xml: <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/NCT06017037</url>
    </required_header>
    <id_info>
      <org_study_id>REPAC01</org_study_id>
      <nct_id>NCT06017037</nct_id>
    </id_info>
    <brief_title>REward Processing And Citalopram Study</brief_title>
    <acronym>REPAC</acronym>
    <official_title>REward Processing And Citalopram Study</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this experimental medicine study is to examine the effect of increasing serotonin&#xD;
        on reward processing in healthy volunteers. The main questions it aims to answer are:&#xD;
  &#xD;
          1. Does a subacute increase in serotonin influence the activation regions during reward&#xD;
             learning&#xD;
  &#xD;
          2. Does a subacute increase in serotonin influence behavioural markers of reward valuation&#xD;
             (effort task), responsiveness (taste task) and learning (learning task)&#xD;
  &#xD;
        Participants will be:&#xD;
  &#xD;
        given a 7-day course of the selective serotonin reuptake inhibitor, citalopram. undergo&#xD;
        behavioural testing complete a reward learning task whilst undergoing fMRI&#xD;
  &#xD;
        Researchers will compare results against a placebo group.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">May 19, 2023</start_date>
    <completion_date type="Anticipated">May 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">May 1, 2024</primary_completion_date>
    <phase>Phase 1/Phase 2</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Reward &amp; aversive learning: behavioural correlates</measure>
      <time_frame>Day 7-9 of treatment</time_frame>
      <description>Optimal choice learning rate of conditioned stimuli to win and loss outcomes.&#xD;
  During an instrumental reinforcement learning task participant will complete trials with a pair of symbols (the valence will either be loss or win, which is implicit).&#xD;
  One symbol will be high chance of that outcome (either win or loss depending on the valence of the pair) and the other low chance of the outcome.&#xD;
  In the win pair the optimal choice is the high chance symbol (i.e. to win), in the loss pair the optimal choice is the low chance option (i.e. avoid loss).&#xD;
  In each allocation group the proportion of participants making an optimal choice will be calculated on a trial-by-trial basis. This provide the learning rate outcome.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Reward &amp; aversive learning: neural correlates</measure>
      <time_frame>Day 7-9 of treatment</time_frame>
      <description>Activity of a network of brain regions associated with reward learning (during anticipation and outcome), in response to a positive &amp; negative outcomes in reward learning task.&#xD;
  This will be the difference in BOLD activation in certain brain regions (pertinent to reward processing) between allocation groups during the anticipation stage and the outcome stage of the instrumental learning task.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Resting state</measure>
      <time_frame>Day 7-9 of treatment</time_frame>
      <description>Resting state fMRI activation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Subjective rating of primary reward</measure>
      <time_frame>Day 0 and day 7-9 of treatment</time_frame>
      <description>Subjective rating of four tastes (sweet, salt, sour &amp; bitter) in terms of intensity, anticipation of pleasurableness and actual pleasurableness.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Reward &amp; aversive learning: behavioural volatile reward learning task: total money won</measure>
      <time_frame>day 7-9 of treatment</time_frame>
      <description>Amount of money won/lost &amp; total amount of money received.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Motivational reward task</measure>
      <time_frame>day 7-9 of treatment</time_frame>
      <description>Participants are asked to accept or decline hypothetical offers made of various combinations of reward and physical effort (grip strength). For a limited number of offers participants are asked to actually expend effort for offers too. The investigators will examine&#xD;
  Proportion of offer acceptance for various levels of reward and effort&#xD;
  proportion of accepted offers successfully obtained</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Reward &amp; aversive learning: behavioural volatile reward learning task: learning rate</measure>
      <time_frame>day 7-9 of treatment</time_frame>
      <description>Learning rate of optimal choices changes during the task. Proportion of participants in each allocation arm making an optimal choice on a trial-by-trial basis will provide the learning rate for each group.&#xD;
  Provides sensitive measure of reward and aversive learning rates.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Anhedonia</condition>
    <arm_group>
      <arm_group_label>Citalopram</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Citalopram 20mg p.o. once daily for 7-9 days</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Lactose p.o. once daily for 7-9 days</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Citalopram 20mg</intervention_name>
      <description>Citalopram 20mg tablets, encapsulated to aid blinding. To take per oral once daily for 7-9 days</description>
      <arm_group_label>Citalopram</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Lactose monohydrate tablets encapsulated to aid blinding. To take per oral once daily for 7-9 days</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Participant is willing and able to give informed consent for participation in the&#xD;
               research&#xD;
  &#xD;
            -  Aged between 18 to 65 years&#xD;
  &#xD;
            -  Sufficient knowledge of English language to understand and complete study tasks&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Current or past probable diagnosis of psychiatric illness, according to DSM-5&#xD;
