Applying Low-Intensity Focused Ultrasound in Treating Severe Substance Use Disorder: Tolerability and Effectiveness

The goal of this clinical trial is to investigate the safety and efficacy of applying low-intensity focused ultrasound targeting the nucleus accumbens in individuals with opioid or amphetamine use disorders. The main questions it aims to answer is:

- Low-intensity focused ultrasound targeting the nucleus accumbens demonstrates sufficient safety and predictable therapeutic efficacy in individuals with opioid or amphetamine use disorders.

Participants will:

• Received Low-intensity focused ultrasound neuromodulation once
• Visit the clinic for checkups and asessment at 1 week, 1 month, 3 months, 6 months, 9 months, 1 year, 1.5 years, and 2 years after received Low-intensity focused ultrasound neuromodulation.

Study Overview

• Status: Recruiting
• Conditions: Opioid Use Disorder, Severe; Amphetamine Use Disorder
• Intervention / Treatment: Device: Low-intensity focused ultrasound; Device: false stimulus

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chien Yi-Ling; Phone Number: #266013 +886 2-2312-3456; Email: ntuh.peers@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan, 100229
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Chien Yi-Ling; Phone Number: #266013 +886 2-2312-3456; Email: ntuh.peers@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Meets the DSM-5 criteria for opioid use disorder or amphetamine use disorder, with a severity level of severe, and does not currently meet the criteria for in sustained remission;
• Within 7 days prior to the screening assessment, the participant must have been receiving a stable dose of medication treatment, such as methadone, buprenorphine/naloxone, or naltrexone;
• Within 7 days prior to the screening assessment, the participant must have abstained from illicit substances and alcohol, and must have a negative urine drug test;
• The bilateral nucleus accumbens must be clearly identifiable on magnetic resonance imaging (MRI), such that they are sufficient for treatment targeting and for indirect measurement from other anatomical structures;
• The participant must be able to communicate effectively and express their feelings and experiences during the study procedures;
• The participant must be willing to comply with the study requirements, including adherence to prescribed medications and cooperation with study visits and assessments.

(The participant must have the capacity to make independent medical decisions, as determined by the clinical team.)

Exclusion Criteria:

