<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/NCT03838484</url>
  </required_header>
  <id_info>
    <org_study_id>190021</org_study_id>
    <secondary_id>7K23MH116339</secondary_id>
    <nct_id>NCT03838484</nct_id>
  </id_info>
  <brief_title>Effects of Transdermal Nicotine on Response Inhibition to Emotional Cues in Schizophrenia</brief_title>
  <official_title>Effects of Transdermal Nicotine on Response Inhibition to Emotional Cues in Schizophrenia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</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>
      The purpose of this study is to test whether nicotine, a drug that activates receptors called&#xD;
      nicotinic acetylcholine receptors in the brain, improves the ability to make or withhold&#xD;
      responses to faces that are either emotionally neutral or emotionally negative. This study&#xD;
      will also test whether the drug affects brain activity while making or withholding responses&#xD;
      using electroencephalography. Previous studies in people with schizophrenia have shown that&#xD;
      more errors in response to negative emotional cues are related to greater likelihood of&#xD;
      impulsive aggressive behavior. Therefore, the aim of this study is to determine whether&#xD;
      nicotine might be a new strategy to reduce aggressive behavior. The investigators' goal is 25&#xD;
      individuals with schizophrenia and 25 healthy controls to complete the study at Vanderbilt.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This human laboratory study seeks to test the hypothesis that activation of nicotinic&#xD;
      acetylcholine receptors (nAChRs) in the brain will reduce impulsive behavior in response to&#xD;
      negative emotional cues as compared to neutral emotional cues. Because impulsive action&#xD;
      during negative mood states is strongly correlated with impulsive aggression in both healthy&#xD;
      individuals and individuals with schizophrenia (discussed below), the investigators'&#xD;
      overarching, long-term goal is to determine whether nAChRs in general as well as specific&#xD;
      nAChR subclasses might represent novel treatment targets to reduce impulsive aggressive&#xD;
      behavior, a significant public health problem.&#xD;
&#xD;
      Nicotinic acetylcholine receptors are a large family of excitatory, pentameric, ionotropic,&#xD;
      ligand-gated ion channels located throughout the brain and the remainder of the body. Their&#xD;
      endogenous ligand is acetylcholine, yet this family is defined by their common activation by&#xD;
      nicotine. Interestingly, anti-aggressive, or &quot;serenic&quot; effects of nicotine have been&#xD;
      demonstrated across a number of animal models, including mice, rats, and non-human primates,&#xD;
      and multiple human laboratory studies demonstrate an anti-aggressive effect of nicotine in&#xD;
      humans. The investigators' laboratory has also demonstrated that acute administration of&#xD;
      nicotine at relatively low doses results in reduction of aggressive behaviors in mouse&#xD;
      models. Because nicotine is active at all nAChRs, the investigators explored this mechanism&#xD;
      further and found that hippocampal alpha-7 nAChRs were both necessary and sufficient for&#xD;
      nicotine's serenic effect. Consistent with these findings, there is substantial evidence in&#xD;
      humans that reduction of alpha-7 nAChR signaling enhances aggressive behavior, including in&#xD;
      individuals with 15q13.3 microdeletion syndrome, a genetic disorder resulting from the&#xD;
      deletion of the region of chromosome 15 containing the gene coding for alpha-7 nAChRs. The&#xD;
      investigators have also translated these findings into human clinical populations, finding&#xD;
      recently the safety and efficacy of transdermal nicotine to reduce aggression and&#xD;
      irritability in young adults with autism spectrum disorder. This work, along with other&#xD;
      previous case studies in humans, supports targeting nAChRs using transdermal nicotine to&#xD;
      reduce aggressive behaviors.&#xD;
&#xD;
      Urgency is a behavioral construct defined as the tendency to act rashly in the context of&#xD;
      strong positive or negative emotion, and explains a large degree of variance in the&#xD;
      development of impulsive aggression in subjects with schizophrenia and other populations&#xD;
      without psychiatric disorders. In patients with schizophrenia, degree of urgency correlates&#xD;
      with structural and functional changes in a neuronal network involving prefrontal cortical&#xD;
      and limbic/cognitive control brain regions. A number of previous studies have similarly&#xD;
      demonstrated impulsivity in the context of negative emotion, called &quot;negative urgency&quot;,&#xD;
      correlates with history of aggression, as well as substance use and other risky behaviors.&#xD;
      Urgency is a hereditable trait that may be considered an endophenotype of impulsive&#xD;
      aggression.&#xD;
&#xD;
      Recent studies in humans have explored the relationship between mood-related impulsivity&#xD;
      (i.e. urgency) and aggressive behavior using an Emotional Go/NoGo task. This task measures&#xD;
      responding or response withholding to visual stimuli of neutral or emotional (typically&#xD;
      negative) valence, and quantifies reaction time and commission/omission errors as a function&#xD;
      of stimulus valence. Using an Emotional Go/NoGo task, Krakowski et al. studied healthy&#xD;
      controls, patients with schizophrenia with or without a history of violence, and&#xD;
      non-psychotic individuals with history of violence. In all groups, emotional valence had a&#xD;
      significant effect on error commission. In schizophrenia patients, individuals with history&#xD;
      of violence were significantly faster to make an incorrect response to negative stimuli (i.e.&#xD;
      not withhold a response) than patients without history of violence, whereas the two groups&#xD;
      did not differ in response times to neutral valence stimuli. Other studies have also&#xD;
      demonstrated an interaction between emotional valence and impulsive errors in schizophrenia,&#xD;
      as well as a relationship between emotional valence, impulsive errors, history of violence,&#xD;
      and frontal cortex 5-HT1B receptor binding.&#xD;
&#xD;
      While the investigators' studies in mice suggest a direct effect of nAChR stimulation on&#xD;
