<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/NCT03781115</url>
  </required_header>
  <id_info>
    <org_study_id>1612051594</org_study_id>
    <nct_id>NCT03781115</nct_id>
  </id_info>
  <brief_title>Proposal To Develop A Rapid And Cost-Effective Diagnostic Test For Schizophrenia</brief_title>
  <official_title>Proposal To Develop A Rapid And Cost-Effective Diagnostic Test For Schizophrenia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Arizona</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sidney R. Baer, Jr. Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Arizona</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Schizophrenia is a severe psychotic illness of unknown cause that affects 1% of the&#xD;
      population worldwide. Currently, there is no diagnostic test for schizophrenia. Instead, the&#xD;
      diagnosis is typically established through a psychiatric interview of the patient, who is&#xD;
      evaluated against a set of established criteria of signs and symptoms. It can take many&#xD;
      months to years to establish a diagnosis of schizophrenia and achieve an appropriate&#xD;
      treatment regimen to attain resolution of the patient's symptoms. This process is&#xD;
      particularly challenging in areas of limited access to specialists a problem not only in&#xD;
      third world countries and rural regions, but throughout the United States where there can be&#xD;
      long waits to obtain an appointment with a psychiatrist. The present research experiment&#xD;
      investigates a potential novel method for diagnosing schizophrenia.&#xD;
&#xD;
      The overall objective of the study is to test the hypothesis that patients with schizophrenia&#xD;
      will have a heightened tolerance to the sedating effects of anti-psychotic medications, which&#xD;
      will be reflected in differences in their electroencephalogram (EEG) when compared to healthy&#xD;
      normal controls. The investigators expect that the schizophrenia patients will score on the&#xD;
      &quot;more alert&quot; and &quot;less sleepy&quot; ends of these scales, and that the normal control subjects&#xD;
      will show the opposite response. A patient that fails to become sedated or experience the&#xD;
      sleepiness side effects, typically caused by the anti-psychotic medication, may support the&#xD;
      existing diagnosis of schizophrenia. Measures of the subjects' level of sedation that are&#xD;
      found to correlate significantly with EEG response and diagnosis will be used to create a&#xD;
      diagnostic test. This simple and inexpensive test will consist of a single dosage of&#xD;
      anti-psychotic medication, and a rapid assessment tool with scores that have a high degree of&#xD;
      predictive validity for the diagnosis of schizophrenia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The overall objective of the study is to test the hypothesis that patients with schizophrenia&#xD;
      will have a heightened tolerance to the sedating effects of antipsychotic medications, which&#xD;
      will be reflected in differences in the participants' electroencephalogram response (EEG),&#xD;
      when compared to healthy control participants.The following Specific Aims are designed to&#xD;
      test this hypothesis and create the diagnostic tool.&#xD;
&#xD;
      Specific Aim 1: The investigators will first conduct a pilot dose-response evaluation of the&#xD;
      anti-psychotic drugs ziprasidone (Geodon) (20, 40, or 60 mg tablet) and olanzapine (Zyprexa®)&#xD;
      (2.5, 5, 7.5, or 10 mg tablet) in non-psychiatric ill control participants to determine the&#xD;
      optimal dosage that promotes sedation in healthy participants versus a placebo. The&#xD;
      evaluation will comprise of a physical examination and questionnaires. The investigators will&#xD;
      start with the lowest dose of each drug and if the dosage fails to induce sedation in healthy&#xD;
      participants, the investigators will repeat the pilot dose-response evaluation with the next&#xD;
      higher dose until the maximum dose is reached for both drugs. Specific Aim 2. To determine&#xD;
      whether the pattern of EEG activity in response to a single dose of the anti-psychotic&#xD;
      medication determined from the dose-response study from Aim 1 distinguishes schizophrenia&#xD;
      participants from normal controls. The investigators will start with 2-4 healthy control&#xD;
      participants to determine that the results show a discernible effect on the EEG using the&#xD;
      dosage from Aim 1. If the dose of anti-psychotic medication fails to show an effect on the&#xD;
      EEG the investigators will increase the dosage until the maximum dosage of the chosen&#xD;
