Focused Ultrasound Neuromodulation in Patients With Treatment-Resistant Depression

Sunnybrook Health Sciences Centre20 enrolled

Overview

The goal of this clinical trial is to evaluate the safety and initial effectiveness of Magnetic Resonance-guided focused ultrasound neuromodulation using the Next Generation Dome Helmet (NGDH) device in patients with treatment-resistant depression. This is a prospective, single-arm, non-randomized study. Participants will: * Undergo two focused ultrasound treatment sessions targeting nodes of the cortical-striatal-thalamic circuit (CSTC) , spaced four weeks apart. * Return for follow-up visits at 24 hours, 2 weeks, and 4 weeks after each treatment session, during which clinical scales and imaging assessments will be conducted to monitor safety and clinical effects.

A total of 20 participants with treatment-resistant depression will be enrolled and treated in this study. Participants will be recruited through local psychiatric practices, referrals from participating institutions, and external referrals, including both physician and self-referrals. Eligibility will be assessed during a dedicated screening appointment conducted by the study coordinator in collaboration with a study-affiliated physician. The anticipated enrollment period is approximately two years, beginning from the date of first patient enrollment to the enrollment of the final participant.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Treatment-Resistant Depression

Interventions

Next Generation Dome Helmet (NGDH)DEVICE

Participants will receive two sessions of Magnetic Resonance-guided focused ultrasound neuromodulation, spaced four weeks apart, using the Next Generation Dome Helmet device. Treatments will target regions within the CSTC circuit identified by advanced MRI scans. Each session will include pre-treatment assessments, precise sonications of deep brain structures, real-time safety monitoring, and post-treatment imaging.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Safety and Feasibility of FUS Next Generation Dome Helmet (NGDH) to Perform Neuromodulation in Patients with Treatment-Resistant Depression

Assessment of the frequency and severity of adverse events associated with focused ultrasound neuromodulation in patients with treatment-resistant depression using the Next Generation Dome Helmet device. Adverse events, including procedure-related complications and neurological events, will be documented and assessed throughout the study period.

Time frame: Assessments will be conducted at the baseline visit, 24 hours after the first treatment, 2 weeks after the first treatment, 24 hours after the second treatment, and at 2 and 4 weeks following the second treatment.

Secondary Outcomes

Clinical Efficacy - Change in Depressive Symptoms measured by Hamilton Depression Rating Scale (HAMD-17)

Clinical efficacy will be evaluated by analyzing changes in symptom scores using repeated-measures analysis of variance. The primary measure of clinical efficacy will be the Hamilton Depression Rating Scale (HAMD-17) score.

Time frame: Assessed at 2 weeks after first treatment and 2 and 4 weeks after second treatment.