      aggression through activation of the alpha-7 nAChR and are supported by the results using&#xD;
      transdermal nicotine in humans, to the investigators' knowledge no previous studies have&#xD;
      directly examined the relationship between pharmacological targeting of nAChRs using&#xD;
      transdermal nicotine and effects on impulsivity in the context of emotional cues in humans.&#xD;
      The investigators now aim to directly test this hypothesis using an Emotional Go/NoGo task in&#xD;
      subjects with schizophrenia and healthy controls to determine whether transdermal nicotine&#xD;
      improves impulsive behavior and neural correlates in the context of negative and neutral&#xD;
      valence cues. Given the relationship between impulsivity and aggressive behavior, the&#xD;
      findings of this proposed study will strongly inform future studies of targeting nAChRs&#xD;
      broadly and alpha-7 nAChRs more specifically to identify novel treatments for individuals&#xD;
      with severe neuropsychiatric disorders struggling with persistent pathological impulsive&#xD;
      aggression.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Recruitment challenges due to Covid19.&#xD;
  </why_stopped>
  <start_date type="Actual">May 10, 2019</start_date>
  <completion_date type="Actual">February 24, 2020</completion_date>
  <primary_completion_date type="Actual">February 24, 2020</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>False Alarm Error Rate</measure>
    <time_frame>Week 1</time_frame>
    <description>Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key (&quot;Go&quot;) or withhold pressing a key (&quot;NoGo&quot;). The False Alarm Error Rate will be measured by the proportion of incorrect responses.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>False Alarm Error Rate</measure>
    <time_frame>Week 2</time_frame>
    <description>Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key (&quot;Go&quot;) or withhold pressing a key (&quot;NoGo&quot;). The False Alarm Error Rate will be measured by the proportion of incorrect responses.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Omission Error Rate</measure>
    <time_frame>Week 1</time_frame>
    <description>Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key (&quot;Go&quot;) or withhold pressing a key (&quot;NoGo&quot;). The Omission Error Rate will be measured by the proportion of questions asked with a failure to respond.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Omission Error Rate</measure>
    <time_frame>Week 2</time_frame>
    <description>Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key (&quot;Go&quot;) or withhold pressing a key (&quot;NoGo&quot;). The Omission Error Rate will be measured by the proportion of questions asked with a failure to respond.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Reaction Time for Correct Hits</measure>
    <time_frame>Week 1</time_frame>
    <description>Time taken from stimulus presentation to button push during Go trials</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Reaction Time for Correct Hits</measure>
    <time_frame>Week 2</time_frame>
    <description>Time taken from stimulus presentation to button push during Go trials</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Reaction Time for False Alarms</measure>
    <time_frame>Week 1</time_frame>
    <description>Time taken from stimulus presentation to button push during NoGo trials</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Reaction Time for False Alarms</measure>
    <time_frame>Week 2</time_frame>
    <description>Time taken from stimulus presentation to button push during NoGo trials</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Schizophrenia</condition>
  <condition>Impulsive Behavior</condition>
  <arm_group>
    <arm_group_label>Healthy: placebo first, nicotine last</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy controls will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy: nicotine first, placebo last</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy controls will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SCZ: placebo first, nicotine last</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with schizophrenia (SCZ) will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SCZ: nicotine first, placebo last</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects with schizophrenia (SCZ) will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nicotine Patch, 7 Mg/24 Hr</intervention_name>
    <description>Nicotine patch, 7 mg/24 hour will be applied to the skin.</description>
    <arm_group_label>Healthy: nicotine first, placebo last</arm_group_label>
    <arm_group_label>Healthy: placebo first, nicotine last</arm_group_label>
    <arm_group_label>SCZ: nicotine first, placebo last</arm_group_label>
    <arm_group_label>SCZ: placebo first, nicotine last</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo patch</intervention_name>
    <description>Placebo skin patch will be applied to the skin.</description>
    <arm_group_label>Healthy: nicotine first, placebo last</arm_group_label>
    <arm_group_label>Healthy: placebo first, nicotine last</arm_group_label>
    <arm_group_label>SCZ: nicotine first, placebo last</arm_group_label>
    <arm_group_label>SCZ: placebo first, nicotine last</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria for schizophrenia subjects:&#xD;
&#xD;
          1. Men and women age 18 - 65.&#xD;
&#xD;
          2. Communicative in English.&#xD;
&#xD;
          3. Provide voluntary, written informed consent.&#xD;
&#xD;
          4. Physically healthy by medical history,and ECG examination.&#xD;
&#xD;
          5. BMI &gt; 17.5 and &lt; 45.&#xD;
&#xD;
          6. Diagnosis of schizophrenia (ICD-10 F20) or schizoaffective disorder (ICD-10 F25)&#xD;
             confirmed by Structured Clinical Interview for Diagnostic and Statistical Manual&#xD;
             (DSM)-V (SCID) or diagnostic interview with a trained clinician.&#xD;
&#xD;
          7. Stable medication regimen over at least the past two weeks, including the use of&#xD;
             either an oral or intramuscular administration of an antipsychotic medication.&#xD;
             Additionally, subjects may take any prescribed medication aside from a&#xD;
             nicotine-containing product as long as it has been regularly taken over the past two&#xD;
             weeks, including as-needed (&quot;PRN&quot;) medication.&#xD;