      medication is used. Once the dosage is identified the investigators will move onto getting&#xD;
      IRB approval to evaluate participants diagnosed with schizophrenia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 20, 2017</start_date>
  <completion_date type="Anticipated">January 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>The investigators will first conduct a dose-response evaluation of the anti-psychotic drug ziprasidone (Geodon) (20, 40, or 60 mg tablet) or olanzapine (Zyprexa®) (2.5, 5, 7.5, or 10 mg tablet) in non-psychiatric ill control individuals to determine the dosage that promotes sedation in individuals versus a placebo. The evaluation will comprise of a physical examination, drug/pregnancy screenings and sleepiness questionnaires. Once the dosage of the anti-psychotic medication is determined new healthy subjects will be recruited to ingest the medication and have an electroencephalogram (EEG) recording taken. If the dosage of medication does not show an effect on the EEG the investigators will ask the individual to come back on a different day so the next higher dose of medication can be given. Once a the healthy subject's EEG shows an effect new control subjects and individuals with a diagnosis of schizophrenia will be recruited.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double Blind Masking: The participant and the investigator are both blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Heart Rate</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Evaluating the heart rate of the subject every hour during all the test procedures</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pulse Rate</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Evaluating the pulse rate of the subject every hour during all the test procedures</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Stanford Sleepiness Scale</measure>
    <time_frame>up to 2 years</time_frame>
    <description>The subject will rate how sleepy they are feeling at baseline and every hour during the test using an (8) point scale (i.e. 1= feeling active, vital alert, or wide awake; 2= functioning at high levels, but not fully alert; 3= awake, but relaxed, responsive but not fully alert; 4= somewhat foggy, let down; 5= foggy, losing interest in remaining awake, slowed down; 6= sleepy, woozy, fighting sleep, prefer to lay down; 7= no longer fighting sleep, sleep onset soon, having dream-like thoughts; 8= asleep</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Epworth Sleepiness Scale</measure>
    <time_frame>up to 2 years</time_frame>
    <description>The subject will rate their pre-test sleepiness only once during the test using a (4) point scale (0= no chance of dosing, 1= slight chance of dosing, 2= moderate chance of dozing and 3= high chance of dozing</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fatigue Severity Scale</measure>
    <time_frame>up to 2 years</time_frame>
    <description>The subject will rate their pre-test fatigue only once during the test by rating 10 questions using a slide scale between 1 and 7. A rating of 1 means the subject strongly disagrees with the statement. A rating of 7 means the subject strongly agrees with the statement.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Chalder Fatigue Scale</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Subjects will rate their fatigue every hour and at baseline by answering 11 questions and rating their fatigue using a 4 point scale (i.e. less than usual, no more than usual, more than usual and much more than usual)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Psychomotor physical computerized test</measure>
    <time_frame>up to 2 years</time_frame>
    <description>The participants uses a computerized test to test their reflexes every hour and at baseline during the trial period. Every time a red dot appears in the middle of the screen the participant must touch the computer screen as fast as they can. This test was measured in how fast they responded (ms) and by how many attempts to touch the screen were recorded in 2 minutes</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hand Fatigue Scale</measure>
    <time_frame>up to 2 years</time_frame>
