<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/NCT03763409</url>
  </required_header>
  <id_info>
    <org_study_id>R56384/RE001</org_study_id>
    <nct_id>NCT03763409</nct_id>
  </id_info>
  <brief_title>Losartan and Emotional Memory</brief_title>
  <official_title>The Effect of Losartan on Emotional Memory in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Oxford</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>
      This study explores the effects of single-dose losartan (50mg) versus identical placebo&#xD;
      capsule on emotional memory and learning in healthy volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The commonly prescribed antihypertensive drug losartan (brand name: Cozaar; UK licensed for&#xD;
      20 years) targets the renin-angiotensin system - a hormone system regulating blood pressure -&#xD;
      by acting as an angiotensin receptor antagonist. In particular, the drug prevents a docking&#xD;
      of the protein angiotensin IV to AT1 receptors, which leads to a dilation if vessels and a&#xD;
      reduction in blood pressure. However, the increase in free angiotensin IV has also been&#xD;
      associated with an increase in synaptic plasticity, the cellular mechanism involved in&#xD;
      learning and memory. As such, losartan appears to have cognition-enhancing properties, in a&#xD;
      way that a single dose of 50mg improves prospective memory in healthy humans. However,&#xD;
      preliminary pre-clinical results also suggest that a single injection of the drug improves&#xD;
      fear extinction in rodents, which is the equivalent to human cognitive-behavioural therapy&#xD;
      for anxiety disorders. Furthermore, compared to other antihypertensive drugs, regular&#xD;
      losartan treatment appears to prevent the development of post-traumatic stress disorder&#xD;
      symptoms following trauma exposition. Such results suggest that the renin-angiotensin system&#xD;
      plays a key role in the development and extinction of anxiety, and that adding losartan to&#xD;
      cognitive-behavioural therapy for anxiety in humans might have synergistic effects. However,&#xD;
      it remains to be clarified what the basic effects of this drug on emotional information&#xD;
      processing in humans are to identify mechanisms by which it may improve psychological&#xD;
      treatments.&#xD;
&#xD;
      In this study, the key neuropsychological effects of probing the renin-angiotensin system on&#xD;
      emotional information processing and learning will be investigated. In a double-blind,&#xD;
      randomised between-groups design, 54 healthy volunteers will be randomised to a group&#xD;
      receiving a single dose of losartan (50mg) versus placebo. When peak plasma levels are&#xD;
      reached, participants will work on a battery of behavioural measures of emotional information&#xD;
      processing and learning.&#xD;
&#xD;
      The results from this study will help understand how the renin-angiotensin system affects&#xD;
      emotional information processing and learning, and they will help establish a battery of&#xD;
      tasks that sensitively respond to such manipulations. Such information will ultimately lead&#xD;
      to the development of losartan and similar agents for the more effective and more compact&#xD;
      treatment of anxiety disorders.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2018</start_date>
  <completion_date type="Actual">September 28, 2018</completion_date>
  <primary_completion_date type="Actual">September 28, 2018</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>Parallel Assignment</intervention_model>
    <intervention_model_description>Parallel randomised</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>double-blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>aversive and appetitive learning</measure>
    <time_frame>1 hour after capsule intake</time_frame>
    <description>a learning task wil assess to what degree participants learn from win versus loss outcomes in different environments</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">53</enrollment>
  <condition>Memory</condition>
  <condition>Learning</condition>
  <arm_group>
    <arm_group_label>losartan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50 mg single-dose oral losartan</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>microcellulose placebo in identical capsule</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Losartan Potassium</intervention_name>
    <description>active drug</description>
    <arm_group_label>losartan</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>placebo</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  willing and able to provide informed consent&#xD;
&#xD;
          -  male or Female, aged 18-50&#xD;
&#xD;
          -  body mass index (BMI) of 18-30 kg/m2&#xD;
&#xD;
          -  fluent English skills&#xD;
&#xD;
          -  non- or light-smoker (&lt; 5 cigarettes a day)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female participant who is pregnant or breast-feeding&#xD;
&#xD;
          -  CNS-active medication during the last 6 weeks&#xD;
&#xD;
          -  Current blood pressure or other heart medication (especially aliskiren or beta&#xD;
             blockers)&#xD;
&#xD;
          -  Intravascular fluid depletion&#xD;
&#xD;