&#xD;
          8. Negative urine toxicology and negative urine cotinine (to confirm no recent nicotine&#xD;
             use) at screening.&#xD;
&#xD;
          9. Does not meet criteria for substance or alcohol use disorder per the SCID over the&#xD;
             past 6 months&#xD;
&#xD;
         10. For females, no longer of child-bearing potential, or agreeing to practice effective&#xD;
             contraception during the study (e.g., established use of oral, injected or implanted&#xD;
             hormonal methods of contraception; placement of an intrauterine device [IUD] or&#xD;
             intrauterine system [IUS]; barrier methods: condom with spermicidal&#xD;
             foam/gel/film/cream/suppository or occlusive cap [diaphragm or cervical/vault caps]&#xD;
             with spermicidal foam/gel/film/cream/suppository; male partner sterilization; or true&#xD;
             abstinence when this is in line with the preferred and usual lifestyle of the&#xD;
             subject); and,&#xD;
&#xD;
         11. For females of child-bearing potential, must have negative urine pregnancy test at&#xD;
             time of screening visit and before each testing day.&#xD;
&#xD;
         12. Not breastfeeding/nursing at time of screening or at any time during the study.&#xD;
&#xD;
        Exclusion Criteria for schizophrenia subjects:&#xD;
&#xD;
          1. Age less than 18 or greater than 65.&#xD;
&#xD;
          2. Not communicative in English.&#xD;
&#xD;
          3. Unable to provide written informed consent.&#xD;
&#xD;
          4. Active suicidal ideation or suicidal behavior.&#xD;
&#xD;
          5. Current, unstable medical or neurological illness or significant abnormality on ECG.&#xD;
&#xD;
          6. History of severe head trauma.&#xD;
&#xD;
          7. BMI &lt; 17.5 or &gt; 45.&#xD;
&#xD;
          8. History of allergy to transdermal patches.&#xD;
&#xD;
          9. Screening visit resting heart rate &gt; 110 or &lt; 50 beats per minute, or known history of&#xD;
             clinically significant cardiac rhythm abnormalities.&#xD;
&#xD;
         10. Screening visit systolic blood pressure &gt; 160 or &lt; 90, or diastolic blood pressure &gt;&#xD;
             95 or &lt; 50.&#xD;
&#xD;
         11. Positive urine toxicology or positive urine cotinine during screening.&#xD;
&#xD;
         12. Meets criteria for diagnosis of substance or alcohol use disorder by SCID within the&#xD;
             past 6 months.&#xD;
&#xD;
         13. Reports any tobacco smoking or nicotine use over the past month.&#xD;
&#xD;
         14. Not taking an antipsychotic medication.&#xD;
&#xD;
         15. Positive urine pregnancy test at time of screening, before each testing day, or any&#xD;
             potential concern for pregnancy at any time during the study&#xD;
&#xD;
         16. Breastfeeding/nursing at time of screening or at any time during the study.&#xD;
&#xD;
        Inclusion Criteria for healthy volunteer subjects:&#xD;
&#xD;
        All of the above except for subjects will be psychiatrically healthy and not taking&#xD;
        psychotropic or potentially psychoactive prescription medication.&#xD;
&#xD;
        Exclusion Criteria for healthy volunteer subjects:&#xD;
&#xD;
        All of the above and in addition:&#xD;
&#xD;
          1. Current use of psychotropic or potentially psychoactive prescription medication.&#xD;
&#xD;
          2. Major psychiatric disorder as determined by DSM-5 (schizophrenia, major depression,&#xD;
             bipolar disorder, obsessive-compulsive disorder, post-traumatic stress disorder, etc.)&#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>Alan S Lewis, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt Psychiatric Hospital</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Krakowski MI, De Sanctis P, Foxe JJ, Hoptman MJ, Nolan K, Kamiel S, Czobor P. Disturbances in Response Inhibition and Emotional Processing as Potential Pathways to Violence in Schizophrenia: A High-Density Event-Related Potential Study. Schizophr Bull. 2016 Jul;42(4):963-74. doi: 10.1093/schbul/sbw005. Epub 2016 Feb 19.</citation>
    <PMID>26895845</PMID>
  </reference>
  <reference>
    <citation>Egashira K, Matsuo K, Nakashima M, Watanuki T, Harada K, Nakano M, Matsubara T, Takahashi K, Watanabe Y. Blunted brain activation in patients with schizophrenia in response to emotional cognitive inhibition: a functional near-infrared spectroscopy study. Schizophr Res. 2015 Mar;162(1-3):196-204. doi: 10.1016/j.schres.2014.12.038. Epub 2015 Jan 13.</citation>
    <PMID>25595654</PMID>
  </reference>
  <reference>
    <citation>Lewis AS, van Schalkwyk GI, Lopez MO, Volkmar FR, Picciotto MR, Sukhodolsky DG. An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder. J Autism Dev Disord. 2018 Aug;48(8):2748-2757. doi: 10.1007/s10803-018-3536-7.</citation>
    <PMID>29536216</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>February 7, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <results_first_submitted>December 20, 2021</results_first_submitted>
  <results_first_submitted_qc>April 27, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">April 29, 2022</results_first_posted>
  <last_update_submitted>April 27, 2022</last_update_submitted>
  <last_update_submitted_qc>April 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
    <investigator_full_name>Alan Lewis</investigator_full_name>
    <investigator_title>Assistant Professor of Psychiatry and Behavioral Sciences</investigator_title>
  </responsible_party>
  <keyword>Nicotine</keyword>
  <keyword>Nicotinic acetylcholine receptors</keyword>
  <keyword>Schizophrenia</keyword>
  <keyword>Schizoaffective disorder</keyword>
  <keyword>Healthy control</keyword>
  <keyword>Impulsive behavior</keyword>
  <keyword>Aggression</keyword>
  <keyword>Urgency</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Impulsive Behavior</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nicotine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 23, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/84/NCT03838484/Prot_SAP_004.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 23, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/84/NCT03838484/ICF_005.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>1 participant lost to follow-up</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Healthy: Placebo First, Nicotine Last</title>
          <description>Healthy controls will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