    <description>A hand grip measuring device will be used to test for fatigue. A small hand held device will measure the participants hand grip strength every hour during the test and at baseline.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Electroencephalogram</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Electroencephalogram will be taken at baseline and after subjects have taken the anti-psychotic medication. There will be no placebo taken for this test.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>Ziprasidone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The investigators will conduct a pilot dose-response evaluation of a single dose of the anti-psychotic drug ziprasidone (Geodon). The investigators will start with a single 20mg pill given to (3) subjects and will increase the dosage in sequential subjects until the desired sedation effect is achieved (i.e. 40 and 60mg tablets). If Ziprasidone causes the desired sedation effect additional healthy subjects will be recruited to take the medication and have an electroencephalogram (EEG) taken.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Olanzapine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The investigators will conduct a pilot dose-response evaluation of a single dose of the anti-psychotic drug olanzapine (Zyprexa). The investigators will start with a single 2.5 mg pill given to (3) subjects and will increase the dosage in sequential subjects until the desired sedation effect is achieved (i.e. 5, 7.5, and 10 mg tablets).If olanzapine causes the desired sedation effect additional healthy subjects will be recruited to take the medication and have an electroencephalogram (EEG).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Comparator</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The investigators have prepared a placebo which duplicates the exact color and size of the study drug capsule to use as a non-drug control.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ziprasidone</intervention_name>
    <description>anti-psychotic drug proposed for use as rapid diagnostic tool</description>
    <arm_group_label>Placebo Comparator</arm_group_label>
    <arm_group_label>Ziprasidone</arm_group_label>
    <other_name>Geodon</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olanzapine</intervention_name>
    <description>anti-psychotic drug proposed for use as rapid diagnostic tool</description>
    <arm_group_label>Olanzapine</arm_group_label>
    <arm_group_label>Ziprasidone</arm_group_label>
    <other_name>Zyprexa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Comparator</intervention_name>
    <description>A non drug oral placebo capsule will be given as a control</description>
    <arm_group_label>Olanzapine</arm_group_label>
    <arm_group_label>Placebo Comparator</arm_group_label>
    <arm_group_label>Ziprasidone</arm_group_label>
    <other_name>Placebo Oral Capsule</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria Healthy Control&#xD;
&#xD;
          1. Be between 18 and 40 years of age&#xD;
&#xD;
          2. Be able to understand English&#xD;
&#xD;
          3. Have no history of psychosis&#xD;
&#xD;
          4. Have no history of sleep apnea, heart condition or seizure&#xD;
&#xD;
          5. Have no known drug allergies&#xD;
&#xD;
          6. The ability to swallow a pill&#xD;
&#xD;
        Exclusion Criteria Healthy control&#xD;
&#xD;
          1. Refuse to sign the consent form&#xD;
&#xD;
          2. Drink caffeine or alcohol within 24 hours of the study&#xD;
&#xD;
          3. Have the EKG readout report borderline or abnormal ECG&#xD;
&#xD;
          4. Have the 12 panel urine drug screen show a positive result&#xD;
&#xD;
          5. Be pregnant&#xD;
&#xD;
        Inclusion Criteria Schizophrenic subject&#xD;
&#xD;
          1. Be between 18 and 40 years of age&#xD;
&#xD;
          2. Be able to understand English&#xD;
&#xD;
          3. Have been diagnosed with a Schizophrenia Spectrum or other psychotic disorder&#xD;
&#xD;
          4. Belong to one of three groups:&#xD;
&#xD;
               1. Never medicated patients with a first episode of psychosis&#xD;
&#xD;
               2. Have not received long acting injectable (depot) antipsychotic in previous 6&#xD;
                  months&#xD;
&#xD;
               3. Have not received oral antipsychotic (or antidepressant that has serotonergic&#xD;
                  action) in previous 2 weeks&#xD;
&#xD;
          5. Have no history of sleep apnea, heart condition or seizure&#xD;
&#xD;
          6. Have no known drug allergies&#xD;
&#xD;
          7. Be able to swallow a pill&#xD;
&#xD;
          8. Healthy as determined by teh enrolling physician(s)&#xD;
&#xD;
        Exclusion Criteria Schizophrenic subject&#xD;
&#xD;
          1. Refuse to sign the consent form&#xD;
&#xD;
          2. Drink caffeine or alcohol within 24 hours of the study&#xD;
&#xD;
          3. Have the EKG readout report borderline or abnormal ECG&#xD;
&#xD;
          4. Have the 12 panel urine drug screen show a positive result&#xD;
&#xD;
