Bilateral Nucleus Accumbens Focused Ultrasound Neuromodulation for Stimulant Use Disorder

Safety and Preliminary Efficacy of Bilateral Nucleus Accumbens-Targeted Low-Intensity Focused Ultrasound Neuromodulation Using ExAblate 4000 Type 2.1 in Patients With Stimulant Use Disorder: A Single-Center, Prospective, Single-Arm, Open-Label, Investigator-Initiated Feasibility Trial

The purpose of this clinical trial is to evaluate the initial safety and efficacy of the ExAblate Model 4000 Type 2.1 surgical device for nucleus accumbens (NAc) neuromodulation in patients with psychostimulant use disorder (PUD).

Study Overview

• Status: Recruiting
• Conditions: Psychostimulant Use Disorder(PUD)
• Intervention / Treatment: Device: ExAblate 4000 Type 2.1

Detailed Description

This prospective, single-center, single-arm, open-label feasibility trial is designed to evaluate the safety and preliminary efficacy of nucleus accumbens (NAc)-targeted neuromodulation using the ExAblate 4000 Type 2.1 system in patients with psychostimulant use disorder (PUD).

Potential participants with PUD who are receiving standard treatment for substance use disorder will be informed about the study and invited to participate. Individuals who voluntarily provide written informed consent will undergo screening assessments to determine eligibility according to the predefined inclusion and exclusion criteria. Eligible participants will then be enrolled in the study.

At Visit 2, participants will undergo focused ultrasound neuromodulation targeting the bilateral NAc using the ExAblate 4000 Type 2.1 system. The procedure will be performed under magnetic resonance imaging guidance. Following completion of the procedure, participants will be clinically observed for at least 2 hours and assessed for any procedure- or device-related adverse events. Participants who discontinue the study because of an adverse event will continue to be followed as clinically appropriate until the event has resolved or stabilized, or until the investigator determines that further follow-up is no longer necessary.

Participants will return for follow-up assessments at Visit 3 (Day 7 ± 2), Visit 4 (Day 30 ± 7), Visit 5 (Day 90 ± 7), and Visit 6 (Day 180 ± 7) after the focused ultrasound procedure. Safety assessments will include monitoring for adverse events and clinically relevant neurological or medical changes. Efficacy assessments will include urine toxicology testing for psychostimulant and illicit drug use, assessment of time to relapse, evaluation of substance craving, psychiatric and behavioral assessments related to mood, anxiety, attention, and impulsivity, and assessment of cognitive function. Functional magnetic resonance imaging, including a drug-cue reactivity paradigm, will also be performed at predefined study time points to evaluate longitudinal changes in neural responses associated with drug craving.

All participants will complete the final study evaluation at Visit 6 (Day 180 ± 7). Participants with unresolved adverse events may continue to be followed beyond the final scheduled visit when considered clinically necessary by the investigator.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• South Korea
  • Seoul
    • Seoul, Seoul, South Korea, 02841
      • Recruiting
      • Korea University Anam Hospital
      • Contact: Kweon, eun jung; Phone Number: 82+02-920-5696; Email: kweonej@kumc.or.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults between the ages of 19 and 60

2. Subject is diagnosed with a DSM-5 psychostimulant* use disorder (PUD) by a board certified psychiatrist.

   *Psychostimulants: Methamphetamine, cocaine, and other stimulants

3. Subject is currently receiving standard substance use disorder inpatient treatment or an intensive outpatient program
4. Subject has been off psychostimulants and other illicit drugs, confirmed via urine toxicology screen
5. Subject has not regularly used illegal drugs other than psychostimulants more than once a month in the past six months
6. 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)
7. Subject is able to communicate sensations during the investigational procedure
8. Subject has made a voluntary decision to participate in this clinical trial and has given written consent.
9. Subject is willing to comply to the protocol

Exclusion Criteria:

1. Subject with standard contraindication for MR imaging, such as non-MRI compatible implanted metallic devices.
2. Subject with known allergies to the MRI contrast agent gadolinium (Gadovist®) or contraindication (such as untreated hypokalemia).
3. Subject who are unable or unwilling to tolerate the required prolonged stationary position during treatment (approximately 2-3 hours)
4. More than 30% of the skull area traversed by the sonication pathyway is covered by scars, scalp disorder (e.g., eczema), or atrophy of the scalp.
5. Subject with implanted objects in the skull or brain
6. Subject diagnosed with advanced kidney disease or on dialysis
7. Subjet with impaired renal function with estimated glomerular filtration rate less than 30 mL/min/1.73 m 2