        </group>
        <group group_id="P2">
          <title>Healthy: Nicotine First, Placebo Last</title>
          <description>Healthy controls will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
        </group>
        <group group_id="P3">
          <title>SCZ: Placebo First, Nicotine Last</title>
          <description>Subjects with schizophrenia (SCZ) will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
        </group>
        <group group_id="P4">
          <title>SCZ: Nicotine First, Placebo Last</title>
          <description>Subjects with schizophrenia (SCZ) will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Healthy: Placebo First, Nicotine Last</title>
          <description>Healthy controls will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
        </group>
        <group group_id="B2">
          <title>Healthy: Nicotine First, Placebo Last</title>
          <description>Healthy controls will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
        </group>
        <group group_id="B3">
          <title>SCZ: Placebo First, Nicotine Last</title>
          <description>Subjects with schizophrenia (SCZ) will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
        </group>
        <group group_id="B4">
          <title>SCZ: Nicotine First, Placebo Last</title>
          <description>Subjects with schizophrenia (SCZ) will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="4"/>
            <count group_id="B4" value="4"/>
            <count group_id="B5" value="17"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29" spread="4"/>
                    <measurement group_id="B2" value="38" spread="11"/>
                    <measurement group_id="B3" value="33" spread="15"/>
                    <measurement group_id="B4" value="26" spread="5"/>
                    <measurement group_id="B5" value="33" spread="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>False Alarm Error Rate</title>
        <description>Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key (&quot;Go&quot;) or withhold pressing a key (&quot;NoGo&quot;). The False Alarm Error Rate will be measured by the proportion of incorrect responses.</description>
        <time_frame>Week 1</time_frame>
        <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 1. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy: Placebo</title>
            <description>Healthy controls will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
          <group group_id="O2">
            <title>Healthy: Nicotine</title>
            <description>Healthy controls will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
          <group group_id="O3">
            <title>SCZ: Placebo</title>
            <description>Subjects with schizophrenia (SCZ) will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
          <group group_id="O4">
            <title>SCZ: Nicotine</title>
            <description>Subjects with schizophrenia (SCZ) will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
        </group_list>
        <measure>
          <title>False Alarm Error Rate</title>
          <description>Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key (&quot;Go&quot;) or withhold pressing a key (&quot;NoGo&quot;). The False Alarm Error Rate will be measured by the proportion of incorrect responses.</description>
          <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 1. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 1.</population>
          <units>Proportion of incorrect responses</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.20" spread="0.05"/>
                    <measurement group_id="O2" value="0.15" spread="0.07"/>
                    <measurement group_id="O3" value="0.11" spread="0.04"/>
                    <measurement group_id="O4" value="0.19" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>False Alarm Error Rate</title>
        <description>Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key (&quot;Go&quot;) or withhold pressing a key (&quot;NoGo&quot;). The False Alarm Error Rate will be measured by the proportion of incorrect responses.</description>
        <time_frame>Week 2</time_frame>
        <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 2. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy: Nicotine</title>
            <description>Healthy controls will apply nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
          <group group_id="O2">
            <title>Healthy: Placebo</title>
            <description>Healthy controls will apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
          <group group_id="O3">
            <title>SCZ: Nicotine</title>
            <description>Subjects with schizophrenia (SCZ) will apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
          <group group_id="O4">
            <title>SCZ: Placebo</title>
            <description>Subjects with schizophrenia (SCZ) will apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
        </group_list>
        <measure>
          <title>False Alarm Error Rate</title>
          <description>Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key (&quot;Go&quot;) or withhold pressing a key (&quot;NoGo&quot;). The False Alarm Error Rate will be measured by the proportion of incorrect responses.</description>
          <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 2. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 2.</population>
          <units>Proportion of incorrect responses</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.18" spread="0.03"/>
                    <measurement group_id="O2" value="0.13" spread="0.06"/>
                    <measurement group_id="O3" value="0.15" spread="0.02"/>
                    <measurement group_id="O4" value="0.23" spread="0.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Omission Error Rate</title>
        <description>Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key (&quot;Go&quot;) or withhold pressing a key (&quot;NoGo&quot;). The Omission Error Rate will be measured by the proportion of questions asked with a failure to respond.</description>
        <time_frame>Week 1</time_frame>
        <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 1. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy: Placebo</title>
            <description>Healthy controls will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
          <group group_id="O2">
            <title>Healthy: Nicotine</title>
