<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03244852</url>
  </required_header>
  <id_info>
    <org_study_id>2017P000882</org_study_id>
    <nct_id>NCT03244852</nct_id>
  </id_info>
  <brief_title>Patient-specific, Effective, and Rational Functional Connectivity Targeting for DBS in OCD</brief_title>
  <acronym>PERFECT DBS</acronym>
  <official_title>Patient-specific, Effective, and Rational Functional Connectivity Targeting for DBS in OCD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study aims to improve patient-specific anatomical targeting of the Deep Brain Stimulation&#xD;
      for the treatment of intractable OCD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recently, deep brain stimulation (DBS) has emerged as a potentially circuit-specific&#xD;
      treatment for intractable OCD. DBS is programmable, allowing the clinician to &quot;reshape&quot; the&#xD;
      volume of tissue activated within the standard ventral capsule/ventral striatum (VC/VS)&#xD;
      target.&#xD;
&#xD;
      However, VC/VS DBS' efficacy is limited by two major factors: imperfect targeting and a lack&#xD;
      of decision rules for stimulation adjustment. The VC/VS target is not a single identifiable&#xD;
      structure, but encompasses white matter of the internal capsule and gray matter of the&#xD;
      nucleus accumbens (NAc). In current practice for DBS in OCD, all patients are implanted at&#xD;
      standard x,y,z coordinates in the VC/VS region. Due to this inter-subject anatomical&#xD;
      variability, different fiber tracts are stimulated by ostensibly the &quot;same&quot; parameters in&#xD;
      each subject, leading to variable outcomes. This investigation will identify aspects of VC/VS&#xD;
      circuitry that may determine clinical response. The hypothesis is that good clinical outcomes&#xD;
      may correlate to electrical field capture of either striatal gray matter or of white matter&#xD;
      fibers connecting OFC to thalamus.&#xD;
&#xD;
      The current study looks to extend the neuroimaging investigation using anatomic white matter&#xD;
      targeting, functional gray matter targeting and changes in changes in regional glucose&#xD;
      metabolism of Deep Brain Stimulation (DBS) in severe obsessive-compulsive disorder (OCD) with&#xD;
      the long-term aim of identifying biomarkers that could improve outcomes of this expensive and&#xD;
      invasive therapy. Improved imaging would allow surgeons to place the DBS lead closer to the&#xD;
      biological targets, thus improving efficacy of the treatment.&#xD;
&#xD;
      The objectives of this study are threefold:&#xD;
&#xD;
        -  Improve the anatomic white matter targeting of the Deep Brain Stimulator (DBS) implant&#xD;
           by tracing and identifying fibers of passage within the Ventral Capsule (VC) white&#xD;
           matter using advance tractography methods in preoperative diffusion MRI data.&#xD;
&#xD;
        -  Improve functional gray matter targeting by studying the overlap of the volume of tissue&#xD;
           activated (VTA) with the VC voxels of maximal preoperative connectivity to the&#xD;
           orbitofrontal cortex (OFC)&#xD;
&#xD;
        -  Determine the changes in regional glucose metabolism using preoperative and&#xD;
           post-treatment FDG-PET (Positron Emission Tomography) following 3 months of DBS&#xD;
           treatment&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Data was analyzed from a previously collected dataset so no new participants were enrolled.&#xD;
  </why_stopped>
  <start_date type="Actual">September 15, 2017</start_date>
  <completion_date type="Actual">January 31, 2022</completion_date>
  <primary_completion_date type="Actual">January 31, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Yale-Brown Obsessive-Compulsive Scale (YBOCS)</measure>
    <time_frame>6 months</time_frame>
    <description>Yale-Brown Obsessive-Compulsive Scale (YBOCS) will be the principal outcome measure to correlate OCD symptoms severity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Neural Correlates (1)</measure>
    <time_frame>6 months</time_frame>
    <description>Clinical improvement (change in YBOCS from baseline) will be correlated with the degree of postoperative capture of OFC fibers in the VTA of the active DBS contact</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Neural Correlates (2)</measure>
    <time_frame>6 months</time_frame>
    <description>Clinical improvement (change in YBOCS from baseline) will be correlated with overlap of the volume of tissue activated (VTA) with the identified ventral striatum voxels of maximal preoperative connectivity to the OFC.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Neural Correlates (3)</measure>
    <time_frame>6 months</time_frame>
    <description>Clinical improvement (change in YBOCS from baseline) will be correlated with changes in regional glucose metabolism in the OFC, caudate, and thalamus.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">0</enrollment>
  <condition>Obsessive-Compulsive Disorder</condition>
  <arm_group>
    <arm_group_label>OCD Patients with Deep Brain Stimulators</arm_group_label>
    <description>Patients with deep brain stimulation for intractable obsessive compulsive disorder (OCD)</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Subjects will be 11 patients with DSM-5-defined OCD of disabling severity, refractory to&#xD;
