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

Overview

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.

Interventions

• Device Low-intensity focused ultrasound
  transcranially deliver focal energy into the accumbens nucleus in the brain
• Device false stimulus
  false stimulus

Primary outcome measures

• Substance craving intensity [Time frame: Before intervention, one week, a month, three months, six months, nine months, a year, one and half year and two years after treatment]
• Urinalysis [Time frame: Before intervention, one week, a month, three months, six months, nine months, a year, one and half year after treatment]
• Severity of Dependence [Time frame: 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 [Time frame: 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 (9)

• Mental health state [Time frame: 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 [Time frame: 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 [Time frame: Before intervention, three months, six months, a year, two year after treatment]
• functional Magnetic Resonance Imaging [Time frame: Before intervention, 24hours, a month, three months after treatment]
• Positron Emission Tomography [Time frame: Before intervention, a month after treatment]
• Anxiety state [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Before intervention, three months, six months, a year, two year after treatment]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Taiwan · 1 center

• National Taiwan University Hospital — Taipei

Identifiers

NCT: NCT07734623 · 202404026DINC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