            <description>Healthy controls will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
          <group group_id="O3">
            <title>SCZ: Placebo</title>
            <description>Subjects with schizophrenia (SCZ) will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
          <group group_id="O4">
            <title>SCZ: Nicotine</title>
            <description>Subjects with schizophrenia (SCZ) will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Omission Error Rate</title>
          <description>Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key (&quot;Go&quot;) or withhold pressing a key (&quot;NoGo&quot;). The Omission Error Rate will be measured by the proportion of questions asked with a failure to respond.</description>
          <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 1. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 1.</population>
          <units>Proportion of omitted responses</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.24" spread="0.04"/>
                    <measurement group_id="O2" value="0.29" spread="0.06"/>
                    <measurement group_id="O3" value="0.44" spread="0.06"/>
                    <measurement group_id="O4" value="0.27" spread="0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Omission Error Rate</title>
        <description>Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key (&quot;Go&quot;) or withhold pressing a key (&quot;NoGo&quot;). The Omission Error Rate will be measured by the proportion of questions asked with a failure to respond.</description>
        <time_frame>Week 2</time_frame>
        <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 2. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy: Nicotine</title>
            <description>Healthy controls will apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
          <group group_id="O2">
            <title>Healthy: Placebo</title>
            <description>Healthy controls will apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
          <group group_id="O3">
            <title>SCZ: Nicotine</title>
            <description>Subjects with schizophrenia (SCZ) will apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
          <group group_id="O4">
            <title>SCZ: Placebo</title>
            <description>Subjects with schizophrenia (SCZ) will apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Omission Error Rate</title>
          <description>Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key (&quot;Go&quot;) or withhold pressing a key (&quot;NoGo&quot;). The Omission Error Rate will be measured by the proportion of questions asked with a failure to respond.</description>
          <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 2. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 2.</population>
          <units>Proportion of omitted responses</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.29" spread="0.07"/>
                    <measurement group_id="O2" value="0.23" spread="0.06"/>
                    <measurement group_id="O3" value="0.38" spread="0.10"/>
                    <measurement group_id="O4" value="0.30" spread="0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Reaction Time for Correct Hits</title>
        <description>Time taken from stimulus presentation to button push during Go trials</description>
        <time_frame>Week 1</time_frame>
        <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 1. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy: Placebo</title>
            <description>Healthy controls will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
          <group group_id="O2">
            <title>Healthy: Nicotine</title>
            <description>Healthy controls will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
          <group group_id="O3">
            <title>SCZ: Placebo</title>
            <description>Subjects with schizophrenia (SCZ) will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
          <group group_id="O4">
            <title>SCZ: Nicotine</title>
            <description>Subjects with schizophrenia (SCZ) will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Reaction Time for Correct Hits</title>
          <description>Time taken from stimulus presentation to button push during Go trials</description>
          <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 1. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 1.</population>
          <units>Milliseconds</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="485.09" spread="16.56"/>
                    <measurement group_id="O2" value="491.05" spread="16.50"/>
                    <measurement group_id="O3" value="468.96" spread="13.49"/>
                    <measurement group_id="O4" value="517.05" spread="4.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Reaction Time for Correct Hits</title>
        <description>Time taken from stimulus presentation to button push during Go trials</description>
        <time_frame>Week 2</time_frame>
        <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 2. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy: Nicotine</title>
            <description>Healthy controls will apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
          <group group_id="O2">
            <title>Healthy: Placebo</title>
            <description>Healthy controls will apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
          <group group_id="O3">
            <title>SCZ: Nicotine</title>
            <description>Subjects with schizophrenia (SCZ) will apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
          <group group_id="O4">
            <title>SCZ: Placebo</title>
            <description>Subjects with schizophrenia (SCZ) will apply placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Reaction Time for Correct Hits</title>
          <description>Time taken from stimulus presentation to button push during Go trials</description>
          <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 2. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 2.</population>
          <units>Milliseconds</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="477.54" spread="15.06"/>
                    <measurement group_id="O2" value="511.10" spread="10.88"/>
                    <measurement group_id="O3" value="478.99" spread="18.36"/>