          5. Be pregnant&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Amelia Gallitano, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Arizona College of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Janet Campbell, MS</last_name>
    <phone>602-827-2875</phone>
    <email>janetcampbell@email.arizona.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Amelia Gallitano, MD/PhD</last_name>
    <phone>6028272131</phone>
    <email>amelia@email.arizona.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Banner Alzheimer's Institute</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85006</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Banner University Medical Center</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85006</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Steve Chung, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Cutler NR. Pharmacokinetic studies of antipsychotics in healthy volunteers versus patients. J Clin Psychiatry. 2001;62 Suppl 5:10-3; discussion 23-4.</citation>
    <PMID>11305842</PMID>
  </reference>
  <reference>
    <citation>Gallitano-Mendel A, Izumi Y, Tokuda K, Zorumski CF, Howell MP, Muglia LJ, Wozniak DF, Milbrandt J. The immediate early gene early growth response gene 3 mediates adaptation to stress and novelty. Neuroscience. 2007 Sep 7;148(3):633-43. doi: 10.1016/j.neuroscience.2007.05.050. Epub 2007 Aug 9.</citation>
    <PMID>17692471</PMID>
  </reference>
  <reference>
    <citation>Gallitano-Mendel A, Wozniak DF, Pehek EA, Milbrandt J. Mice lacking the immediate early gene Egr3 respond to the anti-aggressive effects of clozapine yet are relatively resistant to its sedating effects. Neuropsychopharmacology. 2008 May;33(6):1266-75. doi: 10.1038/sj.npp.1301505. Epub 2007 Jul 18.</citation>
    <PMID>17637609</PMID>
  </reference>
  <reference>
    <citation>Williams AA, Ingram WM, Levine S, Resnik J, Kamel CM, Lish JR, Elizalde DI, Janowski SA, Shoker J, Kozlenkov A, Gonzalez-Maeso J, Gallitano AL. Reduced levels of serotonin 2A receptors underlie resistance of Egr3-deficient mice to locomotor suppression by clozapine. Neuropsychopharmacology. 2012 Sep;37(10):2285-98. doi: 10.1038/npp.2012.81. Epub 2012 Jun 13.</citation>
    <PMID>22692564</PMID>
  </reference>
  <reference>
    <citation>Selvaraj S, Arnone D, Cappai A, Howes O. Alterations in the serotonin system in schizophrenia: a systematic review and meta-analysis of postmortem and molecular imaging studies. Neurosci Biobehav Rev. 2014 Sep;45:233-45. doi: 10.1016/j.neubiorev.2014.06.005. Epub 2014 Jun 24.</citation>
    <PMID>24971825</PMID>
  </reference>
  <reference>
    <citation>Everson G, Lasseter KC, Anderson KE, Bauer LA, Carithens RL Jr, Wilner KD, Johnson A, Anziano RJ, Smolarek TA, Turncliff RZ. The pharmacokinetics of ziprasidone in subjects with normal and impaired hepatic function. Br J Clin Pharmacol. 2000;49 Suppl 1(Suppl 1):21S-26S. doi: 10.1046/j.1365-2125.2000.00149.x.</citation>
    <PMID>10771450</PMID>
  </reference>
  <reference>
    <citation>Albaugh VL, Singareddy R, Mauger D, Lynch CJ. A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers. PLoS One. 2011;6(8):e22662. doi: 10.1371/journal.pone.0022662. Epub 2011 Aug 9.</citation>
    <PMID>21857944</PMID>
  </reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>October 13, 2017</study_first_submitted>
  <study_first_submitted_qc>December 17, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>February 23, 2022</last_update_submitted>
  <last_update_submitted_qc>February 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>schizophrenia, psychosis, ziprasidone, olanzapine</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>Olanzapine</mesh_term>
    <mesh_term>Ziprasidone</mesh_term>
  </intervention_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/NCT03781115
org study id: 1612051594
nct id: NCT03781115
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Schizophrenia is a severe psychotic illness of unknown cause that affects 1% of the
      population worldwide. Currently, there is no diagnostic test for schizophrenia. Instead, the
      diagnosis is typically established through a psychiatric interview of the patient, who is
      evaluated against a set of established criteria of signs and symptoms. It can take many
      months to years to establish a diagnosis of schizophrenia and achieve an appropriate
      treatment regimen to attain resolution of the patient's symptoms. This process is
      particularly challenging in areas of limited access to specialists a problem not only in
      third world countries and rural regions, but throughout the United States where there can be
      long waits to obtain an appointment with a psychiatrist. The present research experiment
      investigates a potential novel method for diagnosing schizophrenia.