        prolonged treatment trials with conventional medication and behavioral therapy, who would&#xD;
        therefore otherwise be candidates for psychiatric neurosurgery.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. OCD, diagnosed by Structured Clinical Interview for DSM-5 (SCID-5), judged of&#xD;
             disabling severity with a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of at&#xD;
             least 28.&#xD;
&#xD;
          2. Persistence of severe symptoms and impairment for five or more years despite: i. at&#xD;
             least three adequate (≥3 months at the maximum tolerated dose) serotonin transporter&#xD;
             inhibitor trials (may use any serotonin or serotonin-norepinephrine inhibitors, but&#xD;
             must include a trial of clomipramine) alone or in combination with ii. adequate&#xD;
             behavior therapy (≥20 sessions of expert exposure and response prevention; At least 20&#xD;
             sessions of behavioral therapy must be attempted), and iii. augmentation of one of the&#xD;
             selective SRIs with a neuroleptic or clonazepam.&#xD;
&#xD;
          3. Age between 21 and 64 years.&#xD;
&#xD;
          4. Able to understand and comply with instructions.&#xD;
&#xD;
          5. Able to give fully informed, written consent.&#xD;
&#xD;
          6. Approved to be implanted with a DBS device for OCD.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Current or past psychotic disorder.&#xD;
&#xD;
          2. Full-scale IQ below 75 on the Wechsler Abbreviated Scale of Intelligence (WAIS) or&#xD;
             cognitive impairment that would affect a participant's ability to give informed&#xD;
             consent or provide interview or self-report data reliably, as determined by the&#xD;
             consent monitor and the site psychiatrist. A questionnaire assessing consent&#xD;
             comprehension will be used with all study subjects, to ensure that they understand the&#xD;
             key procedures of the study, and its risks and benefits.&#xD;
&#xD;
          3. A clinical history of bipolar mood disorder; substance-induced mania is not an&#xD;
             exclusion.&#xD;
&#xD;
          4. Any current clinically significant neurological disorder or medical illness affecting&#xD;
             brain function, other than tic disorders or Tourette syndrome.&#xD;
&#xD;
          5. Any clinically significant abnormality on preoperative magnetic resonance imaging&#xD;
             (MRI).&#xD;
&#xD;
          6. Any labeled DBS contraindication, and/or inability to undergo presurgical MRI (cardiac&#xD;
             pacemaker, pregnancy, metal in body, severe claustrophobia), infection, coagulopathy,&#xD;
             inability to undergo an awake operation, significant cardiac or other medical risk&#xD;
             factors for surgery.&#xD;
&#xD;
          7. Current or unstably remitted substance abuse, dependence, or a positive urine&#xD;
             toxicology screen.&#xD;
&#xD;
          8. Pregnancy and women of childbearing age not using effective contraception.&#xD;
&#xD;
          9. Unable to adhere to operational and administrative study requirements (in the&#xD;
             investigators' judgment).&#xD;
&#xD;
         10. Clinical history of severe personality disorder.&#xD;
&#xD;
         11. Imminent risk of suicide or an inability to control suicide attempts (in the&#xD;
             investigators' judgment). History of serious suicidal behavior or one or more&#xD;
             interrupted suicide attempts with potential lethality judged to result in serious&#xD;
             injury or death.&#xD;
&#xD;
         12. Diagnosis of body dysmorphic disorder.&#xD;
&#xD;
         13. Evidence of dementia or other significant cognitive impairment on neuropsychological&#xD;
             evaluation&#xD;
&#xD;
         14. Past or present diagnosis of hoarding disorder.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Darin D Dougherty, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Charlestown</city>
        <state>Massachusetts</state>
        <zip>02129</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>June 26, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <last_update_submitted>May 12, 2022</last_update_submitted>
  <last_update_submitted_qc>May 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Darin Dougherty, MD</investigator_full_name>
    <investigator_title>Director, Division of Neurotherapeutics</investigator_title>
  </responsible_party>
  <keyword>OCD</keyword>
  <keyword>deep brain stimulation</keyword>
  <keyword>treatment-resistant OCD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obsessive-Compulsive Disorder</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03244852
org study id: 2017P000882
nct id: NCT03244852
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The study aims to improve patient-specific anatomical targeting of the Deep Brain Stimulation
      for the treatment of intractable OCD.
Recently, deep brain stimulation (DBS) has emerged as a potentially circuit-specific
      treatment for intractable OCD. DBS is programmable, allowing the clinician to "reshape" the
      volume of tissue activated within the standard ventral capsule/ventral striatum (VC/VS)
      target.

