Opioid-use DisorderNCT04197921
Exablate for LIFU Neuromodulation in Patients With Opioid Use Disorder (OUD) and/or Other Substance Use Disorders (SUDs)
A study testing Exablate Model 4000 Type 2.0/2.1 in people with Opioid-use Disorder and Substance Use Disorders, run by InSightec at 4 sites in United States.
Trial summary
The purpose of this clinical trial is to investigate Low Intensity Focused Ultrasound (LIFU) using the Exablate® Model 4000 Type 2.0/2.1 as an adjunctive neuromodulatory treatment for OUD (Opioid Use Disorder) and/or other Substance Use Disorders (SUDs) by assessing its safety and tolerability in subjects with OUD. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Opioid-use Disorder, Substance Use Disorders
- What is being tested?
- Exablate Model 4000 Type 2.0/2.1
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 4 sitesUnited States
- Study dates
- 27 Nov 2019to 31 Dec 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Males and non-pregnant females, age 18 - 60 years old
- Subject meets DSM-5 criteria for OUD and/or other SUDs including alcohol (assessed via the SCID-5) of at least two years duration
- Subject is currently receiving outpatient treatment from the WVU Comprehensive Opioid Addiction Treatment Program (COAT), Intensive Outpatient Program (IOP) or any other program which implements the COAT model; residential or inpatient treatment from the WVU Center for Hope and Healing or an affiliated WVU hospital; or receiving outpatient/inpatient/residential treatment from similar programs that are well known to the research team. If the subject is prescribed medication for AUD or OUD (e.g. buprenorphine-naloxone, naltrexone), they will be on a stable dose of the medication for the 7 days prior to the procedure. Stable is defined as within the therapeutic range but does not require same exact dose for 7 days.
- Subject has been off opioids and other illicit substances, except for cannabis, confirmed via urine toxicology screen
- The NAc is apparent on MRI such that treatment targeting can be performed directly (visible on MRI) and indirectly (using other anatomical structures for measurements)
- Subject is able to communicate sensations during the Exablate Transcranial procedure
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- Subject is willing to cooperate with the study requirements including compliance with the regimen and completion of all study visits
- Subject is able to make own medical decisions as determined by the clinical team
- Subject has signed and received a copy of the approved informed consent form
Who cannot join
- Subjects who are taking medications which may adversely interact with MOUD (See Appendix B for full list). Being on one of these medications would not automatically exclude a participant from study participation, does not automatically exclude a prospective subject from study participation. If a prospective or current subject is taking any medication listed in Appendix B, the study investigator is responsible for determining whether the subject is eligible for inclusion or continued study participation."
- Subject with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices
- Subject with known intolerance or allergies to the MRI contrast agent gadolinium (GADOVIST®)
- Subject who are unable or unwilling to tolerate the required prolonged stationary position during treatment (approximately 2-3 hours)
- More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp
- Subject with implanted objects in the skull or the brain
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- Subject diagnosed with advanced kidney disease or on dialysis
- Subject with impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2
- Subject with known unstable cardiac status or severe hypertension including:
- Documented myocardial infarction within six months of enrollment
- Unstable angina on medication
- Unstable or worsening congestive heart failure
- Left ventricular ejection fraction below the lower limit of normal
- History of a hemodynamically unstable cardiac arrhythmia
- Cardiac pacemaker
- Severe hypertension (diastolic BP > 100 on medication)
- Subject with history of abnormal bleeding, hemorrhage, or coagulopathy
- Subject receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure
- Abnormal coagulation profile (PLT < 100,000/μl), PT (>13.9 sec) or PTT (>37.5 sec), and INR > 1.2. If values are outside the range of normal limits, any clinically significant value may be excluded as determined by a study investigator.
- Subject with cerebrovascular disease as determined by MRI according to the Fazekas criteria. Grades II and III on the Fazekas scale should be excluded
- Past or present diagnosis of schizophrenia, psychotic disorder, bipolar disorder, or untreated depression other than one determined to be substance induced (assessed via SCID-5)
- Score of greater than 17 on the Hamilton Depression Rating Scale (HAM-D) or increased risk of suicide based on any positive response regarding passive or active suicidal ideation with or without intent over the past 3 months or lifetime history of active suicidal ideation with intent on the Columbia-Suicide Severity Rating Scale (C-SSRS) at baseline
- History of suicide attempt
- Parental history of completed suicide
- Subject meet the criteria for Cluster A or B Personality Disorders (assessed via SCID-5-PD)
- Diagnosis of dementia or any other disorder which has led to a clinically significant cognitive impairment (assessed via NIHTB-CB)
- Subject with brain tumors
- Subject with chronic pulmonary disorders e.g. severe emphysema, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area
- Any known CNS infection or infection with the Human Immunodeficiency Virus (HIV) or Hepatitis C (HCV). A diagnosis of Hepatitis C (HCV) alone is not exclusionary as long as hepatic function laboratory values are deemed not clinically significant by a study investigator and are ≤ 1.5 times the upper limit of normal.
