<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/NCT03033056</url>
  </required_header>
  <id_info>
    <org_study_id>1610M96641</org_study_id>
    <nct_id>NCT03033056</nct_id>
  </id_info>
  <brief_title>Neurobiology of Generalized Fear-Conditioning &amp; Avoidance in Anxiety Disorders</brief_title>
  <official_title>Neurobiology of Generalized Fear-Conditioning &amp; Avoidance in Anxiety Disorders (Community Anxiety Response Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Minnesota</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Anxiety disorders are among the most prevalent, costly, and disabling mental illnesses. One&#xD;
      central, yet largely understudied, abnormality in anxiety disorders is the heightened&#xD;
      tendency to display fear and avoidance in reaction to benign or safe events that resemble&#xD;
      feared situations. The current project maps brain circuits associated with this abnormality&#xD;
      in order to contribute to future brain-based diagnosis and treatments for clinical anxiety.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of this project is to neurally, behaviorally, psychologically, and clinically&#xD;
      characterize fundamental Pavlovian and instrumental dimensions of potential threat through&#xD;
      which emotional and behavioral responses to threat cues generalize to resembling, safe&#xD;
      stimuli. Such generalization is aligned with the potential threat construct due to the threat&#xD;
      ambiguity, or uncertain threat value, inherent in these safe 'generalization' stimuli. The&#xD;
      Pavlovian dimension of interest is generalization of conditioned fear: a fundamental&#xD;
      Pavlovian process through which fear transfers, or generalizes, to safe stimuli resembling a&#xD;
      conditioned threat-cue (CS+). The targeted instrumental dimension is generalized avoidance:&#xD;
      active decisions to withdraw from safe stimuli resembling the CS+ that are motivationally&#xD;
      prompted by Pavlovian generalization. Given lab-based findings have linked heightened&#xD;
      Pavlovian generalization to a variety of traditional anxiety disorders, overgeneralization&#xD;
      represents a promising dimension of potential threat with relevance across traditional&#xD;
      anxiety disorders. One central aspect of this project is testing personality and psychiatric&#xD;
      factors (e.g., trait fear, internalizing, externalizing) that may account for the relevance&#xD;
      of generalization and its neurobiology across traditional anxiety disorders. A second key&#xD;
      aspect, is studying neural processes by which Pavlovian generalization evokes instrumental&#xD;
      generalized avoidance of benign stimuli (resembling danger cues), which, when excessive, is&#xD;
      likely to impair day-to-day functioning in anxiety patients. Unfortunately, human&#xD;
      fear-conditioning experiments in clinical samples, have focused almost exclusively on&#xD;
      passive-emotional, Pavlovian conditioning, to the virtual exclusion of studying&#xD;
      active-behavioral, instrumental avoidance. The current neuroimaging project fills this gap by&#xD;
      applying a novel Pavlovian-instrumental generalization paradigm to neurally and behaviorally&#xD;
      elucidate Pavlovian processes leading to generalized instrumental avoidance. Personality&#xD;
      moderators (e.g., dispositional resilience) of relations between Pavlovian and instrumental&#xD;
      generalization will also be examined. The studied adult samples will display a wide range of&#xD;
      symptom severity across traditional anxiety disorders and will include anxiety-clinic&#xD;
      patients and healthy comparisons (N=159). Central goals of this proposal include: 1)&#xD;
      elucidating the neurobiology of Pavlovian and instrumental generalization and their&#xD;
      interaction, 2) testing relations between neural substrates of Pavlovian and instrumental&#xD;
      generalization and broad psychiatric dysfunction (Aims2-3); and 3) assessing the degree to&#xD;
      which relations between these dimensions of generalization and broad dysfunction are driven&#xD;
      by psychometrically validated personality traits relevant across traditional anxiety&#xD;
      disorders. This third and final goal is critical to the project, because individual&#xD;
      difference measures capturing empirically-validated psychological constructs will likely&#xD;
      track relations between fundamental conditioning processes (e.g., generalization) and general&#xD;
      dysfunction, better than traditional, polythetic, diagnostic entities, that, by and large, do&#xD;
      not reflect any single coherent psychological process.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 17, 2017</start_date>
  <completion_date type="Actual">August 1, 2021</completion_date>
  <primary_completion_date type="Actual">August 1, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Functional magnetic resonance imaging</measure>
    <time_frame>Years 1-4</time_frame>
    <description>Blood oxygenation level dependent responses elicited during the fear conditioning paradigm</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Behavioral measures</measure>
    <time_frame>Years 1-4</time_frame>
    <description>Online behavioral responses elicited during the fear conditioning paradigm</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">208</enrollment>
  <condition>Anxiety Disorders</condition>
  <arm_group>
    <arm_group_label>Anxiety Clinic Patients</arm_group_label>
    <description>Adult males and females being treated at the anxiety disorders clinic at the University of Minnesota predominantly for clinical anxiety.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Comparisons</arm_group_label>
    <description>Sex, age, and socioeconomically matched healthy controls</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Test of fear conditioning</intervention_name>
    <description>Behavioral and brain correlates of conditioned fear generalization and avoidance will be assessed using fMRI and related to levels of anxiety related psychopathology.</description>
    <arm_group_label>Anxiety Clinic Patients</arm_group_label>
    <arm_group_label>Healthy Comparisons</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Male and female adults presenting with anxiety symptoms at the Anxiety Disorders Clinic in&#xD;
        the Department of Psychiatry at U of MN, as well as demographically matched healthy&#xD;
        comparisons&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        A. Diagnosis: No psychiatric diagnosis is required, but recruitment will be guided by the&#xD;
        goal of attaining a sample with wide-ranging levels of both anxiety symptom severity and&#xD;
        individual differences in anxiety-related states and traits.&#xD;
&#xD;
        B. Caffeine and tobacco use: Participants will abstain from caffeine and tobacco one hour&#xD;