      The overall objective of the study is to test the hypothesis that patients with schizophrenia
      will have a heightened tolerance to the sedating effects of anti-psychotic medications, which
      will be reflected in differences in their electroencephalogram (EEG) when compared to healthy
      normal controls. The investigators expect that the schizophrenia patients will score on the
      "more alert" and "less sleepy" ends of these scales, and that the normal control subjects
      will show the opposite response. A patient that fails to become sedated or experience the
      sleepiness side effects, typically caused by the anti-psychotic medication, may support the
      existing diagnosis of schizophrenia. Measures of the subjects' level of sedation that are
      found to correlate significantly with EEG response and diagnosis will be used to create a
      diagnostic test. This simple and inexpensive test will consist of a single dosage of
      anti-psychotic medication, and a rapid assessment tool with scores that have a high degree of
      predictive validity for the diagnosis of schizophrenia.
The overall objective of the study is to test the hypothesis that patients with schizophrenia
      will have a heightened tolerance to the sedating effects of antipsychotic medications, which
      will be reflected in differences in the participants' electroencephalogram response (EEG),
      when compared to healthy control participants.The following Specific Aims are designed to
      test this hypothesis and create the diagnostic tool.

      Specific Aim 1: The investigators will first conduct a pilot dose-response evaluation of the
      anti-psychotic drugs ziprasidone (Geodon) (20, 40, or 60 mg tablet) and olanzapine (Zyprexa®)
      (2.5, 5, 7.5, or 10 mg tablet) in non-psychiatric ill control participants to determine the
      optimal dosage that promotes sedation in healthy participants versus a placebo. The
      evaluation will comprise of a physical examination and questionnaires. The investigators will
      start with the lowest dose of each drug and if the dosage fails to induce sedation in healthy
      participants, the investigators will repeat the pilot dose-response evaluation with the next
      higher dose until the maximum dose is reached for both drugs. Specific Aim 2. To determine
      whether the pattern of EEG activity in response to a single dose of the anti-psychotic
      medication determined from the dose-response study from Aim 1 distinguishes schizophrenia
      participants from normal controls. The investigators will start with 2-4 healthy control
      participants to determine that the results show a discernible effect on the EEG using the
      dosage from Aim 1. If the dose of anti-psychotic medication fails to show an effect on the
      EEG the investigators will increase the dosage until the maximum dosage of the chosen
      medication is used. Once the dosage is identified the investigators will move onto getting
      IRB approval to evaluate participants diagnosed with schizophrenia.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The investigators will first conduct a dose-response evaluation of the anti-psychotic drug ziprasidone (Geodon) (20, 40, or 60 mg tablet) or olanzapine (Zyprexa®) (2.5, 5, 7.5, or 10 mg tablet) in non-psychiatric ill control individuals to determine the dosage that promotes sedation in individuals versus a placebo. The evaluation will comprise of a physical examination, drug/pregnancy screenings and sleepiness questionnaires. Once the dosage of the anti-psychotic medication is determined new healthy subjects will be recruited to ingest the medication and have an electroencephalogram (EEG) recording taken. If the dosage of medication does not show an effect on the EEG the investigators will ask the individual to come back on a different day so the next higher dose of medication can be given. Once a the healthy subject's EEG shows an effect new control subjects and individuals with a diagnosis of schizophrenia will be recruited.