- Subject who has had deep brain stimulation or a prior stereotactic ablation of the NAc, basal ganglia or thalamus
- Subject who has been administered botulinum toxins into the arm, neck, or face for 5 months prior to baseline
- Subject who is currently participating in another clinical investigation with an active treatment arm
- Subject unwilling to abstain from illicit substance use during the course of the study
- Subject is considered to be a poor surgical or study candidate, which may include, but is not limited to the following: any medical, social, or psychological problem that could complicate the required procedures and evaluations of the study in the judgment of the investigator
- Subject is non-English speaking
- Subject is pregnant or planning to be pregnant
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Julia Zhu contact
United States4 sites, 4 recruiting
- Recruiting
University of Maryland, Baltimore
Baltimore, Maryland, 21201
Katie Henry, MS, 4103280939, khenry@som.umaryland.edu
Alexander Ksendzovsky, MD, PhD
- Recruiting
West Virginia University: Rockefeller Neuroscience Institute
Morgantown, West Virginia, 26505
Jennifer Marton, 304-293-5886, jennifer.marton@hsc.wvu.edu
Ali Rezai, MD
- Recruiting
Weill Cornell Medicine
New York, New York, 10065
Anna Angkatavanich, ana4037@med.cornell.edu
Michael Kaplitt, MD, PhD
- Not yet recruiting
Tampa General Hospital
Tampa, Florida, 33606
Carlos Rodriguez-Cosme, 8138447564, crodriguezcosme@tgh.org
Yarema Bezchlibnyk, MD, PhD
About this study
Official title: A Feasibility Clinical Trial of Exablate for Low Intensity Focused Ultrasound Neuromodulation in Patients With Opioid Use Disorder (OUD) and/or Other Substance Abuse Disorders (SUDs)
The purpose of this clinical trial is to investigate Low Intensity Focused Ultrasound (LIFU) using the Exablate® Model 4000 Type 2.0/2.1 as an adjunctive neuromodulatory treatment for OUD (Opioid Use Disorder) and/or other Substance Use Disorders (SUDs) by assessing its safety and tolerability in subjects with OUD.
- Conditions
- Opioid-use Disorder, Substance Use Disorders
- Being tested
- Exablate Model 4000 Type 2.0/2.1
- Medical subject headings
- Opioid-Related Disorders, Substance-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exablate Model 4000 Type 2.0/2.1Device
There are two treatment stages. In both stages, the subject will receive both the sham and active ExAblate treatment, and be evaluated for 90 days post-treatment for adverse events. During Stage 1 the subject will receive the moderate intensity Exablate LIFU procedure. During Stage2, the subject will receive the enhanced intensity ExAblate LIFU procedure. The subjects are blinded as to the order of the sham vs active treatment.
| Study group | Role | What they receive |
|---|---|---|
| Sham/Active ExAblate Treatment Stage 1 and 2 | Other | Subject will undergo both Treatment 1 (sham) and Treatment 2 (with enhanced intensity). Subjects are blinded to the order of the sham vs active treatment. Receives: Device: Exablate Model 4000 Type 2.0/2.1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of Treatment Emergent Adverse Events
Safety will be assessed by recording all adverse events that are treatment related. Each Adverse Event will be documented for patterns of occurence.
Measured: Post-ExAblate Procedure through 4 Month Follow-Up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2019
- Study start27 Nov 2019
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Opioid-use DisorderStudies of the same condition, open and under way.
- More trials run by InSightecThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- InSightec
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04197921
- Sponsor's protocol ID
- OUD001
- Status last verified
- Jun 2026
- First submitted
- 9 Dec 2019
- Last updated
- 26 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
Mahoney JJ, Thompson-Lake DGY, Ranjan M, Marton JL, Carpenter JS, D'Haese PF, Arsiwala T, Suffridge J, Farmer DL, Finomore VS, Tirumalai P, Hodder SL, Rezai AR. A case report of focused ultrasound neuromodulation of the bilateral nucleus accumbens for methamphetamine use disorder. Exp Clin Psychopharmacol. 2026 Jun;34(3):324-330. doi: 10.1037/pha0000793. Epub 2025 Sep 1.
PubMed 40892597Rezai A, Thompson-Lake DGY, D'Haese PF, Meyer N, Ranjan M, Farmer D, Finomore V, Marton JL, Hodder S, Carpenter J, Bhagwat A, Berry J, Tirumalai P, Adams G, Arsiwala TA, Blanke O, Mahoney JJ 3rd. Focused Ultrasound Neuromodulation: Exploring a Novel Treatment for Severe Opioid Use Disorder. Biol Psychiatry. 2025 Jul 1;98(1):56-64. doi: 10.1016/j.biopsych.2025.01.001. Epub 2025 Jan 9.
