Substance Use Disorder (SUD)
Conditions
Keywords
Neuromodulation, Focused Ultrasound (FUS), treatment-refractory substance use disorder
Brief summary
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.
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.
Interventions
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.
Sponsors
Sunnybrook Health Sciences Centre
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Adverse Events | 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. | Safety will be evaluated by assessing the incidence, severity, and relationship of adverse events associated with FUS neuromodulation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Number of Drinking Days Using the Timeline Followback (TLFB) | Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment | 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. |
| Change in Average Number of Drinks per Drinking Day Using TLFB | Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment | 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. |
| Change in Percent Days Abstinent Using TLFB | Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment | Using TLFB data, the percentage of days during the assessment period on which no alcohol was consumed will be calculated. |
| Change in Number of Heavy Drinking Days Using TLFB | Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment | 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. |
| Subjective Ratings of Mood, Anxiety, Energy, and Optimism Using 1-9 Likert Scales | Baseline, immediately before and after each treatment, 24 hours after each treatment, and 2 and 4 weeks after the second treatment | 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. |
| Change in Depressive Symptoms Using the Hamilton Depression Rating Scale (HAMD-17) | Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment | 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. |
| Change in anxiety symptoms using the Beck Anxiety Inventory (BAI) | Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment | 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. |
| Change in drug use severity using the Drug Use Disorders Identification Test (DUDIT) | Baseline, 3 months after the second treatment, and 6 months after the second treatment | 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. |
| Barratt Impulsiveness Scale (BIS-11) | Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment | 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. |
| DSM-5 substance use disorders symptom checklist | Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment. | 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. |
| The Colorado Symptom Index (CSI) | Baseline, 2 weeks after the first treatment, and 2 and 4 weeks after the second treatment | 14-item, self-report questionnaire designed to measure the frequency of psychiatric symptoms (e.g., depression, anxity, psychosis) over the past month. |
Countries
Canada
Contacts
CONTACTNir Lipsman, MD, PhD, FRCSC
CONTACTAnusha Baskaran, PhD
Outcome results
None listed