          -  Past or present DSM-IV axis-I diagnosis or suspected diagnosis (from SCID results at&#xD;
             screening)&#xD;
&#xD;
          -  Alcohol or substance abuse&#xD;
&#xD;
          -  First-degree family member with a history of a severe psychiatric disease&#xD;
&#xD;
          -  Impaired liver or kidney function&#xD;
&#xD;
          -  Lifetime history of epilepsy or other neurological disease, systemic infection, or&#xD;
             clinically significant hepatic, cardiac, obstructive respiratory, renal,&#xD;
             cerebrovascular, metabolic, endocrine or pulmonary disease or disorder which, in the&#xD;
             opinion of the investigator, may either put the participants at risk because of&#xD;
             participation in the study, or may influence the result of the study, or the&#xD;
             participant's ability to participate in the study.&#xD;
&#xD;
          -  Insufficient English skills&#xD;
&#xD;
          -  participated in another study involving CNS-active medication during the last 6 weeks&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Department of Psychiatry, University of Oxford</name>
      <address>
        <city>Oxford</city>
        <zip>OX37JX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>December 3, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>December 4, 2018</last_update_submitted>
  <last_update_submitted_qc>December 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>anxiety</keyword>
  <keyword>losartan</keyword>
  <keyword>appetitive learning</keyword>
  <keyword>aversive learning</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Losartan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03763409
org study id: R56384/RE001
nct id: NCT03763409
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study explores the effects of single-dose losartan (50mg) versus identical placebo
      capsule on emotional memory and learning in healthy volunteers.
The commonly prescribed antihypertensive drug losartan (brand name: Cozaar; UK licensed for
      20 years) targets the renin-angiotensin system - a hormone system regulating blood pressure -
      by acting as an angiotensin receptor antagonist. In particular, the drug prevents a docking
      of the protein angiotensin IV to AT1 receptors, which leads to a dilation if vessels and a
      reduction in blood pressure. However, the increase in free angiotensin IV has also been
      associated with an increase in synaptic plasticity, the cellular mechanism involved in
      learning and memory. As such, losartan appears to have cognition-enhancing properties, in a
      way that a single dose of 50mg improves prospective memory in healthy humans. However,
      preliminary pre-clinical results also suggest that a single injection of the drug improves
      fear extinction in rodents, which is the equivalent to human cognitive-behavioural therapy
      for anxiety disorders. Furthermore, compared to other antihypertensive drugs, regular
      losartan treatment appears to prevent the development of post-traumatic stress disorder
      symptoms following trauma exposition. Such results suggest that the renin-angiotensin system
      plays a key role in the development and extinction of anxiety, and that adding losartan to
      cognitive-behavioural therapy for anxiety in humans might have synergistic effects. However,
      it remains to be clarified what the basic effects of this drug on emotional information
      processing in humans are to identify mechanisms by which it may improve psychological
      treatments.

      In this study, the key neuropsychological effects of probing the renin-angiotensin system on
      emotional information processing and learning will be investigated. In a double-blind,
      randomised between-groups design, 54 healthy volunteers will be randomised to a group
      receiving a single dose of losartan (50mg) versus placebo. When peak plasma levels are
      reached, participants will work on a battery of behavioural measures of emotional information
      processing and learning.

      The results from this study will help understand how the renin-angiotensin system affects
      emotional information processing and learning, and they will help establish a battery of
      tasks that sensitively respond to such manipulations. Such information will ultimately lead
      to the development of losartan and similar agents for the more effective and more compact
      treatment of anxiety disorders.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Parallel randomised
primary purpose: Basic Science
masking: Double (Participant, Investigator)
masking description: double-blind
measure: aversive and appetitive learning
time frame: 1 hour after capsule intake
description: a learning task wil assess to what degree participants learn from win versus loss outcomes in different environments
arm group label: losartan
arm group type: Experimental
description: 50 mg single-dose oral losartan
arm group label: placebo
arm group type: Placebo Comparator
description: microcellulose placebo in identical capsule
intervention type: Drug
intervention name: Losartan Potassium
description: active drug
arm group label: losartan
intervention type: Other
intervention name: placebo
description: placebo
arm group label: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Losartan
sharing ipd: Undecided