               criteria, requiring intervention by a healthcare professional, including but not&#xD;
               limited to psychosis, bipolar disorder, major depression, OCD, PTSD, substance abuse&#xD;
               disorder or any eating disorder&#xD;
  &#xD;
            -  Current or past diagnosis of any significant personality disorder (e.g. borderline&#xD;
               personality disorder) according to self-report&#xD;
  &#xD;
            -  Diagnosis of attention deficit hyperactive disorder or autistic spectrum disorder that&#xD;
               impairs daily functioning, requires pharmacotherapy or in the opinion of the study&#xD;
               medic would affect the scientific integrity of the study&#xD;
  &#xD;
            -  Current use of medication that might interact with the effects of citalopram or affect&#xD;
               the scientific integrity of the study&#xD;
  &#xD;
            -  Previous suicide attempt or previous prolonged period (e.g. &gt; 5 days) of thoughts to&#xD;
               end life&#xD;
  &#xD;
            -  Known contraindication to citalopram including: past allergic reaction to citalopram&#xD;
               or any other medicines, diagnosis of a cardiovascular condition, glaucoma, type 1 or&#xD;
               type 2 diabetes, diagnosis of epilepsy, previous diagnosis of angle-closure glaucoma,&#xD;
               or current use of any other medication whose use interacts with citalopram (according&#xD;
               to BNF guidance) e.g. associated with prolonged QT-interval&#xD;
  &#xD;
            -  Any other current or past medical conditions which in the opinion of the study medic&#xD;
               may interfere with the safety of the participant or the scientific integrity of the&#xD;
               study including epilepsy/seizures, brain injury, hepatic or renal disease, diabetes,&#xD;
               severe gastro-intestinal problems, Central Nervous System (CNS) tumours, neurological&#xD;
               conditions&#xD;
  &#xD;
            -  First-degree relative with a diagnosis of schizophrenia-spectrum or other psychotic&#xD;
               disorder, or bipolar disorder&#xD;
  &#xD;
            -  Severely underweight (BMI&lt;17) or very obese (BMI&gt;40) in a manner that renders them&#xD;
               unsuitable for the study in the opinion of the study medic&#xD;
  &#xD;
            -  Heavy use of cigarettes (smoke &gt; 20 cigarettes per day)&#xD;
  &#xD;
            -  Heavy use of caffeine (drink &gt; 4 250ml cups/cans of coffee/energy drinks per day)&#xD;
  &#xD;
            -  Lactose intolerance (due to the study involving administration of a lactose placebo&#xD;
               tablet)&#xD;
  &#xD;
            -  Known allergy to citric acid, sodium chloride, sucrose or quinine&#xD;
  &#xD;
            -  Pregnancy (as determined by urine pregnancy test taken during the Part 2 screening&#xD;
               visit), breast feeding or plans to become pregnant&#xD;
  &#xD;
            -  past history of dependence on illicit substances or regular illicit substance use&#xD;
               within previous three months&#xD;
  &#xD;
            -  Evidence of current or past harmful use of alcohol&#xD;
  &#xD;
            -  previous participation in a study involving the tasks used in this study or involving&#xD;
               use of citalopram in the last year&#xD;
  &#xD;
            -  physical (including visual and auditory) or language impairment that would make&#xD;
               complying with the study protocol challenging&#xD;
  &#xD;
            -  ongoing deficit in sense of smell or taste e.g. following Covid-19 infection&#xD;
  &#xD;
            -  Participant is unlikely to comply with the clinical study protocol or is unsuitable&#xD;
               for any other reason, in the opinion of the Investigator&#xD;
  &#xD;
            -  Not suitable for MRI neuroimaging e.g. claustrophobia, difficulty remaining still for&#xD;
               duration of scan&#xD;
  &#xD;
            -  Any MRI contraindications outlined in FMRIB 3 Tesla scanning safety form&#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>Catherine Harmer, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Oxford</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Alexander Smith, MBBS</last_name>
      <phone>07865 618318</phone>
      <email>alexander.smith@psych.ox.ac.uk</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Susannah Murphy, PhD</last_name>
      <email>susannah.murphy@psych.ox.ac.uk</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Neurosciences building, Department of Psychiatry, Warneford hospital</name>
        <address>
          <city>Oxford</city>
          <state>Oxfordshire</state>
          <zip>OX3 7JX</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Alexander Smith</last_name>
        <phone>01865618339</phone>
        <email>Alexander.Smith@psych.ox.ac.uk</email>
      </contact>
      <contact_backup>
        <last_name>Catherine harmer</last_name>
        <email>catherine.harmer@psych.ox.ac.uk</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <verification_date>May 2023</verification_date>
    <study_first_submitted>May 15, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 30, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Anhedonia</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Citalopram</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>Research data will be anonymised and then processed for analysis. Anonymised data will be made available post-publication on Open Science Framework (OSF).&#xD;
  defaced neural images will be shared via governed access through Zenodo with data sharing agreements in place</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06017037
  org study id: REPAC01
  nct id: NCT06017037
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  The goal of this experimental medicine study is to examine the effect of increasing serotonin
        on reward processing in healthy volunteers. The main questions it aims to answer are:
  
