Deep Brain Stimulation of the Anterior Cingulate Bundle (ACB) and the Ventral Anterior Limb of the Internal Capsule (vALIC) in Patients With Intractable Obsessive Compulsive Disorder (OCD)

Official title

Double-Blind, Crossover, Feasibility Study of Deep Brain Stimulation of the Anterior Cingulate Bundle (ACB) and the Ventral Anterior Limb of the Internal Capsule (vALIC) in Patients With Intractable Obsessive Compulsive Disorder (OCD)

Overview

This is a double blind pilot feasibility study, with a within subject crossover design of DBS of the anterior cingulate bundle(ACB) and the ventral anterior limb of the internal capsule(vALIC) in four patients with intractable OCD. Patients will be screened according to inclusion exclusion criteria listed above, approved by an independent Neuropsychiatric review board and informed consent obtained.

Detailed description

This is a double blind pilot feasibility study, with a within subject crossover design of DBS of the anterior cingulate bundle(ACB) and the ventral anterior limb of the internal capsule(vALIC) in four patients with intractable OCD. Patients will be screened according to inclusion exclusion criteria listed above, approved by an independent Neuropsychiatric review board and informed consent obtained. Following implantation of bilateral Medtronic Percept stimulating and recording electrodes in the ACB with electrode Medtronic 3391 and of bilateral Medtronic 3387 electrodes in participants, they will be entered into a two week baseline period with baseline clinical assessments(see Schedule of Assessments) and imaging. Patients will be randomized into ACB or vALIC arms of the study and enter a two week period of stimulation optimization followed by 12 weeks of active blinded treatment in the first condition and then crossed over to the alternate condition where following discontinuation of the first condition stimulation an additional two week period of stimulation optimization in the alternate condition will be followed by an additional twelve weeks of stimulation in the alternate condition. Primary outcome measures will include the YBOCs-II and the Clinical Global Assessment. Ratings will be obtained by independent raters blind to stimulation condition. Following the completion of the second 12 week blinded period, the patient will enter an open nonblinded study of ACB plus vALIC stimulation.

Interventions

• Device Medtronic Percept system and 3391 3387 Medtronic DBS electrodes
  Surgical implantation of deep brain stimulation electrodes with stimulation at one of two intracranial targets depending on randomization and crossover status.

Primary outcome measures

• Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) [Time frame: At the final visit of Stage 1, which occurs at the end of 12 weeks of active stimulation of the first target.]
• Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) [Time frame: At the final visit of Stage 2, which occurs at the end of 12 weeks of active stimulation of the second target.]
• Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) [Time frame: At the final visit of Stage 3, which occurs at the end of 12 weeks of active stimulation of both targets.]
• Clinical Global Impression (CGI) [Time frame: At the final visit of Stage 1, which occurs at the end of 12 weeks of active stimulation of the first target.]
• Clinical Global Impression (CGI) [Time frame: At the final visit of Stage 2, which occurs at the end of 12 weeks of active stimulation of the second target.]
• Clinical Global Impression (CGI) [Time frame: At the final visit of Stage 3, which occurs at the end of 12 weeks of active stimulation of both targets.]

Secondary outcome measures (6)

• Global Assessment of Functioning (GAF) [Time frame: At the final visit of Stage 1, which occurs at the end of 12 weeks of active stimulation of the first target.]
• Global Assessment of Functioning (GAF) [Time frame: At the final visit of Stage 2, which occurs at the end of 12 weeks of active stimulation of the second target.]
• Global Assessment of Functioning (GAF) [Time frame: At the final visit of Stage 3, which occurs at the end of 12 weeks of active stimulation of the both targets.]
• Sheehan Disability Scale (SDS) [Time frame: At the final visit of Stage 1, which occurs at the end of 12 weeks of active stimulation of the first target.]
• Sheehan Disability Scale (SDS) [Time frame: At the final visit of Stage 2, which occurs at the end of 12 weeks of active stimulation of the second target.]
• Sheehan Disability Scale (SDS) [Time frame: At the final visit of Stage 3, which occurs at the end of 12 weeks of active stimulation of both targets.]

Eligibility criteria

Inclusion criteria

• OCD, diagnosed by Structured Clinical Interview for DSM-IV (SCID-IV), judged of disabling severity with a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of at least 30 and a Global Assessment of Functioning (GAF) score of 45 or less.
• Persistence of severe symptoms and impairment for five or more years despite at least three adequate (≥3 months at the maximum tolerated dose) serotonin transporter inhibitor trials (fluoxetine, sertraline, fluvoxamine, paroxetine, citalopram, escitalopram, or clomipramine) alone or in combination with ii. Adequate behavior therapy (≥20 sessions of expert exposure and response prevention), and iii. Augmentation of one of the selective SRIs with clomipramine, a neuroleptic, and clonazepam.
• Age between 21 and 65 years.
• Able to understand and comply with instructions.
• Able to give fully informed, written consent in the judgment of the site Consent Monitor.
• Either drug free or on a stable drug regimen for at least 6 weeks.
• Good general health.
• A family member or significant other, in contact with the patient every 1-3 days, is available and willing to communicate with the research team if the patient's clinical status worsens, and if necessary to accompany patients to study visits.
• The local referring psychiatrist is willing to provide ongoing care during and after the trial

Exclusion criteria

• personal/family history (1st/2nd degree relatives) of schizophrenia or schizoaffective disorder, other primary psychotic disorder, bipolar disorder;
• present PTS;
• present acute suicidality or suicidal ideation;
• personal history of head injury, epilepsy, tic or other neurological disorders, neurodevelopmental (e.g., autism), systemic medical (metabolic, endocrine, chronic inflammatory, vascular, autoimmune) disease from medical records and self-report (all of which may confound interpretation of neuroimaging measures);
• MMSE score < 24;
• premorbid IQ estimate < 85;
• visual disturbance (<20/40 Snellen visual acuity, corrected);
• left/mixed handedness;
• current, or alcohol or illicit substance abuse/dependence in the last 3 months, determined by clinical assessment and urine toxicology;
• contraindications to MRI,: metallic foreign objects, e.g., aneurysm clips/pacemakers, or questionable history of metal fragments, claustrophobia raising the risk of panicking in enclosed spaces;
• positive pregnancy test for women of reproductive age, or women not using medically acceptable birth control throughout the study (barrier and/or oral contraceptives);
• current psychotic symptoms (potential confounding effect on neuroimaging measures; see above);
• an increased risk of seizure, determined by history;

4\) potentially proconvulsant medications (e.g., bupropion, tricyclic antidepressants, first-generation antipsychotics, lithium), and medications reducing cortical excitability (e.g., anticonvulsants, benzodiazepines, atypical antipsychotics).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07303946 · 5POMH106435P52

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