<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/NCT03034356</url>
  </required_header>
  <id_info>
    <org_study_id>MHBB-006-16S</org_study_id>
    <secondary_id>I01CX001414</secondary_id>
    <nct_id>NCT03034356</nct_id>
  </id_info>
  <brief_title>Reducing Hippocampal Hyperactivity and Improving Cognition in Schizophrenia</brief_title>
  <official_title>Reducing Hippocampal Hyperactivity and Improving Cognition in Schizophrenia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study plans to learn more about the effects of levetiracetam (LEV) on brain activity and&#xD;
      cognition in schizophrenia and schizoaffective disorder. Levetiracetam is an anti-seizure&#xD;
      drug, also called an anticonvulsant.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cognitive symptoms are not currently well-managed in Veterans with schizophrenia, leading to&#xD;
      substantially diminished quality of life. Improved treatment strategies clearly are needed.&#xD;
      Recent studies suggest taht an overactive hippocampus is associated with cognitive deficits&#xD;
      in the illness. Based on findings that the anti-epileptic drug levetiracetam (LEV) reduces&#xD;
      hippocampal activity and improves cognition in other clinical populations while being safe&#xD;
      and well-tolerated, this study will examine the effects of the drug on hippocampal activity&#xD;
      and cognition in Veterans with schizophrenia. In this crossover design, participants will&#xD;
      take LEV for 4 weeks and placebo pills for 4 weeks, but will not know the order in which they&#xD;
      are taking them.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 1, 2018</start_date>
  <completion_date type="Anticipated">September 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2023</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Neurocognitive function</measure>
    <time_frame>4 weeks</time_frame>
    <description>Cognitive function as measured by the Repeatable Battery for the Assessment of Neurological Status (RBANS)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Resting-state neuronal response</measure>
    <time_frame>4 weeks</time_frame>
    <description>Neuronal response (measured via functional magnetic resonance imaging, fMRI) in the hippocampus during rest.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>Levetiracetam, Then Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 weeks of levetiracetam administration (125 mg pill, bid), followed by a 4-week washout, then 4 weeks of placebo pill administration (bid).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo, Then Levetiracetam</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 weeks of placebo administration (bid), followed by a 4-week washout, then 4 weeks of levetiracetam administration (125 mg pill, bid).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levetiracetam</intervention_name>
    <description>Anticonvulsant drug</description>
    <arm_group_label>Levetiracetam, Then Placebo</arm_group_label>
    <arm_group_label>Placebo, Then Levetiracetam</arm_group_label>
    <other_name>Keppra</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Levetiracetam, Then Placebo</arm_group_label>
    <arm_group_label>Placebo, Then Levetiracetam</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of schizophrenia or schizoaffective disorder&#xD;
&#xD;
          -  Good general health&#xD;
&#xD;
          -  Normal vital signs (blood pressure, pulse, respiration)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Substance abuse&#xD;
&#xD;
          -  Significant neurological disorders&#xD;
&#xD;
          -  Significant head trauma/injury&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  MRI-specific exclusion criteria, e.g.,:&#xD;
&#xD;
               -  claustrophobia&#xD;
&#xD;
               -  weight&gt;400 lbs&#xD;
&#xD;
               -  metal in the body&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jason R. Tregellas, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rocky Mountain Regional VA Medical Center, Aurora, CO</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jason R Tregellas, PhD</last_name>
    <phone>(303) 315-1086</phone>
    <email>Jason.Tregellas@va.gov</email>
  </overall_contact>
  <location>
    <facility>
      <name>Rocky Mountain Regional VA Medical Center, Aurora, CO</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jason R Tregellas, PhD</last_name>
      <phone>303-315-1086</phone>
      <email>Jason.Tregellas@va.gov</email>
    </contact>
    <investigator>
      <last_name>Jason R. Tregellas, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>January 25, 2017</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 27, 2017</study_first_posted>
  <last_update_submitted>October 6, 2022</last_update_submitted>
  <last_update_submitted_qc>October 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Schizophrenia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Levetiracetam</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>A de-identified, anonymized dataset will be created and shared.</ipd_description>
  </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/NCT03034356
org study id: MHBB-006-16S
secondary id: I01CX001414
nct id: NCT03034356
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study plans to learn more about the effects of levetiracetam (LEV) on brain activity and
      cognition in schizophrenia and schizoaffective disorder. Levetiracetam is an anti-seizure
      drug, also called an anticonvulsant.
Cognitive symptoms are not currently well-managed in Veterans with schizophrenia, leading to
      substantially diminished quality of life. Improved treatment strategies clearly are needed.
      Recent studies suggest taht an overactive hippocampus is associated with cognitive deficits
      in the illness. Based on findings that the anti-epileptic drug levetiracetam (LEV) reduces
      hippocampal activity and improves cognition in other clinical populations while being safe
      and well-tolerated, this study will examine the effects of the drug on hippocampal activity
      and cognition in Veterans with schizophrenia. In this crossover design, participants will
      take LEV for 4 weeks and placebo pills for 4 weeks, but will not know the order in which they
      are taking them.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Neurocognitive function
time frame: 4 weeks
description: Cognitive function as measured by the Repeatable Battery for the Assessment of Neurological Status (RBANS)
measure: Resting-state neuronal response
time frame: 4 weeks
description: Neuronal response (measured via functional magnetic resonance imaging, fMRI) in the hippocampus during rest.
arm group label: Levetiracetam, Then Placebo
arm group type: Experimental
description: 4 weeks of levetiracetam administration (125 mg pill, bid), followed by a 4-week washout, then 4 weeks of placebo pill administration (bid).
arm group label: Placebo, Then Levetiracetam
arm group type: Experimental
description: 4 weeks of placebo administration (bid), followed by a 4-week washout, then 4 weeks of levetiracetam administration (125 mg pill, bid).
intervention type: Drug
intervention name: Levetiracetam
description: Anticonvulsant drug
arm group label: Levetiracetam, Then Placebo
arm group label: Placebo, Then Levetiracetam
other name: Keppra
intervention type: Drug
intervention name: Placebo
description: Placebo
arm group label: Levetiracetam, Then Placebo
arm group label: Placebo, Then Levetiracetam
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jason R. Tregellas, PhD
role: Principal Investigator
affiliation: Rocky Mountain Regional VA Medical Center, Aurora, CO
last name: Jason R Tregellas, PhD
phone: (303) 315-1086
email: Jason.Tregellas@va.gov
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Levetiracetam
sharing ipd: Yes
ipd description: A de-identified, anonymized dataset will be created and shared.