Safety and Feasibility of Next-Generation Dome Helmet (NGDH) for Focused Ultrasound Neuromodulation in Substance Use Disorder (SUD)

Assessment of Safety and Feasibility of Focused Ultrasound (FUS) Next Generation Dome Helmet (NGDH) to Perform Neuromodulation in Patients With Substance Use Disorder (SUD)

The goal of this clinical trial is to evaluate the safety, feasibility, and preliminary clinical benefit of focused ultrasound (FUS) neuromodulation using the FUS Next Generation Dome Helmet (NGDH) in adults with treatment-resistant moderate-to-severe substance use disorder (SUD).

The main questions it aims to answer are:

Can FUS neuromodulation be safely delivered to the nucleus accumbens (NAc) and/or anterior insula (aI)? Does FUS neuromodulation result in reduced substance use severity, as measured by Timeline Followback (TLFB), by 4 weeks post-treatment?

Participants will:

Complete baseline clinical assessments, questionnaires, imaging, and safety assessments.

Undergo two MRI-guided FUS neuromodulation sessions approximately 4 weeks apart.

Attend follow-up visits for safety monitoring, symptom assessments, quality-of-life measures, and additional imaging where applicable.

Study Overview

• Status: Recruiting
• Conditions: Substance Use Disorder (SUD)
• Intervention / Treatment: Device: Next Generation Dome Helmet (NGDH)

Detailed Description

A total of 20 participants with treatment-resistant moderate-to-severe substance use disorder (SUD) will be enrolled and treated in this study. Participants will be enrolled from the local practices of the psychiatrists/addiction physicians involved in the study and through outside referrals, including physician referrals or self-referrals. Patient eligibility will be assessed at a screening appointment by the study coordinator and a physician associated with the study. The anticipated enrollment period is approximately two years.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anusha Baskaran, PhD; Phone Number: 61650 416-480-6100
• Study Contact Backup: Name: Nir Lipsman, MD, PhD, FRCSC; Phone Number: (416)-480-6954; Email: Nir.Lipsman@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Soraly Blanco; Phone Number: 61519 416-480-6100; Email: jaana.leppala@sunnybrook.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Must be deemed to have capacity to provide informed consent (determined by the investigator)
2. Age between 18 to 70 (inclusive)
3. Diagnosis of SUD (cannabis, alcohol, ketamine, stimulant, opioid or nicotine/tobacco use disorder) in the moderate to severe range according to the DSM-5
4. Previous ≥2 pharmacotherapy trials for the diagnosed SUD according to guideline-concordant, evidence-based care
5. On a stable regimen of their psychiatric medications for 30 days before enrolment.

Exclusion Criteria:

1. Pregnant or intending to be pregnant during the study
2. Known active seizure disorder, significant head injury with an imaging verified lesion
3. Medical illness that is deemed to be unstable or may confound the effects of the intervention
4. Not eligible for 3-Tesla MRI (i.e. MRI-incompatible pacemaker)
5. Unable to reliably attend the required screening, treatment, and follow up appointments.
6. Severe claustrophobia, identified by the subject to be a limiting factor preventing MRI.
7. Scores 18 or below on Montreal Cognitive Assessment (MoCA)
8. Weighs 250 lbs or more.

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: Focused Ultrasound Neuromodulation - NAc First; Participants will undergo two focused ultrasound (FUS) neuromodulation sessions spaced four weeks apart. Treatments will target the nucleus accumbens and anterior insula. One of the two sessions may include sham exposure or active control sonication.

