Ventral Capsulotomy for Intractable OCD

Cognition and Magnetic Resonance Imaging After Psychiatric Neurosurgery for Intractable Obsessive-Compulsive Disorder- Phase 2

Obsessive-compulsive disorder impacts 1-2 percent of the population. Unfortunately, about fifteen percent of patients fail to benefit from existing therapies. A small number of OCD patients, who have a disabling illness that does not improve after conventional treatments, have neurosurgery as a last resort. One procedure, capsulotomy, involves making pairs of lesions in an anatomically-defined part of the anterior limb of the internal capsule, a structure containing nerve fiber bundles connecting the thalamus, in the center of the brain, to the prefrontal cortex, the most anterior and outermost brain region. The investigators will examine how the therapeutic effects of capsulotomy relate to changes in the structure of these brain pathways with structural (diffusion tensor imaging, DTI) and functional (resting-state and task-based) connectivity metrics. The investigators will also utilize experimental cognitive tasks that are sensitive to the circuitry impacted by this procedure.

Study Overview

• Status: Enrolling by invitation
• Conditions: Obsessive-Compulsive Disorder
• Intervention / Treatment: Device: Laser Interstitial Thermal Therapy

Detailed Description

Obsessive-compulsive disorder (OCD) is a common condition. One to two percent of the population experiences the chronic intrusive obsessive thoughts, repetitive compulsions, and pathological anxiety characteristic of the illness, which by several measures is among the ten most disabling medical conditions for adults in industrialized countries. Unfortunately, about fifteen percent of patients fail to benefit from existing therapies. A small number of OCD patients, who have a disabling illness that does not improve after conventional treatments, have neurosurgery as a last resort. One procedure, capsulotomy, involves making pairs of lesions in an anatomically-defined part of the anterior limb of the internal capsule, a structure containing nerve fiber bundles connecting the thalamus, in the center of the brain, to the prefrontal cortex, the most anterior and outermost brain region. OCD is believed to result from abnormal activity in brain circuits connecting the prefrontal cortex, thalamus and other brain areas. Data show that approximately 50 to 60 percent of patients improve after capsulotomy.

In addition, new neuroimaging measures of how brain fiber tracts and the brain regions associated with them change after capsulotomy promise to enhance the understanding of OCD pathophysiology, and may help advance capsulotomy and other neuroanatomically-based therapies. While capsulotomy is believed to exert its therapeutics effects by changing thalamus-prefrontal cortex connections, the specific anatomical changes produced by this surgical treatment in these fiber pathways are unknown. This is especially true at greater distances from the site of surgery, that is, closer to the thalamus and prefrontal cortex, the regions the surgery is intended to partially disconnect from each other. The investigators will examine how the therapeutic effects of capsulotomy relate to changes in the structure of these brain pathways with structural (diffusion tensor imaging, DTI) and functional (resting-state and task-based) connectivity metrics. Additional measures of how brain volumes may change in specific corticobasal structures implicated in OCD (including the basal ganglia, thalamus, and orbitofrontal cortex) will be derived from conventional MRI measures obtained during the same sessions when the experimental DT-MRI measures are acquired. The investigators will also utilize experimental cognitive tasks that are sensitive to the circuitry impacted by this procedure.

Understanding the changes after surgery that result in the best therapeutic outcomes will allow the investigators to improve capsulotomy as a treatment for this debilitating disease. With this information, the investigators can refine the targeting of capsulotomy for individual patients and, possibly, aid the development of other treatments, including deep brain stimulation, for intractable OCD. This study provides a unique opportunity to test structural and functional connectivity measures as probes of complex neuronal circuits that are likely to be involved in psychiatric illness.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Study Population

Patients will be adults with severe, intractable OCD who have received approval for a clinical capsulotomy procedure through the Butler Hospital Psychiatric Neurosurgery Committee

Description

Inclusion Criteria:

• Patients who will be undergoing capsulotomy for severe OCD, as approved by the Butler Hospital Psychiatric Neurosurgery Committee

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yale-Brown Obsessive-Compulsive Scale (YBOCS)	Change from baseline to 12 months on YBOCS score; YBOCS score ranges from 0-40, and higher scores indicate more severe illness	12 months
Yale-Brown Obsessive-Compulsive Scale (YBOCS)	Change from baseline to 24 months on YBOCS score; YBOCS score ranges from 0-40, and higher scores indicate more severe illness	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Rating Scale (HDRS)	Change from baseline to 12 months on HDRS score; HRDS scores range from 0-52, with higher scores indicating more severe illness	12 months
Hamilton Anxiety Rating Scale (HARS)	Change from baseline to 12 months on HARS score; HARS score ranges from 0-56, with higher scores indicating more severe illness	12 months

Collaborators and Investigators

• Sponsor: Butler Hospital
• Collaborators: National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2022
• Primary Completion (Anticipated): December 31, 2032
• Study Completion (Anticipated): December 31, 2032

Study Registration Dates

• First Submitted: December 5, 2022
• First Submitted That Met QC Criteria: December 12, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 25, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Personality Disorders; Anxiety Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder
• Other Study ID Numbers: 1909-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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