primary purpose: Diagnostic
masking: Double (Participant, Investigator)
masking description: Double Blind Masking: The participant and the investigator are both blinded.
measure: Heart Rate
time frame: up to 2 years
description: Evaluating the heart rate of the subject every hour during all the test procedures
measure: Pulse Rate
time frame: up to 2 years
description: Evaluating the pulse rate of the subject every hour during all the test procedures
measure: Stanford Sleepiness Scale
time frame: up to 2 years
description: The subject will rate how sleepy they are feeling at baseline and every hour during the test using an (8) point scale (i.e. 1= feeling active, vital alert, or wide awake; 2= functioning at high levels, but not fully alert; 3= awake, but relaxed, responsive but not fully alert; 4= somewhat foggy, let down; 5= foggy, losing interest in remaining awake, slowed down; 6= sleepy, woozy, fighting sleep, prefer to lay down; 7= no longer fighting sleep, sleep onset soon, having dream-like thoughts; 8= asleep
measure: Epworth Sleepiness Scale
time frame: up to 2 years
description: The subject will rate their pre-test sleepiness only once during the test using a (4) point scale (0= no chance of dosing, 1= slight chance of dosing, 2= moderate chance of dozing and 3= high chance of dozing
measure: Fatigue Severity Scale
time frame: up to 2 years
description: The subject will rate their pre-test fatigue only once during the test by rating 10 questions using a slide scale between 1 and 7. A rating of 1 means the subject strongly disagrees with the statement. A rating of 7 means the subject strongly agrees with the statement.
measure: Chalder Fatigue Scale
time frame: up to 2 years
description: Subjects will rate their fatigue every hour and at baseline by answering 11 questions and rating their fatigue using a 4 point scale (i.e. less than usual, no more than usual, more than usual and much more than usual)
measure: Psychomotor physical computerized test
time frame: up to 2 years
description: The participants uses a computerized test to test their reflexes every hour and at baseline during the trial period. Every time a red dot appears in the middle of the screen the participant must touch the computer screen as fast as they can. This test was measured in how fast they responded (ms) and by how many attempts to touch the screen were recorded in 2 minutes
measure: Hand Fatigue Scale
time frame: up to 2 years
description: A hand grip measuring device will be used to test for fatigue. A small hand held device will measure the participants hand grip strength every hour during the test and at baseline.
measure: Electroencephalogram
time frame: up to 2 years
description: Electroencephalogram will be taken at baseline and after subjects have taken the anti-psychotic medication. There will be no placebo taken for this test.
arm group label: Ziprasidone
arm group type: Experimental
description: The investigators will conduct a pilot dose-response evaluation of a single dose of the anti-psychotic drug ziprasidone (Geodon). The investigators will start with a single 20mg pill given to (3) subjects and will increase the dosage in sequential subjects until the desired sedation effect is achieved (i.e. 40 and 60mg tablets). If Ziprasidone causes the desired sedation effect additional healthy subjects will be recruited to take the medication and have an electroencephalogram (EEG) taken.
arm group label: Olanzapine
arm group type: Experimental
description: The investigators will conduct a pilot dose-response evaluation of a single dose of the anti-psychotic drug olanzapine (Zyprexa). The investigators will start with a single 2.5 mg pill given to (3) subjects and will increase the dosage in sequential subjects until the desired sedation effect is achieved (i.e. 5, 7.5, and 10 mg tablets).If olanzapine causes the desired sedation effect additional healthy subjects will be recruited to take the medication and have an electroencephalogram (EEG).
arm group label: Placebo Comparator
arm group type: Placebo Comparator
description: The investigators have prepared a placebo which duplicates the exact color and size of the study drug capsule to use as a non-drug control.