                    <measurement group_id="O4" value="490.67" spread="24.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Reaction Time for False Alarms</title>
        <description>Time taken from stimulus presentation to button push during NoGo trials</description>
        <time_frame>Week 1</time_frame>
        <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 1. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy: Placebo</title>
            <description>Healthy controls will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
          <group group_id="O2">
            <title>Healthy: Nicotine</title>
            <description>Healthy controls will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
          <group group_id="O3">
            <title>SCZ: Placebo</title>
            <description>Subjects with schizophrenia (SCZ) will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
          <group group_id="O4">
            <title>SCZ: Nicotine</title>
            <description>Subjects with schizophrenia (SCZ) will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Reaction Time for False Alarms</title>
          <description>Time taken from stimulus presentation to button push during NoGo trials</description>
          <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 1. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 1.</population>
          <units>Milliseconds</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="718.89" spread="36.52"/>
                    <measurement group_id="O2" value="658.20" spread="40.50"/>
                    <measurement group_id="O3" value="813.00" spread="48.83"/>
                    <measurement group_id="O4" value="692.95" spread="31.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Reaction Time for False Alarms</title>
        <description>Time taken from stimulus presentation to button push during NoGo trials</description>
        <time_frame>Week 2</time_frame>
        <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 2. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Healthy: Nicotine</title>
            <description>Healthy controls will apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
          <group group_id="O2">
            <title>Healthy: Placebo</title>
            <description>Healthy controls will apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
          <group group_id="O3">
            <title>SCZ: Nicotine</title>
            <description>Subjects with schizophrenia (SCZ) will apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
          <group group_id="O4">
            <title>SCZ: Placebo</title>
            <description>Subjects with schizophrenia (SCZ) will apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Reaction Time for False Alarms</title>
          <description>Time taken from stimulus presentation to button push during NoGo trials</description>
          <population>Please note that this outcome measure specifically refers to the specified outcome measure time frame: week 2. Because this is a crossover trial, only a subset of the subjects completed each treatment (placebo or nicotine) during week 2.</population>
          <units>Milliseconds</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="727.30" spread="60.81"/>
                    <measurement group_id="O2" value="758.12" spread="69.68"/>
                    <measurement group_id="O3" value="769.95" spread="42.67"/>
                    <measurement group_id="O4" value="703.99" spread="23.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>30 minutes following removal of patch on each session day.</time_frame>
      <desc>Adverse event information was collected for any untoward or unfavorable medical occurrence in a participant using the Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale autonomic subscale score. Adverse events were collected from the time the consent was signed through participant completion.</desc>
      <group_list>
        <group group_id="E1">
          <title>Healthy: Placebo</title>
          <description>Healthy controls will apply placebo skin patch for up to two hours prior to behavioral and EEG task.</description>
        </group>
        <group group_id="E2">
          <title>Healthy: Nicotine</title>
          <description>Healthy controls will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task.</description>
        </group>
        <group group_id="E3">
          <title>SCZ: Placebo</title>
          <description>Subjects with schizophrenia (SCZ) will apply placebo skin patch for up to two hours prior to behavioral and EEG task.</description>
        </group>
        <group group_id="E4">
          <title>SCZ: Nicotine</title>
          <description>Subjects with schizophrenia (SCZ) will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Heart palpitations</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurry vision</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Increased salivation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Increased urination</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Sweating</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Recruitment for this study did not reach its original intended size due to difficulties from the Covid19 pandemic.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Alan S. Lewis, M.D., Ph.D.</name_or_title>
      <organization>Vanderbilt University Medical Center</organization>
      <phone>615-875-4027</phone>
      <email>alan.s.lewis@vumc.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03838484
org study id: 190021
secondary id: 7K23MH116339
nct id: NCT03838484
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purpose of this study is to test whether nicotine, a drug that activates receptors called
      nicotinic acetylcholine receptors in the brain, improves the ability to make or withhold
      responses to faces that are either emotionally neutral or emotionally negative. This study
      will also test whether the drug affects brain activity while making or withholding responses
      using electroencephalography. Previous studies in people with schizophrenia have shown that
      more errors in response to negative emotional cues are related to greater likelihood of
      impulsive aggressive behavior. Therefore, the aim of this study is to determine whether
      nicotine might be a new strategy to reduce aggressive behavior. The investigators' goal is 25
      individuals with schizophrenia and 25 healthy controls to complete the study at Vanderbilt.