PubMed 39798597
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Feasibility Clinical Trial of Exablate for Low Intensity Focused Ultrasound Neuromodulation in Patients With Opioid Use Disorder (OUD) and/or Other Substance Abuse Disorders (SUDs)
- ClinicalTrials.gov ID
- NCT04197921
- Acronym / sponsor ID
- OUD001
- Conditions
- Opioid-use Disorder, Substance Use Disorders
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- InSightecIndustry (pharma, biotech, devices)
- Study start
- 27 Nov 2019 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 13 Dec 2019 (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 clinical trial is to investigate Low Intensity Focused Ultrasound (LIFU) using the Exablate® Model 4000 Type 2.0/2.1 as an adjunctive neuromodulatory treatment for OUD (Opioid Use Disorder) and/or other Substance Use Disorders (SUDs) by assessing its safety and tolerability in subjects with OUD.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sham/Active ExAblate Treatment Stage 1 and 2 | Other | Device: Exablate Model 4000 Type 2.0/2.1Subject will undergo both Treatment 1 (sham) and Treatment 2 (with enhanced intensity). Subjects are blinded to the order of the sham vs active treatment. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Males and non-pregnant females, age 18 - 60 years old
- Subject meets DSM-5 criteria for OUD and/or other SUDs including alcohol (assessed via the SCID-5) of at least two years duration
- Subject is currently receiving outpatient treatment from the WVU Comprehensive Opioid Addiction Treatment Program (COAT), Intensive Outpatient Program (IOP) or any other program which implements the COAT model; residential or inpatient treatment from the WVU Center for Hope and Healing or an affiliated WVU hospital; or receiving outpatient/inpatient/residential treatment from similar programs that are well known to the research team. If the subject is prescribed medication for AUD or OUD (e.g. buprenorphine-naloxone, naltrexone), they will be on a stable dose of the medication for the 7 days prior to the procedure. Stable is defined as within the therapeutic range but does not require same exact dose for 7 days.
- Subject has been off opioids and other illicit substances, except for cannabis, confirmed via urine toxicology screen
- The NAc is apparent on MRI such that treatment targeting can be performed directly (visible on MRI) and indirectly (using other anatomical structures for measurements)
Key exclusion criteria (36 listed)
- Subjects who are taking medications which may adversely interact with MOUD (See Appendix B for full list). Being on one of these medications would not automatically exclude a participant from study participation, does not automatically exclude a prospective subject from study participation. If a prospective or current subject is taking any medication listed in Appendix B, the study investigator is responsible for determining whether the subject is eligible for inclusion or continued study participation."
- Subject with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices
- Subject with known intolerance or allergies to the MRI contrast agent gadolinium (GADOVIST®)
- Subject who are unable or unwilling to tolerate the required prolonged stationary position during treatment (approximately 2-3 hours)
- More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp
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 |
|---|---|---|
| Exablate Model 4000 Type 2.0/2.1There are two treatment stages. In both stages, the subject will receive both the sham and active ExAblate treatment, and be evaluated for 90 days post-treatment for adverse events. During Stage 1 the subject will receive the moderate intensity Exablate LIFU procedure. During Stage2, the subject will receive the enhanced intensity ExAblate LIFU procedure. The subjects are blinded as to the order of the sham vs active treatment. | Device | Sham/Active ExAblate Treatment Stage 1 and 2 |
Primary outcome
Occurrence of Treatment Emergent Adverse Events
Time frame: Post-ExAblate Procedure through 4 Month Follow-Up
Safety will be assessed by recording all adverse events that are treatment related. Each Adverse Event will be documented for patterns of occurence.
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 26 Jun 2026.
- Derived from this study: PubMed 40892597Mahoney JJ, Thompson-Lake DGY, Ranjan M, Marton JL, Carpenter JS, D'Haese PF, Arsiwala T, Suffridge J, Farmer DL, Finomore VS, Tirumalai P, Hodder SL, Rezai AR. A case report of focused ultrasound neuromodulation of the bilateral nucleus accumbens for methamphetamine use disorder. Exp Clin Psychopharmacol. 2026 Jun;34(3):324-330. doi: 10.1037/pha0000793. Epub 2025 Sep 1.
- Derived from this study: PubMed 39798597Rezai A, Thompson-Lake DGY, D'Haese PF, Meyer N, Ranjan M, Farmer D, Finomore V, Marton JL, Hodder S, Carpenter J, Bhagwat A, Berry J, Tirumalai P, Adams G, Arsiwala TA, Blanke O, Mahoney JJ 3rd. Focused Ultrasound Neuromodulation: Exploring a Novel Treatment for Severe Opioid Use Disorder. Biol Psychiatry. 2025 Jul 1;98(1):56-64. doi: 10.1016/j.biopsych.2025.01.001. Epub 2025 Jan 9.
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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.
Julia Zhu contact
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exablate Model 4000 Type 2.0/2.1 in people with Opioid-use Disorder and Substance Use Disorders, run by InSightec at 4 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 9 inclusion and 36 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 26 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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. 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 Kingsley Nwaogu (2143048264, clinicalresearchquestions@insightec.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of Treatment Emergent Adverse Events (time frame: Post-ExAblate Procedure through 4 Month Follow-Up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04197921, which also lists 2 linked publications.
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 26 Jun 2026.