Clinical trial NCT05659082: Ventral Capsulotomy for Intractable OCD
Official title: Cognition and Magnetic Resonance Imaging After Psychiatric Neurosurgery for Intractable Obsessive-Compulsive Disorder- Phase 2
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Obsessive-Compulsive Disorder
Lead sponsor: Butler Hospital
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2022-12-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

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

Primary outcomes:
measure: Yale-Brown Obsessive-Compulsive Scale (YBOCS)
timeFrame: 12 months
measure: Yale-Brown Obsessive-Compulsive Scale (YBOCS)
timeFrame: 24 months
Secondary outcomes:
measure: Hamilton Depression Rating Scale (HDRS)
timeFrame: 12 months
measure: Hamilton Anxiety Rating Scale (HARS)
timeFrame: 12 months
Other outcomes:
Locations:
city: Providence
country: United States
facility: Butler Hospital
state: Rhode Island
Study officials:
References: