<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/NCT01725334</url>
  </required_header>
  <id_info>
    <org_study_id>078/2011</org_study_id>
    <nct_id>NCT01725334</nct_id>
  </id_info>
  <brief_title>Deep Brain Stimulation (DBS) for the Management of Treatment Refractory Negative Symptoms in Schizophrenia</brief_title>
  <official_title>Deep Brain Stimulation for the Management of Treatment Refractory Negative Symptoms in Schizophrenia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre for Addiction and Mental Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Schizophrenia Society of Ontario</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre for Addiction and Mental Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Schizophrenia is a complex, challenging, and heterogeneous psychiatric condition, affecting&#xD;
      up to 0.5% of the population and responsible for nearly 2% of all Canadian health-care&#xD;
      expenditure. Much of the morbidity of the illness is related to its negative symptoms,&#xD;
      including amotivation, asociality, anhedonia and flattened emotional affect, which lead to&#xD;
      functional impairment and withdrawal from social and occupational domains. In contrast to&#xD;
      positive symptoms, such as hallucinations and delusions, there are currently no effective&#xD;
      treatments for negative symptoms, which experts recognize are largely responsible for the&#xD;
      long-term disability of a majority of patients with schizophrenia. Advances in neuroscience&#xD;
      have allowed a greater understanding of negative symptoms and have identified key structures&#xD;
      and circuits believed to generate and maintain them. Here, we propose the application of a&#xD;
      targeted therapy, deep brain stimulation, to alter the circuits driving negative symptoms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Schizophrenia is a public health challenge with a large proportion of patients suffering from&#xD;
      predominantly negative symptoms and who derive no benefit from currently available&#xD;
      treatments. Advances in neuroscience have allowed a greater understanding of negative&#xD;
      symptoms and have identified key structures and circuits believed to generate and maintain&#xD;
      them. Here, we propose the application of a targeted therapy, deep brain stimulation (DBS),&#xD;
      to alter the circuits driving negative symptoms. This is a phase I, non-blinded,&#xD;
      non-randomized, pilot trial, exploring the safety and efficacy of DBS in patients with&#xD;
      refractory negative symptoms of schizophrenia. Patients must be identified and approached by&#xD;
      their treating psychiatrist regarding this study. Patients will be given several&#xD;
      opportunities to review the study details with the investigators before the informed consent&#xD;
      is presented. All eligible patients will also be reviewed by an independent non-study&#xD;
      affiliated psychiatrist for confirmation of their diagnosis and assessment of study&#xD;
      eligibility. The total study duration will be one year for each patient, who will undergo&#xD;
      regular imaging and psychiatric analyses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No participants enrolled&#xD;
  </why_stopped>
  <start_date>September 2012</start_date>
  <completion_date type="Anticipated">December 2015</completion_date>
  <primary_completion_date type="Anticipated">September 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Schedule for the Assessment of Negative Symptoms (SANS)</measure>
    <time_frame>Change from baseline (pre-operative) SANS scores at one-year follow-up</time_frame>
    <description>Assessment of primary and enduring negative symptoms consisting of affective blunting, alogia, avolition, anhedonia/asociality and impairments in attention.&#xD;
It is numerically graded on a scale from 0 to 5; 0 being not at all present and 5 being severe.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Schizophrenia; Negative Type</condition>
  <arm_group>
    <arm_group_label>Nucleus Accumbens/Ventral Striatum (NAcc/VS) Stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The first 3 patients will have the DBS device target the NAcc/VS, which has been found to be hypoactive in patients with primarily negative symptoms.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ventral Tegmental Area (VTA) Stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>For 3 patients, the DBS device will target the VTA, which has been found to be hypoactive in patients with primarily negative symptoms.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Deep Brain Stimulation</intervention_name>
    <description>Deep Brain Stimulation (DBS) is a surgical procedure involving the implantation of a thin flexible wire called a lead. This device sends mild electric signals to an area of the brain. This study targets two different areas that we believe may be responsible for negative symptoms observed in patients with schizophrenia. There are two stages to DBS: (1) Insertion of the DBS electrodes (2) The connection of these electrodes to a battery under the collarbone.</description>
    <arm_group_label>Nucleus Accumbens/Ventral Striatum (NAcc/VS) Stimulation</arm_group_label>
    <arm_group_label>Ventral Tegmental Area (VTA) Stimulation</arm_group_label>
    <other_name>DBS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or Female patients between the age of 25-65&#xD;
&#xD;
          -  DSM IV-TR diagnosis of Schizophrenia Predominant Negative Subtype, as determined by&#xD;
             the SANS and the Schedule for the Deficit Syndrome (SDS)&#xD;
&#xD;
          -  Greater negative than positive scores on the Positive and Negative Symptoms of&#xD;
             Schizophrenia Scale (PANSS)&#xD;
&#xD;
          -  Confirmation of diagnosis by independent, non-study affiliated psychiatrist&#xD;
&#xD;
          -  Disease duration of &gt; 5 years&#xD;
&#xD;
          -  Failure of medical therapy, defined as follows:&#xD;
&#xD;
          -  Failure of a minimum of three anti-psychotic treatments for specifically negative&#xD;
             symptoms of schizophrenia (including clozapine)&#xD;
&#xD;
          -  No underlying neurological disease - No other active Axis I or Axis II co-morbidity&#xD;
             that is the focus of clinical attention&#xD;
&#xD;
          -  Able to give informed consent: i)Deemed competent by two independent psychiatrists&#xD;
             (one study psychiatrist and one non-study psychiatrist); ii) Score of &gt; 70 on&#xD;
             MacCat-CR&#xD;
&#xD;
          -  Able to comply with all testing and follow-up visit requirements defined by the Study&#xD;
             Protocol&#xD;
&#xD;
          -  Mini mental status examination (MMSE)score &gt; 25&#xD;
&#xD;
          -  Pre-menopausal women must agree to use acceptable methods of birth control (radiation&#xD;
             risk of PET)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Alcohol or substance dependence or abuse within 6 months, excluding nicotine or&#xD;
             caffeine.&#xD;
&#xD;
          -  Current suicidal ideation, plan or intent for self-harm.&#xD;
&#xD;
          -  A suicide attempt in the past 1 year&#xD;
&#xD;
          -  Diagnosis of Major Depressive Disorder or Bipolar Depression&#xD;
&#xD;
          -  Major medical illness, cardiac pacemaker/defibrillator, and other implanted stimulator&#xD;
&#xD;
          -  Likely to relocate or move to a location distant from the study site within one year&#xD;
             of enrollment&#xD;
&#xD;
          -  Any contraindication to MRI or PET scanning&#xD;
&#xD;
          -  Inability to provide consent, as well as an inability to appreciate the details and&#xD;
             risk of the trial's procedures; competence will be assessed by two independent&#xD;
             psychiatrists (one study psychiatrist, and one non-study psychiatrist)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zafiris J Daskalakis, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre for Addiction and Mental Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre for Addiction and Mental Health</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M6J 1H4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>http://www.camh.ca/en/research/Pages/research.aspx</url>
    <description>Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital, fully affiliated with the University of Toronto, and a PAHO/WHO Collaborating Centre</description>
  </link>
  <verification_date>July 2015</verification_date>
  <study_first_submitted>November 8, 2012</study_first_submitted>
  <study_first_submitted_qc>November 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 12, 2012</study_first_posted>
  <last_update_submitted>July 31, 2015</last_update_submitted>
  <last_update_submitted_qc>July 31, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 3, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centre for Addiction and Mental Health</investigator_affiliation>
    <investigator_full_name>Z. J. Daskalakis</investigator_full_name>
    <investigator_title>Chair, Temerty Centre for Therapeutic Brain Intervention</investigator_title>
  </responsible_party>
  <keyword>Schizophrenia</keyword>
  <keyword>Negative Symptoms</keyword>
  <keyword>Treatment Resistance</keyword>
  <keyword>Deep Brain Stimulation</keyword>
  <keyword>Electrical Stimulation</keyword>
  <keyword>Mental Disorders</keyword>
  <keyword>Brain Diseases</keyword>
  <keyword>Neurologic Manifestations</keyword>
  <keyword>Signs and Symptoms</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_browse>
  <!-- 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/NCT01725334
org study id: 078/2011
nct id: NCT01725334
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Schizophrenia is a complex, challenging, and heterogeneous psychiatric condition, affecting
      up to 0.5% of the population and responsible for nearly 2% of all Canadian health-care
      expenditure. Much of the morbidity of the illness is related to its negative symptoms,
      including amotivation, asociality, anhedonia and flattened emotional affect, which lead to
      functional impairment and withdrawal from social and occupational domains. In contrast to
      positive symptoms, such as hallucinations and delusions, there are currently no effective
      treatments for negative symptoms, which experts recognize are largely responsible for the
      long-term disability of a majority of patients with schizophrenia. Advances in neuroscience
      have allowed a greater understanding of negative symptoms and have identified key structures
      and circuits believed to generate and maintain them. Here, we propose the application of a
      targeted therapy, deep brain stimulation, to alter the circuits driving negative symptoms.