This human laboratory study seeks to test the hypothesis that activation of nicotinic
      acetylcholine receptors (nAChRs) in the brain will reduce impulsive behavior in response to
      negative emotional cues as compared to neutral emotional cues. Because impulsive action
      during negative mood states is strongly correlated with impulsive aggression in both healthy
      individuals and individuals with schizophrenia (discussed below), the investigators'
      overarching, long-term goal is to determine whether nAChRs in general as well as specific
      nAChR subclasses might represent novel treatment targets to reduce impulsive aggressive
      behavior, a significant public health problem.

      Nicotinic acetylcholine receptors are a large family of excitatory, pentameric, ionotropic,
      ligand-gated ion channels located throughout the brain and the remainder of the body. Their
      endogenous ligand is acetylcholine, yet this family is defined by their common activation by
      nicotine. Interestingly, anti-aggressive, or "serenic" effects of nicotine have been
      demonstrated across a number of animal models, including mice, rats, and non-human primates,
      and multiple human laboratory studies demonstrate an anti-aggressive effect of nicotine in
      humans. The investigators' laboratory has also demonstrated that acute administration of
      nicotine at relatively low doses results in reduction of aggressive behaviors in mouse
      models. Because nicotine is active at all nAChRs, the investigators explored this mechanism
      further and found that hippocampal alpha-7 nAChRs were both necessary and sufficient for
      nicotine's serenic effect. Consistent with these findings, there is substantial evidence in
      humans that reduction of alpha-7 nAChR signaling enhances aggressive behavior, including in
      individuals with 15q13.3 microdeletion syndrome, a genetic disorder resulting from the
      deletion of the region of chromosome 15 containing the gene coding for alpha-7 nAChRs. The
      investigators have also translated these findings into human clinical populations, finding
      recently the safety and efficacy of transdermal nicotine to reduce aggression and
      irritability in young adults with autism spectrum disorder. This work, along with other
      previous case studies in humans, supports targeting nAChRs using transdermal nicotine to
      reduce aggressive behaviors.

      Urgency is a behavioral construct defined as the tendency to act rashly in the context of
      strong positive or negative emotion, and explains a large degree of variance in the
      development of impulsive aggression in subjects with schizophrenia and other populations
      without psychiatric disorders. In patients with schizophrenia, degree of urgency correlates
      with structural and functional changes in a neuronal network involving prefrontal cortical
      and limbic/cognitive control brain regions. A number of previous studies have similarly
      demonstrated impulsivity in the context of negative emotion, called "negative urgency",
      correlates with history of aggression, as well as substance use and other risky behaviors.
      Urgency is a hereditable trait that may be considered an endophenotype of impulsive
      aggression.

      Recent studies in humans have explored the relationship between mood-related impulsivity
      (i.e. urgency) and aggressive behavior using an Emotional Go/NoGo task. This task measures
      responding or response withholding to visual stimuli of neutral or emotional (typically
      negative) valence, and quantifies reaction time and commission/omission errors as a function
      of stimulus valence. Using an Emotional Go/NoGo task, Krakowski et al. studied healthy
      controls, patients with schizophrenia with or without a history of violence, and
      non-psychotic individuals with history of violence. In all groups, emotional valence had a
      significant effect on error commission. In schizophrenia patients, individuals with history
      of violence were significantly faster to make an incorrect response to negative stimuli (i.e.
      not withhold a response) than patients without history of violence, whereas the two groups
      did not differ in response times to neutral valence stimuli. Other studies have also
      demonstrated an interaction between emotional valence and impulsive errors in schizophrenia,
      as well as a relationship between emotional valence, impulsive errors, history of violence,
      and frontal cortex 5-HT1B receptor binding.

      While the investigators' studies in mice suggest a direct effect of nAChR stimulation on
      aggression through activation of the alpha-7 nAChR and are supported by the results using
      transdermal nicotine in humans, to the investigators' knowledge no previous studies have
      directly examined the relationship between pharmacological targeting of nAChRs using
      transdermal nicotine and effects on impulsivity in the context of emotional cues in humans.