• Presence of neurological disorders or major psychiatric disorders, such as acute-phase schizophrenia spectrum disorder, acute-phase bipolar disorder, acute-phase major depressive disorder, severe cognitive impairment, or recent suicidal ideation or plan;
• Antisocial personality disorder;
• Occurrence of major physical health problems within 6 months prior to the trial, including: Cardiovascular or hemodynamic abnormalities, such as heart failure, arrhythmia, tachycardia or bradycardia (>100 bpm or <60 bpm), abnormal systolic blood pressure (>180 mmHg or <90 mmHg), or abnormal diastolic blood pressure (>180 mmHg); Platelet or coagulation abnormalities (INR > 1.5) or current use of medications that may cause anticoagulation, such as warfarin or Avastin; Renal dysfunction (eGFR < 30 mL/min/1.73 m²) or ongoing hemodialysis; Severe infection; Immunocompromised status; History of intracranial hemorrhage, intracranial aneurysm, cerebrovascular events within the past 6 months, or brain tumor; Neurological diseases, such as stroke, epilepsy, Parkinson's disease, dementia, or related disorders; Any other physical illness that, based on clinical evaluation, may pose a significant risk to physical function or life during treatment.
• Participants who, upon evaluation, are deemed unsuitable for MR-guided focused ultrasound treatment, including those with a low skull density ratio (<0.4), intracranial implants, or energy-absorbing structures or sensitive tissues along the ultrasound beam path that cannot be avoided (such as prior ventriculoperitoneal shunt sites, surgical metal clips, significant calcifications, extensive scarring, or any rigid implants). During the pre-treatment evaluation, a head CT scan will be performed to determine whether the skull density ratio is suitable for focused ultrasound treatment. Based on prior theoretical evidence, an excessively low skull density ratio may reduce the efficiency of MR-guided focused ultrasound and increase the risk of adverse effects, and therefore such participants are considered unsuitable for focused ultrasound treatment.
• Structural abnormality of either side of the nucleus accumbens;
• Contraindications to MRI, such as claustrophobia, allergy to MRI contrast agents, or the presence of metallic implants incompatible with MRI;
• Contraindications to PET imaging, such as allergy to radiopharmaceutical contrast agents;
• Inability to comply with trial-related instructions, lack of legal/behavioral capacity, or lack of motivation to receive treatment;
• Pregnancy or breastfeeding;
• Scalp atrophy or poor wound healing of the scalp;
• Any other condition that, in the physician's judgment, makes the participant unsuitable for enrollment in the clinical trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group	Device: Low-intensity focused ultrasound; transcranially deliver focal energy into the accumbens nucleus in the brain
Sham Comparator: Control group	Device: false stimulus; false stimulus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Substance craving intensity	Using visual analogue scale (VAS) to measure craving intensity, higher score shows greater craving for substance	Before intervention, one week, a month, three months, six months, nine months, a year, one and half year and two years after treatment
Urinalysis	Whether urine screening tests are positive for opioids and amphetamines. The intervention will be considered effective if the positivity rate decreases by 50% one month after the intervention compared with the time of intervention.	Before intervention, one week, a month, three months, six months, nine months, a year, one and half year after treatment
Severity of Dependence	Using Severity of Dependence Scale (SDS) to measure craving intensity, higher score shows greater severity of Dependence	Before intervention, one week, a month, three months, six months, nine months, a year, one and half year and two years after treatment
Stimulant Relapse Risk	Using Stimulant Relapse Risk Scale (SRRS) to measure craving intensity, higher score shows higher stimulant relapse risk	Before intervention, one week, a month, three months, six months, nine months, a year, one and half year and two years after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mental health state	Using Patient Health Questionnaire (PHQ-9) to measure participants' mental health state, greater scores of these scales shows worse mental health state.	Before intervention, one week, a month, three months, six months, nine months, a year, one and half year and two years after treatment
Executive function assessment	Using Behavior Rating Inventory of Executive Function (BRIEF) to assess how well executive function of participants is.	Before intervention, one week, a month, three months, six months, nine months, a year, one and half year and two years after treatment
Neuropsychological function assessment	Using Cambridge Gambling Task (CGT) to assess Neuropsychological function since the intervention is to nucleus accumbens and could potentially affect Neuropsychological function.	Before intervention, three months, six months, a year, two year after treatment
functional Magnetic Resonance Imaging	Because the nucleus accumbens, the intervention target, may be involved in craving, functional magnetic resonance imaging (fMRI) will be used to assess changes in brain activation during the craving task before and after treatment.	Before intervention, 24hours, a month, three months after treatment
Positron Emission Tomography	Because neuromodulation may affect metabolic activity in the nucleus accumbens, positron emission tomography (PET) will be used to measure cerebral metabolism and compare changes before and after the intervention.	Before intervention, a month after treatment
Anxiety state	Using Hamilton Anxiety Rating Scale (HAM-A), and Generalized Anxiety Disorder questionnaire(GAD-7) to measure participants' anxiety state, greater scores of these scales shows worse anxiety state.	Before intervention, one week, a month, three months, six months, nine months, a year, one and half year and two years after treatment
Depression state	Using Hamilton Depression Rating Scale (HAM-D), to measure participants' mental health state, greater scores of these scales shows worse depression state.	Before intervention, one week, a month, three months, six months, nine months, a year, one and half year and two years after treatment
Attendtion state	Using Adult ADHD Self-Report Scale (ASRS) to assess how well attention state of participants is.	Before intervention, one week, a month, three months, six months, nine months, a year, one and half year and two years after treatment
Working memory capacity	Using N-back test to assess working memory capacity since the intervention is to nucleus accumbens and could potentially affect Neuropsychological function.	Before intervention, three months, six months, a year, two year after treatment

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: March 12, 2026
• First Submitted That Met QC Criteria: July 27, 2026
• First Posted (Actual): July 29, 2026

Study Record Updates

• Last Update Posted (Actual): July 31, 2026
• Last Update Submitted That Met QC Criteria: July 30, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders
• Other Study ID Numbers: 202404026DINC

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