Schizophrenia is a public health challenge with a large proportion of patients suffering from
      predominantly negative symptoms and who derive no benefit from currently available
      treatments. Advances in neuroscience have allowed a greater understanding of negative
      symptoms and have identified key structures and circuits believed to generate and maintain
      them. Here, we propose the application of a targeted therapy, deep brain stimulation (DBS),
      to alter the circuits driving negative symptoms. This is a phase I, non-blinded,
      non-randomized, pilot trial, exploring the safety and efficacy of DBS in patients with
      refractory negative symptoms of schizophrenia. Patients must be identified and approached by
      their treating psychiatrist regarding this study. Patients will be given several
      opportunities to review the study details with the investigators before the informed consent
      is presented. All eligible patients will also be reviewed by an independent non-study
      affiliated psychiatrist for confirmation of their diagnosis and assessment of study
      eligibility. The total study duration will be one year for each patient, who will undergo
      regular imaging and psychiatric analyses.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Schedule for the Assessment of Negative Symptoms (SANS)
time frame: Change from baseline (pre-operative) SANS scores at one-year follow-up
description: Assessment of primary and enduring negative symptoms consisting of affective blunting, alogia, avolition, anhedonia/asociality and impairments in attention.
It is numerically graded on a scale from 0 to 5; 0 being not at all present and 5 being severe.
arm group label: Nucleus Accumbens/Ventral Striatum (NAcc/VS) Stimulation
arm group type: Experimental
description: The first 3 patients will have the DBS device target the NAcc/VS, which has been found to be hypoactive in patients with primarily negative symptoms.
arm group label: Ventral Tegmental Area (VTA) Stimulation
arm group type: Experimental
description: For 3 patients, the DBS device will target the VTA, which has been found to be hypoactive in patients with primarily negative symptoms.
intervention type: Procedure
intervention name: Deep Brain Stimulation
description: Deep Brain Stimulation (DBS) is a surgical procedure involving the implantation of a thin flexible wire called a lead. This device sends mild electric signals to an area of the brain. This study targets two different areas that we believe may be responsible for negative symptoms observed in patients with schizophrenia. There are two stages to DBS: (1) Insertion of the DBS electrodes (2) The connection of these electrodes to a battery under the collarbone.
arm group label: Nucleus Accumbens/Ventral Striatum (NAcc/VS) Stimulation
arm group label: Ventral Tegmental Area (VTA) Stimulation
other name: DBS
criteria: 
gender: All
minimum age: 25 Years
maximum age: 60 Years
healthy volunteers: No
last name: Zafiris J Daskalakis, MD, PhD
role: Principal Investigator
affiliation: Centre for Addiction and Mental Health
facility: 
country: Canada
url: http://www.camh.ca/en/research/Pages/research.aspx
description: Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital, fully affiliated with the University of Toronto, and a PAHO/WHO Collaborating Centre
responsible party type: Principal Investigator
investigator affiliation: Centre for Addiction and Mental Health
investigator full name: Z. J. Daskalakis
investigator title: Chair, Temerty Centre for Therapeutic Brain Intervention
mesh term: Schizophrenia