        preceding testing&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        A. Psychiatric health: Current or past history of any psychotic disorder, bipolar disorder,&#xD;
        delirium, dementia, amnestic disorder, or mental retardation; comorbid depression if&#xD;
        accompanied by current, significant suicide risk; substance use disorder presently or for&#xD;
        the six months preceding testing.&#xD;
&#xD;
        B. Current use of any medication that alters central nervous system function including&#xD;
        antidepressants, benzodiazepines, anti-psychotics, mood stabilizers,anti-parkinsonian&#xD;
        agents, anti-convulsants, sleep medications, pain medications, and anti-hypertensives.&#xD;
&#xD;
        C. Medical health: Current or past medical illnesses which in the investigator's opinion&#xD;
        may confound study results, or place the participant at risk.&#xD;
&#xD;
        D. Pregnancy status: Females who are, or may be, pregnant. Recruitment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shmuel Lissek, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>U of MN</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of MInnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>March 9, 2022</last_update_submitted>
  <last_update_submitted_qc>March 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>fear-conditioning</keyword>
  <keyword>behavioral avoidance</keyword>
  <keyword>anxiety disorders</keyword>
  <keyword>fMRI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anxiety Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03033056
org study id: 1610M96641
nct id: NCT03033056
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Anxiety disorders are among the most prevalent, costly, and disabling mental illnesses. One
      central, yet largely understudied, abnormality in anxiety disorders is the heightened
      tendency to display fear and avoidance in reaction to benign or safe events that resemble
      feared situations. The current project maps brain circuits associated with this abnormality
      in order to contribute to future brain-based diagnosis and treatments for clinical anxiety.
The objective of this project is to neurally, behaviorally, psychologically, and clinically
      characterize fundamental Pavlovian and instrumental dimensions of potential threat through
      which emotional and behavioral responses to threat cues generalize to resembling, safe
      stimuli. Such generalization is aligned with the potential threat construct due to the threat
      ambiguity, or uncertain threat value, inherent in these safe 'generalization' stimuli. The
      Pavlovian dimension of interest is generalization of conditioned fear: a fundamental
      Pavlovian process through which fear transfers, or generalizes, to safe stimuli resembling a
      conditioned threat-cue (CS+). The targeted instrumental dimension is generalized avoidance:
      active decisions to withdraw from safe stimuli resembling the CS+ that are motivationally
      prompted by Pavlovian generalization. Given lab-based findings have linked heightened
      Pavlovian generalization to a variety of traditional anxiety disorders, overgeneralization
      represents a promising dimension of potential threat with relevance across traditional
      anxiety disorders. One central aspect of this project is testing personality and psychiatric
      factors (e.g., trait fear, internalizing, externalizing) that may account for the relevance
      of generalization and its neurobiology across traditional anxiety disorders. A second key
      aspect, is studying neural processes by which Pavlovian generalization evokes instrumental
      generalized avoidance of benign stimuli (resembling danger cues), which, when excessive, is
      likely to impair day-to-day functioning in anxiety patients. Unfortunately, human
      fear-conditioning experiments in clinical samples, have focused almost exclusively on
      passive-emotional, Pavlovian conditioning, to the virtual exclusion of studying
      active-behavioral, instrumental avoidance. The current neuroimaging project fills this gap by
      applying a novel Pavlovian-instrumental generalization paradigm to neurally and behaviorally
      elucidate Pavlovian processes leading to generalized instrumental avoidance. Personality
      moderators (e.g., dispositional resilience) of relations between Pavlovian and instrumental
      generalization will also be examined. The studied adult samples will display a wide range of
      symptom severity across traditional anxiety disorders and will include anxiety-clinic
      patients and healthy comparisons (N=159). Central goals of this proposal include: 1)
      elucidating the neurobiology of Pavlovian and instrumental generalization and their
      interaction, 2) testing relations between neural substrates of Pavlovian and instrumental
      generalization and broad psychiatric dysfunction (Aims2-3); and 3) assessing the degree to
      which relations between these dimensions of generalization and broad dysfunction are driven
      by psychometrically validated personality traits relevant across traditional anxiety
      disorders. This third and final goal is critical to the project, because individual
      difference measures capturing empirically-validated psychological constructs will likely
      track relations between fundamental conditioning processes (e.g., generalization) and general
      dysfunction, better than traditional, polythetic, diagnostic entities, that, by and large, do
      not reflect any single coherent psychological process.
observational model: Case-Control
time perspective: Prospective
measure: Functional magnetic resonance imaging
time frame: Years 1-4
description: Blood oxygenation level dependent responses elicited during the fear conditioning paradigm
measure: Behavioral measures
time frame: Years 1-4
description: Online behavioral responses elicited during the fear conditioning paradigm
arm group label: Anxiety Clinic Patients
description: Adult males and females being treated at the anxiety disorders clinic at the University of Minnesota predominantly for clinical anxiety.
arm group label: Healthy Comparisons
description: Sex, age, and socioeconomically matched healthy controls
intervention type: Behavioral
intervention name: Test of fear conditioning
description: Behavioral and brain correlates of conditioned fear generalization and avoidance will be assessed using fMRI and related to levels of anxiety related psychopathology.
arm group label: Anxiety Clinic Patients
arm group label: Healthy Comparisons
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Shmuel Lissek, PhD
role: Principal Investigator
affiliation: U of MN
facility: 
country: United States
responsible party type: Sponsor
mesh term: Anxiety Disorders
sharing ipd: No