      However, VC/VS DBS' efficacy is limited by two major factors: imperfect targeting and a lack
      of decision rules for stimulation adjustment. The VC/VS target is not a single identifiable
      structure, but encompasses white matter of the internal capsule and gray matter of the
      nucleus accumbens (NAc). In current practice for DBS in OCD, all patients are implanted at
      standard x,y,z coordinates in the VC/VS region. Due to this inter-subject anatomical
      variability, different fiber tracts are stimulated by ostensibly the "same" parameters in
      each subject, leading to variable outcomes. This investigation will identify aspects of VC/VS
      circuitry that may determine clinical response. The hypothesis is that good clinical outcomes
      may correlate to electrical field capture of either striatal gray matter or of white matter
      fibers connecting OFC to thalamus.

      The current study looks to extend the neuroimaging investigation using anatomic white matter
      targeting, functional gray matter targeting and changes in changes in regional glucose
      metabolism of Deep Brain Stimulation (DBS) in severe obsessive-compulsive disorder (OCD) with
      the long-term aim of identifying biomarkers that could improve outcomes of this expensive and
      invasive therapy. Improved imaging would allow surgeons to place the DBS lead closer to the
      biological targets, thus improving efficacy of the treatment.

      The objectives of this study are threefold:

        -  Improve the anatomic white matter targeting of the Deep Brain Stimulator (DBS) implant
           by tracing and identifying fibers of passage within the Ventral Capsule (VC) white
           matter using advance tractography methods in preoperative diffusion MRI data.

        -  Improve functional gray matter targeting by studying the overlap of the volume of tissue
           activated (VTA) with the VC voxels of maximal preoperative connectivity to the
           orbitofrontal cortex (OFC)

        -  Determine the changes in regional glucose metabolism using preoperative and
           post-treatment FDG-PET (Positron Emission Tomography) following 3 months of DBS
           treatment
observational model: Cohort
time perspective: Retrospective
measure: Yale-Brown Obsessive-Compulsive Scale (YBOCS)
time frame: 6 months
description: Yale-Brown Obsessive-Compulsive Scale (YBOCS) will be the principal outcome measure to correlate OCD symptoms severity.
measure: Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Neural Correlates (1)
time frame: 6 months
description: Clinical improvement (change in YBOCS from baseline) will be correlated with the degree of postoperative capture of OFC fibers in the VTA of the active DBS contact
measure: Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Neural Correlates (2)
time frame: 6 months
description: Clinical improvement (change in YBOCS from baseline) will be correlated with overlap of the volume of tissue activated (VTA) with the identified ventral striatum voxels of maximal preoperative connectivity to the OFC.
measure: Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Neural Correlates (3)
time frame: 6 months
description: Clinical improvement (change in YBOCS from baseline) will be correlated with changes in regional glucose metabolism in the OFC, caudate, and thalamus.
arm group label: OCD Patients with Deep Brain Stimulators
description: Patients with deep brain stimulation for intractable obsessive compulsive disorder (OCD)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 21 Years
maximum age: 64 Years
healthy volunteers: No
last name: Darin D Dougherty, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Darin Dougherty, MD
investigator title: Director, Division of Neurotherapeutics
mesh term: Obsessive-Compulsive Disorder
sharing ipd: No