 weeks | 
| National Institute on Drug Abuse (NIDA) Quick Screen | The NIDA Quick Screen is a validated instrument designed to assist providers in screening adults for substance use which has a yes/no scale (with no being best and yes being worse) | Measured for approximately 6 weeks | 
| Urine drug test | A Urine drug test screens for illicit drug use and the misuse of prescription medication. The sample is then analyzed for signs of drug use during the past few days. The results will be measured as positive or negative. | Measured for approximately 6 weeks |