Sonication-based OCD Neurosurgical Intervention Via Capsulotomy

NCT06131502 | Not Yet Recruiting Phase 1 DMC FDA Device

• 1 other identifier: 2025P003340
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to determine if ExAblate MR-guided Focused Ultrasound (MRgFUS) bilateral anterior capsulotomy can be used safely and effectively to relieve symptoms of moderate to severe obsessive compulsive disorder (OCD) in individuals who have not benefited from psychotherapy and medications. The main questions it aims to answer are:

1. 1.Can ExAblate MRgFUS capsulotomy be safely delivered to individuals suffering from treatment-refractory OCD through an intact skull with a risk and side-effect profile that is comparable to other neurosurgical approaches for capsulotomy?
2. 2.Will ExAblate MRgFUS capsulotomy result in improvement in clinical symptoms and quality of life metrics that are similar to those seen with other surgical approaches for capsulotomy?

Conditions

Obsessive-Compulsive Disorder

Keywords

OCD; neuroimaging; neurosurgery; MR-guided focused ultrasound (MRgFUS); Capsulotomy

Outcome Measures

Primary Outcomes (2)

• Phase I: Yale-Brown Obsessive-Compulsive Scale (YBOCS)

  Assesses the clinical severity of obsessive-compulsive symptoms (OCD). Higher scores indicate greater severity of OCD symptoms. Primary effectiveness will be evaluated using validated scores; the Y-BOCS score for the OCD patients, based upon patients where bilateral ExAblate capsulotomy was attempted (i.e., intent-to- treat analysis). Efficacy is defined as a reduction of 35% of pre-treatment Y-BOCS score at 12- months post-treatment.

  12 months

• Phase I: Evaluation of the incidence and severity of procedure related complications

  Subjective assessment of safety. The adverse event profile and improvement in Y-BOCS during the 6 months period of BMT will be compared to the adverse event profile and improvement in Y- BOCS during the next 12 months period of ExAblate MRgFUS capsulotomy plus BMT. Success is defined as at least 35% reduction in Y-BOCS in 33% of patients.

  12 months

Secondary Outcomes (7)

• Phase I: Clinical Global Impression (CGI) scale

  12 months

• Phase I: World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)

  12 months

• Phase I: Hamilton Rating Scale for Depression (HAM-D)

  12 months

• Phase I: Hamilton Rating Scale for Anxiety (HAM-A)

  12 months

• Phase I: Beck Depression Inventory (BDI)

  12 months

Other Outcomes (3)

• Phase I: Mini Mental State Examination (MMSE)

  12 months

• Phase I: Columbia Suicide Severity Rating Scale (C-SSRS)

  12 months

• Phase I: Neurological and Trauma Impairment Set Version 10 (NIS)

  12 months

Study Arms (2)

Active FUS

ACTIVE COMPARATOR

The treatment volume and plan will be defined by the neurosurgeon. The ExAblate MRgFUS system will automatically compute the number of sonications, and the (per sonication spot) phase and amplitude corrections necessary for the system to produce a focal spot at each of the desired locations. The target selected for this study is the anterior limb of the internal capsule (ALIC). The target will be approximately 7-10mm rostral to the anterior edge of the anterior commissure, in the ventral part of the ALIC. A central point in the targeted area will be targeted with a low dose, sub-lethal energy level sonication to confirm the targeting accuracy on the MR images. Focal point position and/or transducer location will be adjusted as necessary.

Device: ExAblate MR-guided Focused Ultrasound Bilateral Anterior Capsulotomy

Sham FUS

SHAM COMPARATOR

The sham procedure will be identical in planning and execution to the ExAblate procedure with the only exception being that the energy output will be 0 for the sham-treated subjects. To perform the sham treatment, the sonication will be performed with energy output disabled. For sham subjects, the physician will interact with a subject in a similar manner and for a similar duration to simulate an actual procedure. When possible, the treating physician may determine a sonication (treatment) time for sham subjects to be similar to that which is occurring in the ExAblate procedure to maintain consistency between treatment arms. It should be noted that all treatment times of both treatment arms will be captured in the study CRF.

Device: ExAblate MR-guided Focused Ultrasound Bilateral Anterior Capsulotomy

Interventions

ExAblate MR-guided Focused Ultrasound Bilateral Anterior Capsulotomy DEVICE

The ExAblate transcranial system combines a focused ultrasound surgery delivery system and a conventional diagnostic 3T MRI scanner. The ExAblate transcranial system provides real-time therapy planning algorithm, thermal dosimetry, and closed-loop therapy control.

