<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/NCT01733030</url>
  </required_header>
  <id_info>
    <org_study_id>MH080130</org_study_id>
    <nct_id>NCT01733030</nct_id>
  </id_info>
  <brief_title>The Effects of D-cycloserine on Stimulus Generalization of Conditioned Fear Healthy Controls.</brief_title>
  <acronym>DCS</acronym>
  <official_title>The Effects of D-cycloserine on Stimulus Generalization of Conditioned Fear in Healthy Controls.</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      PROJECT SUMMARY:&#xD;
&#xD;
      PTSD is a debilitating psychiatric condition precipitated by exposure to extreme, or life&#xD;
      threatening, trauma with an estimated lifetime prevalence between 8% and 9% in U.S. adults.&#xD;
      One core symptom of PTSD is intense psychological distress in the presence of stimuli that&#xD;
      &quot;resemble&quot; one or more aspects of the trauma experience (DSM-IV). This phenomenon referred to&#xD;
      as stimulus generalization has received surprisingly little empirical testing in the context&#xD;
      of clinical anxiety in general, and PTSD more specifically. The current proposal represents&#xD;
      the first effort to study the neurobiology and pharmacology of this PTSD-relevant learning&#xD;
      phenomenon across those with and without PTSD. The objective of this particular proposal is&#xD;
      to apply fMRI and pharmacologic methods to: 1) identify brain mechanisms associated with&#xD;
      generalization of conditioned fear and 2) examine the pharmacologic modifiability of levels&#xD;
      of generalization using a partial agonist at the NMDA receptor complex (D-cycloserine) shown&#xD;
      to increase discrimination of CS+ (danger cue) and CS- (safety cue) in animal studies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To fullfill the objectives of this application, a generalization paradigm has been designed&#xD;
      and psychophysiologically validated in which 6 rings presented on a computer screen gradually&#xD;
      increase in size. For half of participants the smallest ring is the conditioned stimulus&#xD;
      paired with electric shock (CS+) and the largest is the unpaired stimulus (CS-), and for the&#xD;
      other half of participants this is reversed. Activity in fear-related brain structures&#xD;
      measured via fMRI are predicted to gradually decrease as the presented stimulus gradually&#xD;
      becomes less similar to the CS+, forming a generalization slope or gradient. One central&#xD;
      hypothesis of the current application is that DCS (Seromycin) will dose dependently increase&#xD;
      the steepness of generalization gradients (i.e., reduce fear generalization). This study will&#xD;
      include 3 groups of healthy adults recieving either 1) 500 mg Seromycin, 2) 250 mg Seromycin,&#xD;
      or placebo only prior to acquisition of fear conditioning. Twenty four hours later,&#xD;
      participants will return to complete an fMRI during which brain responses to the danger cue&#xD;
      and stimuli resembling the danger cue will be assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">October 1, 2015</completion_date>
  <primary_completion_date type="Actual">October 1, 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>fMRI (BOLD) responses</measure>
    <time_frame>1/1/13-6/1/14</time_frame>
    <description>fMRI (BOLD) responses</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Behavioral assessments of perceived danger</measure>
    <time_frame>up to three years</time_frame>
    <description>Behavioral assessments of perceived danger</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">56</enrollment>
  <condition>Post Traumatic Stress Syndrome</condition>
  <arm_group>
    <arm_group_label>250 mg Seromycin</arm_group_label>
    <description>Healthy adults who will receeve one administration of 250 mg of Seromycin prior to the start of the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>500 mg Seromycin</arm_group_label>
    <description>Healthy adults who will recieve one administration of 500 mg of Seromycin prior to the start of the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <description>Healthy adults who will receive one administration of a placebo pill prior to the start of the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Seromycin</intervention_name>
    <description>250 mg versus 500 mg versus placebo effects on conditioned fear generalization</description>
    <arm_group_label>250 mg Seromycin</arm_group_label>
    <arm_group_label>500 mg Seromycin</arm_group_label>
    <other_name>D-cycloserine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Seromycin</intervention_name>
    <arm_group_label>250 mg Seromycin</arm_group_label>
    <arm_group_label>500 mg Seromycin</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Healthy adults between the ages of 18-55.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy adults between the ages of 18-55.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Current or past Axis I psychiatric diagnosis as determined by self report&#xD;
&#xD;
          2. Current substance dependence or meet criteria for the six month period preceding&#xD;
             testing.&#xD;
&#xD;
          3. Participants will be excluded if they have current or past medical illnesses, which&#xD;