      The investigators now aim to directly test this hypothesis using an Emotional Go/NoGo task in
      subjects with schizophrenia and healthy controls to determine whether transdermal nicotine
      improves impulsive behavior and neural correlates in the context of negative and neutral
      valence cues. Given the relationship between impulsivity and aggressive behavior, the
      findings of this proposed study will strongly inform future studies of targeting nAChRs
      broadly and alpha-7 nAChRs more specifically to identify novel treatments for individuals
      with severe neuropsychiatric disorders struggling with persistent pathological impulsive
      aggression.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: False Alarm Error Rate
time frame: Week 1
description: Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key ("Go") or withhold pressing a key ("NoGo"). The False Alarm Error Rate will be measured by the proportion of incorrect responses.
measure: False Alarm Error Rate
time frame: Week 2
description: Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key ("Go") or withhold pressing a key ("NoGo"). The False Alarm Error Rate will be measured by the proportion of incorrect responses.
measure: Omission Error Rate
time frame: Week 1
description: Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key ("Go") or withhold pressing a key ("NoGo"). The Omission Error Rate will be measured by the proportion of questions asked with a failure to respond.
measure: Omission Error Rate
time frame: Week 2
description: Participants will be shown fearful, sad, angry, and disgust faces (negative valence) and neutral faces performed in 5 blocks (3 emotional blocks with angry/fearful/sad/disgust faces and 2 non-emotional blocks). In each block the subject is instructed on the go/no-go targets and will press a key ("Go") or withhold pressing a key ("NoGo"). The Omission Error Rate will be measured by the proportion of questions asked with a failure to respond.
measure: Reaction Time for Correct Hits
time frame: Week 1
description: Time taken from stimulus presentation to button push during Go trials
measure: Reaction Time for Correct Hits
time frame: Week 2
description: Time taken from stimulus presentation to button push during Go trials
measure: Reaction Time for False Alarms
time frame: Week 1
description: Time taken from stimulus presentation to button push during NoGo trials
measure: Reaction Time for False Alarms
time frame: Week 2
description: Time taken from stimulus presentation to button push during NoGo trials
arm group label: Healthy: placebo first, nicotine last
arm group type: Experimental
description: Healthy controls will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.
arm group label: Healthy: nicotine first, placebo last
arm group type: Experimental
description: Healthy controls will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.
arm group label: SCZ: placebo first, nicotine last
arm group type: Experimental
description: Subjects with schizophrenia (SCZ) will apply placebo skin patch for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a nicotine patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the second visit in week 2.
arm group label: SCZ: nicotine first, placebo last
arm group type: Experimental
description: Subjects with schizophrenia (SCZ) will apply nicotine skin patch (7 mg/24 hour dose) for up to two hours prior to behavioral and EEG task during the first visit in week 1. After a washout period, they will return and apply a placebo patch for up to two hours prior to behavioral and EEG task during the second visit in week 2.
intervention type: Drug
intervention name: Nicotine Patch, 7 Mg/24 Hr
description: Nicotine patch, 7 mg/24 hour will be applied to the skin.
arm group label: Healthy: nicotine first, placebo last
arm group label: Healthy: placebo first, nicotine last
arm group label: SCZ: nicotine first, placebo last
arm group label: SCZ: placebo first, nicotine last
intervention type: Drug
intervention name: Placebo patch
description: Placebo skin patch will be applied to the skin.
arm group label: Healthy: nicotine first, placebo last
arm group label: Healthy: placebo first, nicotine last
arm group label: SCZ: nicotine first, placebo last
arm group label: SCZ: placebo first, nicotine last
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Alan S Lewis, MD, PhD
role: Principal Investigator
affiliation: Vanderbilt University Medical Center
facility: 
country: United States
citation: Krakowski MI, De Sanctis P, Foxe JJ, Hoptman MJ, Nolan K, Kamiel S, Czobor P. Disturbances in Response Inhibition and Emotional Processing as Potential Pathways to Violence in Schizophrenia: A High-Density Event-Related Potential Study. Schizophr Bull. 2016 Jul;42(4):963-74. doi: 10.1093/schbul/sbw005. Epub 2016 Feb 19.
PMID: 26895845
citation: Egashira K, Matsuo K, Nakashima M, Watanuki T, Harada K, Nakano M, Matsubara T, Takahashi K, Watanabe Y. Blunted brain activation in patients with schizophrenia in response to emotional cognitive inhibition: a functional near-infrared spectroscopy study. Schizophr Res. 2015 Mar;162(1-3):196-204. doi: 10.1016/j.schres.2014.12.038. Epub 2015 Jan 13.
PMID: 25595654
citation: Lewis AS, van Schalkwyk GI, Lopez MO, Volkmar FR, Picciotto MR, Sukhodolsky DG. An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder. J Autism Dev Disord. 2018 Aug;48(8):2748-2757. doi: 10.1007/s10803-018-3536-7.
PMID: 29536216
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University Medical Center
investigator full name: Alan Lewis
investigator title: Assistant Professor of Psychiatry and Behavioral Sciences
mesh term: Schizophrenia
mesh term: Impulsive Behavior
mesh term: Nicotine
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Recruitment for this study did not reach its original intended size due to difficulties from the Covid19 pandemic.
point of contact: 