Device: Next Generation Dome Helmet (NGDH); Focused ultrasound (FUS) neuromodulation delivered using the Next Generation Dome Helmet (NGDH) system under MRI guidance. The device delivers low-intensity pulsed ultrasound to targeted brain regions, including the nucleus accumbens and anterior insula, to modulate neural activity. Participants will undergo two treatment sessions spaced four weeks apart. One session may include sham exposure in which the device is positioned identically but no therapeutic ultrasound energy is delivered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Adverse Events	Safety will be evaluated by assessing the incidence, severity, and relationship of adverse events associated with FUS neuromodulation.	From baseline (prior to first treatment) through 4 weeks after the second treatment, including assessments on the day of each treatment, 1 day, 1 week, and 2 weeks after each treatment, and at 4 weeks after the second treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Number of Drinking Days Using the Timeline Followback (TLFB)	The Timeline Followback (TLFB) is a validated calendar-based self-report method used to assess daily alcohol consumption over a defined period. Participants will report the number of standard drinks consumed each day over the previous 30 days. The total number of days on which alcohol was consumed will be calculated.	Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment
Change in Average Number of Drinks per Drinking Day Using TLFB	Participants' daily alcohol consumption over the previous 30 days will be assessed using the TLFB. The average number of standard drinks per drinking day will be calculated.	Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment
Change in Percent Days Abstinent Using TLFB	Using TLFB data, the percentage of days during the assessment period on which no alcohol was consumed will be calculated.	Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment
Change in Number of Heavy Drinking Days Using TLFB	Heavy drinking days will be defined as ≥5 drinks per day for men and ≥4 drinks per day for women. The number of such days over the assessment period will be calculated using TLFB data.	Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment
Subjective Ratings of Mood, Anxiety, Energy, and Optimism Using 1-9 Likert Scales	Participants will complete a brief set of self-reported Likert scales rating their current mood, anxiety, energy level, and optimism for the future. Each item is scored on a 1 to 9 scale, where: 1 = very low/poor 9 = very high/excellent These scales are used to capture rapid, subjective changes in well-being and affective state across the course of treatment.	Baseline, immediately before and after each treatment, 24 hours after each treatment, and 2 and 4 weeks after the second treatment
Change in Depressive Symptoms Using the Hamilton Depression Rating Scale (HAMD-17)	The HAMD-17 is a clinician-administered scale with 17 items measuring the severity of depressive symptoms. Total scores range from 0 to 52, with higher scores indicating more severe depression.	Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment
Change in anxiety symptoms using the Beck Anxiety Inventory (BAI)	Anxiety symptoms will be assessed using the Beck Anxiety Inventory (BAI), a 21-item self-report questionnaire. Each item is scored from 0 to 3, with a total score range of 0 to 63. Higher scores indicate greater anxiety symptom severity. Scores will be compared from baseline to post-treatment follow-up assessments.	Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment
Change in drug use severity using the Drug Use Disorders Identification Test (DUDIT)	Drug use severity will be assessed using the Drug Use Disorders Identification Test (DUDIT) in participants with drug-related substance use disorder, including stimulant, opioid, and/or ketamine use disorder. The DUDIT is an 11-item instrument used to assess drug-related problems. Items 1-9 are scored from 0 to 4, and items 10-11 are scored as 0, 2, or 4. The total score ranges from 0 to 44, with higher scores indicating greater drug use severity or greater likelihood of drug-related problems. Scores will be compared from baseline to post-treatment follow-up assessments.	Baseline, 3 months after the second treatment, and 6 months after the second treatment
Barratt Impulsiveness Scale (BIS-11)	The Barratt Impulsiveness Scale (BIS-11) is a widely utilized 30-item self-report instrument for assessing impulsivity. It is designed for the assessment of impulsivity in both research and clinical settings.	Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment
DSM-5 substance use disorders symptom checklist	11-item checklist based on behaviors over the past 12 months, classified as mild (2-3 symptoms), moderate (4-5), or severe (6+). Key symptoms include failed attempts to cut down, using more than intended, cravings, neglecting obligations, and continued use despite problems.	Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment.
The Colorado Symptom Index (CSI)	14-item, self-report questionnaire designed to measure the frequency of psychiatric symptoms (e.g., depression, anxity, psychosis) over the past month.	Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: August 8, 2025
• First Submitted That Met QC Criteria: July 2, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Neuromodulation; Focused Ultrasound (FUS); treatment-refractory substance use disorder
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders
• Other Study ID Numbers: 6703

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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