             place the participant at risk or confound the results of the study including:&#xD;
&#xD;
             A) Past history of hypersensitivity to Seromycin B) Current or past epileptic&#xD;
             disorders C) Current depression D) Current anxiety disorders E) Current or past&#xD;
             psychotic disorders F) Current or past renal disease G) Excessive or concurrent use of&#xD;
             alcohol&#xD;
&#xD;
             a) Subjects who are unable to abstain from alcohol for 12 hours prior to testing and 2&#xD;
             days following testing will be excluded&#xD;
&#xD;
          4. Current use of psychoactive medications or medications that alter&#xD;
             central-nervous-system function&#xD;
&#xD;
          5. Females who are pregnant or currently breast-feeding&#xD;
&#xD;
          6. Any metallic implants or objects above the knee, tattoos about the knee, or oral&#xD;
             braces.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 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>University of Minnesota</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>May 2017</verification_date>
  <study_first_submitted>November 19, 2012</study_first_submitted>
  <study_first_submitted_qc>November 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 26, 2012</study_first_posted>
  <last_update_submitted>May 1, 2017</last_update_submitted>
  <last_update_submitted_qc>May 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PTSD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cycloserine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01733030
org study id: MH080130
nct id: NCT01733030
lead sponsor: 
has dmc: No
PROJECT SUMMARY:

      PTSD is a debilitating psychiatric condition precipitated by exposure to extreme, or life
      threatening, trauma with an estimated lifetime prevalence between 8% and 9% in U.S. adults.
      One core symptom of PTSD is intense psychological distress in the presence of stimuli that
      "resemble" one or more aspects of the trauma experience (DSM-IV). This phenomenon referred to
      as stimulus generalization has received surprisingly little empirical testing in the context
      of clinical anxiety in general, and PTSD more specifically. The current proposal represents
      the first effort to study the neurobiology and pharmacology of this PTSD-relevant learning
      phenomenon across those with and without PTSD. The objective of this particular proposal is
      to apply fMRI and pharmacologic methods to: 1) identify brain mechanisms associated with
      generalization of conditioned fear and 2) examine the pharmacologic modifiability of levels
      of generalization using a partial agonist at the NMDA receptor complex (D-cycloserine) shown
      to increase discrimination of CS+ (danger cue) and CS- (safety cue) in animal studies.
To fullfill the objectives of this application, a generalization paradigm has been designed
      and psychophysiologically validated in which 6 rings presented on a computer screen gradually
      increase in size. For half of participants the smallest ring is the conditioned stimulus
      paired with electric shock (CS+) and the largest is the unpaired stimulus (CS-), and for the
      other half of participants this is reversed. Activity in fear-related brain structures
      measured via fMRI are predicted to gradually decrease as the presented stimulus gradually
      becomes less similar to the CS+, forming a generalization slope or gradient. One central
      hypothesis of the current application is that DCS (Seromycin) will dose dependently increase
      the steepness of generalization gradients (i.e., reduce fear generalization). This study will
      include 3 groups of healthy adults recieving either 1) 500 mg Seromycin, 2) 250 mg Seromycin,
      or placebo only prior to acquisition of fear conditioning. Twenty four hours later,
      participants will return to complete an fMRI during which brain responses to the danger cue
      and stimuli resembling the danger cue will be assessed.
observational model: Other
time perspective: Cross-Sectional
measure: fMRI (BOLD) responses
time frame: 1/1/13-6/1/14
description: fMRI (BOLD) responses
measure: Behavioral assessments of perceived danger
time frame: up to three years
description: Behavioral assessments of perceived danger
arm group label: 250 mg Seromycin
description: Healthy adults who will receeve one administration of 250 mg of Seromycin prior to the start of the study.
arm group label: 500 mg Seromycin
description: Healthy adults who will recieve one administration of 500 mg of Seromycin prior to the start of the study.
arm group label: Placebo
description: Healthy adults who will receive one administration of a placebo pill prior to the start of the study.
intervention type: Drug
intervention name: Seromycin
description: 250 mg versus 500 mg versus placebo effects on conditioned fear generalization
arm group label: 250 mg Seromycin
arm group label: 500 mg Seromycin
other name: D-cycloserine
intervention type: Drug
intervention name: Seromycin
arm group label: 250 mg Seromycin
arm group label: 500 mg Seromycin
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Shmuel Lissek, PhD
role: Principal Investigator
affiliation: University of Minnesota
facility: 
country: United States
responsible party type: Sponsor
mesh term: Stress Disorders, Post-Traumatic
mesh term: Cycloserine