intervention type: Drug
intervention name: Ziprasidone
description: anti-psychotic drug proposed for use as rapid diagnostic tool
arm group label: Placebo Comparator
arm group label: Ziprasidone
other name: Geodon
intervention type: Drug
intervention name: Olanzapine
description: anti-psychotic drug proposed for use as rapid diagnostic tool
arm group label: Olanzapine
arm group label: Ziprasidone
other name: Zyprexa
intervention type: Drug
intervention name: Placebo Comparator
description: A non drug oral placebo capsule will be given as a control
arm group label: Olanzapine
arm group label: Placebo Comparator
arm group label: Ziprasidone
other name: Placebo Oral Capsule
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Amelia Gallitano, MD,PhD
role: Principal Investigator
affiliation: University of Arizona College of Medicine
last name: Janet Campbell, MS
phone: 602-827-2875
email: janetcampbell@email.arizona.edu
last name: Amelia Gallitano, MD/PhD
phone: 6028272131
email: amelia@email.arizona.edu
facility: 
status: Recruiting
facility: 
status: Recruiting
investigator: 
country: United States
citation: Cutler NR. Pharmacokinetic studies of antipsychotics in healthy volunteers versus patients. J Clin Psychiatry. 2001;62 Suppl 5:10-3; discussion 23-4.
PMID: 11305842
citation: Gallitano-Mendel A, Izumi Y, Tokuda K, Zorumski CF, Howell MP, Muglia LJ, Wozniak DF, Milbrandt J. The immediate early gene early growth response gene 3 mediates adaptation to stress and novelty. Neuroscience. 2007 Sep 7;148(3):633-43. doi: 10.1016/j.neuroscience.2007.05.050. Epub 2007 Aug 9.
PMID: 17692471
citation: Gallitano-Mendel A, Wozniak DF, Pehek EA, Milbrandt J. Mice lacking the immediate early gene Egr3 respond to the anti-aggressive effects of clozapine yet are relatively resistant to its sedating effects. Neuropsychopharmacology. 2008 May;33(6):1266-75. doi: 10.1038/sj.npp.1301505. Epub 2007 Jul 18.
PMID: 17637609
citation: Williams AA, Ingram WM, Levine S, Resnik J, Kamel CM, Lish JR, Elizalde DI, Janowski SA, Shoker J, Kozlenkov A, Gonzalez-Maeso J, Gallitano AL. Reduced levels of serotonin 2A receptors underlie resistance of Egr3-deficient mice to locomotor suppression by clozapine. Neuropsychopharmacology. 2012 Sep;37(10):2285-98. doi: 10.1038/npp.2012.81. Epub 2012 Jun 13.
PMID: 22692564
citation: Selvaraj S, Arnone D, Cappai A, Howes O. Alterations in the serotonin system in schizophrenia: a systematic review and meta-analysis of postmortem and molecular imaging studies. Neurosci Biobehav Rev. 2014 Sep;45:233-45. doi: 10.1016/j.neubiorev.2014.06.005. Epub 2014 Jun 24.
PMID: 24971825
citation: Everson G, Lasseter KC, Anderson KE, Bauer LA, Carithens RL Jr, Wilner KD, Johnson A, Anziano RJ, Smolarek TA, Turncliff RZ. The pharmacokinetics of ziprasidone in subjects with normal and impaired hepatic function. Br J Clin Pharmacol. 2000;49 Suppl 1(Suppl 1):21S-26S. doi: 10.1046/j.1365-2125.2000.00149.x.
PMID: 10771450
citation: Albaugh VL, Singareddy R, Mauger D, Lynch CJ. A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers. PLoS One. 2011;6(8):e22662. doi: 10.1371/journal.pone.0022662. Epub 2011 Aug 9.
PMID: 21857944
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Olanzapine
mesh term: Ziprasidone
sharing ipd: No