          1. Does a subacute increase in serotonin influence the activation regions during reward
             learning
  
          2. Does a subacute increase in serotonin influence behavioural markers of reward valuation
             (effort task), responsiveness (taste task) and learning (learning task)
  
        Participants will be:
  
        given a 7-day course of the selective serotonin reuptake inhibitor, citalopram. undergo
        behavioural testing complete a reward learning task whilst undergoing fMRI
  
        Researchers will compare results against a placebo group.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Reward & aversive learning: behavioural correlates
  time frame: Day 7-9 of treatment
  description: Optimal choice learning rate of conditioned stimuli to win and loss outcomes.
  During an instrumental reinforcement learning task participant will complete trials with a pair of symbols (the valence will either be loss or win, which is implicit).
  One symbol will be high chance of that outcome (either win or loss depending on the valence of the pair) and the other low chance of the outcome.
  In the win pair the optimal choice is the high chance symbol (i.e. to win), in the loss pair the optimal choice is the low chance option (i.e. avoid loss).
  In each allocation group the proportion of participants making an optimal choice will be calculated on a trial-by-trial basis. This provide the learning rate outcome.
  measure: Reward & aversive learning: neural correlates
  time frame: Day 7-9 of treatment
  description: Activity of a network of brain regions associated with reward learning (during anticipation and outcome), in response to a positive & negative outcomes in reward learning task.
  This will be the difference in BOLD activation in certain brain regions (pertinent to reward processing) between allocation groups during the anticipation stage and the outcome stage of the instrumental learning task.
  measure: Resting state
  time frame: Day 7-9 of treatment
  description: Resting state fMRI activation
  measure: Subjective rating of primary reward
  time frame: Day 0 and day 7-9 of treatment
  description: Subjective rating of four tastes (sweet, salt, sour & bitter) in terms of intensity, anticipation of pleasurableness and actual pleasurableness.
  measure: Reward & aversive learning: behavioural volatile reward learning task: total money won
  time frame: day 7-9 of treatment
  description: Amount of money won/lost & total amount of money received.
  measure: Motivational reward task
  time frame: day 7-9 of treatment
  description: Participants are asked to accept or decline hypothetical offers made of various combinations of reward and physical effort (grip strength). For a limited number of offers participants are asked to actually expend effort for offers too. The investigators will examine
  Proportion of offer acceptance for various levels of reward and effort
  proportion of accepted offers successfully obtained
  measure: Reward & aversive learning: behavioural volatile reward learning task: learning rate
  time frame: day 7-9 of treatment
  description: Learning rate of optimal choices changes during the task. Proportion of participants in each allocation arm making an optimal choice on a trial-by-trial basis will provide the learning rate for each group.
  Provides sensitive measure of reward and aversive learning rates.
  arm group label: Citalopram
  arm group type: Experimental
  description: Citalopram 20mg p.o. once daily for 7-9 days
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Lactose p.o. once daily for 7-9 days
  intervention type: Drug
  intervention name: Citalopram 20mg
  description: Citalopram 20mg tablets, encapsulated to aid blinding. To take per oral once daily for 7-9 days
  arm group label: Citalopram
  intervention type: Drug
  intervention name: Placebo
  description: Lactose monohydrate tablets encapsulated to aid blinding. To take per oral once daily for 7-9 days
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Catherine Harmer, PhD
  role: Principal Investigator
  affiliation: University of Oxford
  last name: Alexander Smith, MBBS
  phone: 07865 618318
  email: alexander.smith@psych.ox.ac.uk
  last name: Susannah Murphy, PhD
  email: susannah.murphy@psych.ox.ac.uk
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: United Kingdom
  responsible party type: Sponsor
  mesh term: Anhedonia
  mesh term: Citalopram
  sharing ipd: Undecided
  ipd description: Research data will be anonymised and then processed for analysis. Anonymised data will be made available post-publication on Open Science Framework (OSF).
  defaced neural images will be shared via governed access through Zenodo with data sharing agreements in place