Opioid-use DisorderNCT04379115
Optimization of NIBS for Treatment of Addiction
A study testing Active Comparator: Active tDCS + Active TUS in people with Opioid-use Disorder and Chronic Pain, run by Case Western Reserve University at 3 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Opioid-use Disorder, Chronic Pain
- What is being tested?
- Active Comparator: Active tDCS + Active TUS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 126 participants
- Where
- 3 sitesUnited States
- Study dates
- 4 Apr 2021to 31 Oct 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must meet all of the following:
- Provide informed consent
- Age 18-85 years
- Diagnosis of opioid use disorder (DSM-5) with ongoing non-prescription opioid use confirmed by self-report and urine toxicology
- Report current opioid craving
- Enrolled in a certified Opioid Treatment Program and receiving methadone maintenance treatment
Show all 17Show fewer
- Stable methadone dose prior to enrollment
- Reside locally with no plans to relocate during the study Exclusion Criteria
- Participants will be excluded if they:
- Are pregnant
- Have frequent illicit stimulant use or acute stimulant intoxication
- Are using substances or medications that may interfere with study assessments (e.g., stimulant medications, buprenorphine-based therapies, naltrexone)
- Have significant neurological conditions (e.g., stroke, epilepsy, brain tumor), abnormal EEG findings, history of brain surgery, significant head injury, or unexplained syncope
- Have contraindications to noninvasive brain stimulation (e.g., metal in the head, implanted brain devices)
- Have moderate to severe depression or active suicidal ideation/behavior
- Have active malignancy
- Consume substances that could confound opioid toxicology results (e.g., poppy-seed products)
Who cannot join
None listed.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Spaulding Rehabilitation Hospital - 5th Floor - Neuromodulation Center
Cambridge, Massachusetts, 02138
Elly Pichardo, MD, 617-952-6158, epichardo@mgb.org
Felipe Fregni, MD, PhD, Fregni.Felipe@mgh.harvard.edu
- Recruiting
University Hospitals Cleveland Medical Center/ Dahms Clinical Research Unit
Cleveland, Ohio, 44106-1716
Salim Hayek, MD, 216-983-2085, salim.hayek@uhhospitals.org
Ciro R Estebanez, MD, PhD, cramoses@icloud.com
- Recruiting
University of Illinois Health/ University of Illinois at Chicago
Hinsdale, Illinois, 60612
Ming-Chieh Shun, PhD, mshun@uic.edu
Ciro Ramos Estebanez, MD, PhD, cramoses@icloud.com
About this study
Official title: 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.
- Conditions
- Opioid-use Disorder, Chronic Pain
- Being tested
- Active Comparator: Active tDCS + Active TUS, Sham Comparator: Sham tDCS + Sham TUS
- Medical subject headings
- Opioid-Related Disorders, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Comparator: Active tDCS + Active TUSDevice
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 TUSDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Active (tDCS) + Active TUS | Active comparator | Subjects in the experimental group will undergo 20 minutes of active transcranial direct current stimulation (tDCS) and active transcranial ultrasound (TUS) Receives: Device: Active Comparator: Active tDCS + Active TUS |
| Sham (tDCS) + Sham TUS | Sham comparator | Subjects in the sham group will undergo 20 minutes of sham transcranial direct current stimulation (tDCS) and sham transcranial ultrasound (TUS). Receives: Device: Sham Comparator: Sham tDCS + Sham TUS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: Measured for approximately 6 weeks
Secondary outcomes (16)
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: 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: 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: 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: 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: 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: Measured for approximately 6 weeks
Ultimatum Game:
This task evaluates reward, salience and executive network behavioral correlates
Measured: 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: 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: 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: 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: 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: 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: 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: 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: 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: Measured for approximately 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2020
- Study start4 Apr 2021
- Primary completion31 Oct 2027 (estimated)
- Study completion31 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid-use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- single-center, double-blinded, placebo controlled, randomized study.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 126 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Case Western Reserve University
- Sponsor type
- University, hospital or other
- Collaborators
- Highland Instruments, Inc.
