Focused ultrasound neuromodulation for treatment-resistant depression

Assessment of Safety and Feasibility of Focused Ultrasound Next Generation Dome Helmet (NGDH) to Perform Neuromodulation in Patients With Treatment-Resistant Depression

This trial will test whether MRI-guided focused ultrasound using the Next Generation Dome Helmet can safely reduce depressive symptoms in adults whose depression has not improved with standard treatments.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Sunnybrook Health Sciences Centre (Academic / other)
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT07094789 on ClinicalTrials.gov

What this trial studies

This is a prospective, single-arm, non-randomized pilot enrolling 20 adults with treatment-resistant major depressive disorder. Participants will receive two MRI-guided focused ultrasound neuromodulation sessions targeting nodes of the cortical-striatal-thalamic circuit, spaced four weeks apart, using the Next Generation Dome Helmet (NGDH). Safety and initial clinical effects will be monitored with clinical rating scales and imaging at 24 hours, 2 weeks, and 4 weeks after each treatment session. Eligibility requires DSM-5 MDD, HAMD-17 >20, stable medications, prior trials of at least two antidepressants and prior psychotherapy; treatments and follow-up occur at Sunnybrook Health Sciences Centre in Toronto.

Who should consider this trial

Good fit: Adults 18–65 with DSM-5 major depressive disorder, a HAMD-17 score over 20, stable psychiatric medications, and documented failure of at least two adequate antidepressant trials plus prior psychotherapy are ideal candidates.

Not a fit: People who are pregnant, have moderate-or-worse substance use disorders (aside from cannabis or nicotine), active seizure disorder, significant imaging-verified head injury, or other exclusionary medical conditions may not benefit or be eligible.

Why it matters

Potential benefit: If successful, this could provide a noninvasive treatment option that lessens depressive symptoms in people who have not responded to standard therapies.

How similar studies have performed: MR-guided focused ultrasound neuromodulation is an emerging, early-stage approach with small pilot studies showing mixed but encouraging signals, so it remains largely experimental for treatment-resistant depression.

Eligibility criteria

Inclusion Criteria:

1. Deemed to have the capacity to provide informed consent.
2. Aged between 18 and 65 years.
3. Diagnosis of major depressive disorder (MDD) according to DSM-5 criteria.
4. Total score \>20 on the Hamilton Depression Rating Scale (HAMD-17).
5. On a stable regimen of psychiatric medications for at least 30 days prior to enrollment.
6. Documented previous trial of at least two first-line antidepressant agents at adequate dose and duration, as assessed by two psychiatrists.
7. Documented previous trial of cognitive behavioral therapy (CBT) or psychotherapy for MDD, sustained for at least 6 weeks.

Exclusion Criteria:

1. Pregnant or intending to become pregnant during the study period.
2. Diagnosis of a substance use disorder (excluding cannabis or nicotine) of moderate severity or greater, or when the substance is the primary focus of treatment, based on DSM-5 criteria.
3. Known active seizure disorder, significant head injury with an imaging-verified lesion
4. Unstable medical illness.
5. Not eligible for 3-Tesla MRI (i.e. MRI-incompatible pacemaker)
6. Inability to reliably attend required screening, treatment, or follow-up appointments.
7. Severe claustrophobia, as identified by the participant, that would prevent completion of MRI procedures.

Where this trial is running

Toronto, Ontario

• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Study coordinator: Nir Lipsman, MD, PhD, FRCSC

Conditions Treatment-Resistant Depression; Treatment-resistant Depression; Neuromodulation; Focused Ultrasound; FUS; TRD; CSTC Circuit