Active FUS; Sham FUS

Eligibility Criteria

• Age: 25 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• years, inclusive.
• Patients who are able and willing to give consent and able to attend study visits, as determined by both study psychiatrist and the surgeon.
• DSM-5 diagnosis of Obsessive-Compulsive Disorder (OCD), at least 5-year illness history, with a minimum score of 28 on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for stage I and a minimum score of 24 on Y-BOCS for stage II.
• Medication-refractoriness as determined by an adequate dose and duration of standard psychiatric treatments (including psychotherapy and/or pharmacology) as determined by psychiatrists associated with the study. Including specifically:
• Failed adequate trial of three or more medications accepted as first line in the treatment of OCD such as selective serotonin reuptake inhibitors (SSRIs, e.g. fluoxetine, citalopram), selective serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs, e.g. clomipramine) or other antidepressants at the maximal tolerated dose. Adequate maximal doses and minimal duration of these medication are listed in Table 2 below.
• Attempted augmentation, if tolerated, by at least two medications known to be second line treatments for OCD such as clonazepam, haloperidol, risperidone, olanzapine, gabapentin.
• An adequate trial of cognitive behavioral therapy (CBT) delivered by a therapist experienced in treating OCD. Criteria for an adequate CBT are listed in Table 3 below.
• In stage II patients that cannot tolerate pharmacotherapy or participate in psychotherapy will be included in the study.
• A consistent dose of all medications in the 30 days prior to study entry
• Able to communicate sensations during the ExAblate MRgFUS treatment

You may not qualify if:

• Presence of significant cognitive impairment (as measured by a score \<25 on the mini-mental state examination, MMSE)
• Lifetime diagnosis of psychosis or bipolar disorder or presence of suicidality (as measured by a score \>=2, item 9 of the BDI or high suicidal risk measured by the Columbia Suicide Severity Rating Scale (C-SSRS)). Subjects with stable, chronic anxiety or depressive disorders may be included provided their medications have been stable for at least 3 months prior to study entry and if deemed appropriately managed by the site psychiatrist.
• DSM-5 diagnosis of substance use disorder (SUD) within the past 6 months
• Patients with unstable cardiac status \[e.g. unstable angina pectoris on medication; patients' medication (other than diuretic); patients on anti-arrhythmic drugs; severe hypertension (diastolic BP \> 100 on medication)\]
• Cerebrovascular disease (e.g. CVA within 6 months), history of intracranial hemorrhage or intracranial aneurysms requiring treatment or arterial venous malformations (AVMs) requiring treatment
• Untreated, uncontrolled sleep apnea
• Patients with brain tumors, epilepsy, neurodegenerative disease or any other major neurological disorder
• Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
• Known intolerance or allergies to MRI contrast agent (e.g. Gadolinium or Magnevist) including advanced kidney disease
• Subjects who weigh more than the upper weight limit of the MR scanner table and who cannot fit into the MR scanner
• An Overall Skull Density Ratio of less than 0.40 as calculated from the screening CT
• Severely impaired renal function (estimated glomerular filtration rate \< 30ml/min/1.73 m2) or receiving dialysis
• Laboratory biochemical evidence of abnormal bleeding and/or coagulopathy, including risk factors for intraoperative or postoperative bleeding (platelet count less than 100,000 per cubic millimeter or abnormal INR)
• Current medical condition resulting in abnormal bleeding and/or coagulopathy.
• Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk of hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure. Receiving medications or supplements that increase the risk of bleeding such as NSAIDS, Ginko Baloba and Ginseng within one week of focused ultrasound procedure.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Stanford University: collaborator

Study Sites (2)

Stanford University

Palo Alto, California, 94305, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: In the first stage, patients will not be randomized and neither patients nor evaluators will be blinded as to treatment status. A period of 6 months of best medical treatment (BMT) prior to the capsulotomy treatment will ensure that the patients are clinically stable and compliant with the study set-up. If no safety stop rules occur at the end of the first stage, we will submit an IDE supplement to the FDA providing evidence of safety and requesting continuation. The second stage would then proceed pending the receipt and review/approval of that supplement. The second stage is focused on efficacy. In stage II, patients will be randomized, and both patient and evaluators will be blinded as to treatment status. The patients will be treated by BMT plus MRgFUS or BMT plus sham for 12 months. Parallel BMT along with the sham and MRgFUS periods would decrease protocol violations or drop-outs.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: In the first stage of the study, participants with severe, treatment resistant OCD (n=10) will be recruited in two centers (Harvard and Stanford) and treated with best medical care (BMT) for 6 months. Thereafter, they will receive the ExAblate MRgFUS procedure and then another BMT for 12 months. In the second stage of the study, participants with moderate to severe OCD (n=56) will be recruited in a multi-center study and treated with BMT plus real or sham MRgFUS for 12 months. Thereafter, those who received sham MRgFUS and did not improve will receive real MRgFUS and then treated with BMT for another 12 months.

Study Record Dates

• First Submitted: November 9, 2023
• First Posted: November 14, 2023
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2032
• Last Updated: February 25, 2026

Record last verified: 2025-10

Locations

US (2)