- Responsible party
- Sponsor
- Investigators
- Ciro R Estebanez, MD PhD, Principal investigator, University Hospitals Cleveland Medical Center/ Case Western Reserve University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04379115
- Sponsor's protocol ID
- STUDY20190760
- Status last verified
- Mar 2026
- First submitted
- 21 Apr 2020
- Last updated
- 4 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimization of Non-Invasive Brain Stimulation for Treatment of Addiction
- ClinicalTrials.gov ID
- NCT04379115
- Acronym / sponsor ID
- STUDY20190760
- Conditions
- Opioid-use Disorder, Chronic Pain
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 126 participants (estimated)
- Lead sponsor
- Case Western Reserve UniversityUniversity, hospital or other
- Collaborators
- Highland Instruments, Inc.
- Study start
- 4 Apr 2021 (actual)
- Primary completion
- 31 Oct 2027 (estimated)
- Study completion
- 31 Oct 2027 (estimated)
- First posted
- 7 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- single-center, double-blinded, placebo controlled, randomized study.
| Arm | Type | Receives |
|---|---|---|
| Active (tDCS) + Active TUS | Active comparator | Device: Active Comparator: Active tDCS + Active TUSSubjects in the experimental group will undergo 20 minutes of active transcranial direct current stimulation (tDCS) and active transcranial ultrasound (TUS) |
| Sham (tDCS) + Sham TUS | Sham comparator | Device: Sham Comparator: Sham tDCS + Sham TUSSubjects in the sham group will undergo 20 minutes of sham transcranial direct current stimulation (tDCS) and sham transcranial ultrasound (TUS). |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Provide informed consent
- Age 18-85 years
- Diagnosis of opioid use disorder (DSM-5) with ongoing non-prescription opioid use confirmed by self-report and urine toxicology
- Report current opioid craving
- Enrolled in a certified Opioid Treatment Program and receiving methadone maintenance treatment
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active Comparator: Active tDCS + Active TUSDevice: 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. | Device | Active (tDCS) + Active TUS |
| Sham Comparator: Sham tDCS + Sham TUSDevice: 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. | Device | Sham (tDCS) + Sham TUS |
Primary outcome
Change in drug use from baseline.
Time frame: Measured for approximately 6 weeks
American Pain Foundation Pain/Medication Diary is used to monitor Drug Use overtime after stimulation for approximately 6 weeks.
16 secondary outcomes
Changes in the Verbal Rating Scale (VRS) for Pain
Time frame: Measured for approximately 6 weeks
Changes in pain as measured by the Visual Analog Scale (VAS)
Time frame: Measured for approximately 6 weeks
Safety measures
Time frame: Measured for approximately 6 weeks
Study 36-Item Short Form (SF-36)
Time frame: Measured for approximately 6 weeks
Patient Health Questionnaire (PHQ-9)
Time frame: Measured for approximately 6 weeks
Electroencephalography (EEG) recording:
Time frame: Measured for approximately 6 weeks
Ultimatum Game:
Time frame: Measured for approximately 6 weeks
Risk Task:
Time frame: Measured for approximately 6 weeks
Inhibitory Control Task:
Time frame: Measured for approximately 6 weeks
Opioid Cue-Exposure Task for Craving Assessment:
Time frame: Measured for approximately 6 weeks
Hair follicle drug test
Time frame: Measured for approximately 6 weeks
National Institute on Drug Abuse (NIDA)-Modified ASSIST (NM ASSIST)
Time frame: Measured for approximately 6 weeks
Obsessive-Compulsive Drinking/Drug Use Scale (OCDS)
Time frame: Measured for approximately 6 weeks
15-item Barrett Impulsivity scale
Time frame: Measured for approximately 6 weeks
National Institute on Drug Abuse (NIDA) Quick Screen
Time frame: Measured for approximately 6 weeks
Urine drug test
Time frame: Measured for approximately 6 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ciro R Estebanez, MD PhD principal investigator
University Hospitals Cleveland Medical Center/ Case Western Reserve University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active Comparator: Active tDCS + Active TUS in people with Opioid-use Disorder and Chronic Pain, run by Case Western Reserve University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kimberly Bass, RN (216-286-7250, kimberly.bass@uhhospitals.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in drug use from baseline. (time frame: Measured for approximately 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2026.