8. 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 (LVEF) below the lower limit of normal
   • History of hemodynamically unstable cardiac arrhythmias
   • Cardiac pacemaker
   • Severe hypertension (diastolic blood pressure over 100 on medication)
9. Subject has a history of abnormal bleeding or coagulopathy
10. Subject is receiving anticoagulant (e.g., warfarin) or antiplatelet (e.g., aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk of hemorrhage (e.g., Avastin) within one month of focused ultrasound procedure

11. Subject has blood coagulation test results outside the normal range

    • PLT<100,000/μL
    • PT>13.9 seconds or PTT>37.5 seconds
    • INR>1.2
12. Subject with cerebrovascular disease as determined by MRI according to Fazekas score
13. Subject with a past or current diagnosis of schizophrenia, psychotic disorder, bipolar disorder, or untreated depression other than one determined to be substance induced
14. 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
15. Diagnosis of dementia or any other disorder which has led to a clinically significant cognitive impairment (assessed via NIHTB-CB)
16. Subject with brain tumors
17. Subject with chronic pulmonary disorders e.g. severe emphysema, pulmonary vasculitis, or other casues of reduced pulmonary vascular cross-sectional area.
18. Any known CNS infection or infection with the human immunodeficiency virus (HIV)
19. Subject who has had deep brain stimulation or a prior stereostatic ablation of the NAc, basal ganglia, or thalamus
20. Subject who has been administered botulinum toxins into to the arm, neck, or face for 5 months prior to baseline
21. Subject unwilling to refrain from using illicit drugs while participating in this clinical trial
22. Subject is pregnant or nursing women

23. For women of childbearing potential*, who do not agree to use clinically appropriate contraception** for the duration of the clinical trial

    *Definition of women of childbearing age: means women who have experienced menarche, have not been surgically sterilized (hysterectomy or bilateral oophorectomy), or are not post-menopausal, defined as amenorrhea for 12 months or more for no other reason.

    **Clinically appropriate contraception: defined as "[intrauterine device (e.g., Loop, Mirena), chemical barrier method (spermicide), or subdermal implantable contraceptive device (e.g., Implanon)] + physical barrier method (male or female)" for women, tubal surgery, or laparoscopic contraception (a type of tubal ligation).

24. Other, if the investigator determines that participation in the clinical trial is inappropriate ethically or because it may affect the outcome of the clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment arm: Visit 2(Procedure)	Device: ExAblate 4000 Type 2.1; In treatment arm, the subject will receive device application(bilateral NAc FUS; Visit 2) Subjects will return to the site at Visit 3 (7±2 days post device application), Visit 4 (30±7 days post device application), Visit 5 (90±7 days post device application), and Visit 6 (180±7 days post device application) for safety and efficacy assessments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success rate of psychostimulant abstinence (%)	Percentage of subjects with no detectable psychostimulants and other illicit drugs by urine toxicology screening after application	7, 30, 90, and 180 days after device application

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to relapse (in days)	Time in days from active sonication to the first positive urine toxicology result indicating psychostimulant relapse. Participants without a positive urine toxicology result are followed through Day 180.	6 months
Visual Analog Scale rating of craving severity	Change in substance craving visual analog scale (VAS, 0-10) score after device application. Craving is rated on a 0-10 visual analog scale, where 0 indicates no craving and 10 indicates the strongest craving ever.	Baseline to 7, 30, 90, and 180 days after device application
Assessments related to mood/anxiety/attention/impulsivity	Change (in points) in assessments of mood/anxiety/attention/impulsivity	Baseline to 7, 30, 90, and 180 days after device application
Assessment of cognitive function	Change in Cognitive Function Assessment (points) Post-device application	Baseline to 180 days after device application
Evaluation of resting-state functional connectivity (RSFC) and fMRI drug cue reactivity (FDCR)	Change in resting-state functional connectivity (RSFC) and fMRI drug cue reactivity (FDCR) after device application. RSFC assesses longitudinal changes in functional connectivity across brain networks at rest, while FDCR assesses longitudinal changes in BOLD responses to drug-related versus neutral cues.	Baseline to 7 days and 90 days after device application

Collaborators and Investigators

• Sponsor: Korea University Anam Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: June 19, 2024
• First Submitted That Met QC Criteria: June 19, 2024
• First Posted (Actual): June 25, 2024

Study Record Updates

• Last Update Posted (Actual): August 24, 2026
• Last Update Submitted That Met QC Criteria: August 20, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: neuromodulation; ExAblate 4000 Type 2.1; Psychostimulant use disorder
• Other Study ID Numbers: KUAHPD-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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