Optimization of NIBS for Treatment of Addiction

Optimization of Non-Invasive Brain Stimulation for Treatment of Addiction

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Pain; Opioid-use Disorder
• Intervention / Treatment: Device: Active Comparator: Active tDCS + Active TUS; Device: Sham Comparator: Sham tDCS + Sham TUS

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kimberly Bright; Phone Number: (216) 844-0474; Email: kimberly.Bright@uhhospitals.org
• Study Contact Backup: Name: Megan Miller; Phone Number: 216-844-4720; Email: megan.miller3@uhhospitals.org

Study Locations

• United States
  • Illinois
    • Hinsdale, Illinois, United States, 60612
      • Recruiting
      • University of Illinois Health/ University of Illinois at Chicago
      • Contact: Ciro Ramos Estebanez; Email: cramoses@icloud.com
      • Contact: Elizabeth Villagrana; Phone Number: 312-413-0483; Email: nevilla@uic.edu
      • Principal Investigator: Ciro Ramos Estebanez, MD, PhD
  • Ohio
    • Cleveland, Ohio, United States, 44106-1716
      • Recruiting
      • University Hospitals Cleveland Medical Center/ Dahms Clinical Research Unit
      • Contact: Ciro R Estebanez, MD, PhD; Email: cramoses@icloud.com
      • Contact: Jillian Russell, MSN, RN-BC; Phone Number: 216-844-4901; Email: Jillian.Russell@uhhospitals.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Providing informed consent to participate in the study.
2. 18 to 85 years old.

3. 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.
4. Lives in the immediate area with no plans to relocate

Exclusion Criteria:

1. The subject is pregnant.
2. Recently started on antiepileptic drug therapy.
3. History of illegal stimulant use as demonstrated by urine toxicology.
4. . Ingestion of poppy seeds or herbal teas containing Papaveris Fructus (may cause a positive opiate test for morphine, codeine [66, 67]).
5. 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)).
6. History of unexplained fainting spells as self-reported.
7. History of head injury resulting in more than a momentary loss of consciousness as self-reported.
8. History of brain surgery as self-reported.

9. Contraindications to tDCS applied in conjunction with TUS:

   • Metal in the head, or
   • Implanted brain medical devices.
10. Suffering from severe depression (with a score of >30 in the Beck Depression Inventory (BDI), PHQ-9≥10).
11. Active malignancy.
12. History of suicidal behavior or suicide attempts.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active (tDCS) + Active TUS; 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; 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.
Sham Comparator: Sham (tDCS) + Sham TUS; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Case Western Reserve University
• Collaborators: Highland Instruments, Inc.
• Investigators: Principal Investigator: Ciro R Estebanez, MD PhD, University Hospitals Cleveland Medical Center/ Case Western Reserve University

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2020
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: April 21, 2020
• First Submitted That Met QC Criteria: May 6, 2020
• First Posted (Actual): May 7, 2020

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Pain; Neurologic Manifestations; Narcotic-Related Disorders; Chronic Pain; Opioid-Related Disorders
• Other Study ID Numbers: STUDY20190760

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No