<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/NCT03754062</url>
  </required_header>
  <id_info>
    <org_study_id>HR-16/17-0603</org_study_id>
    <nct_id>NCT03754062</nct_id>
  </id_info>
  <brief_title>Pharmacological Modulation of Belief Salience</brief_title>
  <acronym>MOBS</acronym>
  <official_title>Pharmacological Modulation of Belief Salience</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>King's College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medical Research Council</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>King's College London</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>
      To provide an initial test of the hypothesis that dopamine mediates the motivational salience&#xD;
      of stimuli beyond simple stimulus-reinforcement associations, the researchers propose to&#xD;
      undertake a study of the modulation of a) levels of agreement or disagreement with; b) the&#xD;
      perceived self- relevance; and c) the perceived interest of propositions expressing beliefs&#xD;
      and values in healthy male volunteers using Ii) a dopamine antagonist (the D2-blocker&#xD;
      haloperidol), and (ii) a dopamine precursor L-Dopa to increase CNS dopamine transmission.&#xD;
&#xD;
      The researchers will also administer the Salience Attribution Task (SAT) which will allow&#xD;
      researchers to assess reward-learning processing of simple stimuli using a reaction-time&#xD;
      game. This task was utilised by Roiser et al in order to explore whether delusions in&#xD;
      medicated patients with schizophrenia were related to impairments in associative learning.&#xD;
      The authors hypothesised that associative learning was influenced by D2 receptor blockade.&#xD;
      The researchers extend this approach to examine the effect of dopamine modulation on the SAT&#xD;
      as a measure of associative learning, a basic neuropsychological process that may be involved&#xD;
      in the attribution of salience to beliefs.&#xD;
&#xD;
      Finally, the researchers will ask participants to perform a within-subjects dictator game to&#xD;
      understand the influence of dopaminergic manipulation of the live attribution of harm&#xD;
      intention to partners. The task has been previously validated online. Participants will play&#xD;
      against 3 partners in a random order in each drug condition. Each partner will play the&#xD;
      participant for 6 trials. One partner will always be fair, one will always be unfair, and one&#xD;
      will be 50% unfair. We aim to understand whether potentiating dopamine has an additive effect&#xD;
      on the harm intention attributions toward partners, regardless of the behaviour of the&#xD;
      partner.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Delusions in psychiatry are viewed as a form of aberrant belief. Consequently it is important&#xD;
      to understand the cognitive and neural processes involved in beliefs to provide insights into&#xD;
      how these processes go awry in the formation of delusions. Beliefs have been defined as 'a&#xD;
      disposition to express, assent to, or otherwise act in accordance with some proposition'.&#xD;
      Some beliefs are widely held within a given society (e.g the earth revolves around the sun;&#xD;
      eating humans is wrong), whereas others vary in association with subcultural and individual&#xD;
      differences (e.g God created the universe; abortion is wrong). Similarly, the conviction or&#xD;
      agreement with which an individual's beliefs and values are held may change over time, to the&#xD;
      extent that some beliefs and values may be lost, and others acquired. Also, the perceived&#xD;
      relevance of beliefs and values to oneself may vary. For example, beliefs that the 'earth&#xD;
      revolves around the sun' and that 'global warming is occurring' may both be held with&#xD;
      conviction, but the latter may be perceived as having higher relevance to the self in terms&#xD;
      of risk, and potential life-style changes. Hence, self-relevance is a dimension of beliefs&#xD;
      that is potentially dissociable from the conviction (level of agreement) with which a belief&#xD;
      is held. Further, some propositions expressing beliefs and values may be regarded as more&#xD;
      interesting than others. This raises the question of what neurobiological processes&#xD;
      contribute to the sense of conviction for, and perceived self-relevance and interest of&#xD;
      beliefs and values?&#xD;
&#xD;
      The mesolimbic dopamine system is a candidate neural system implicated in mediating the&#xD;
      motivational salience of perceptions and ideas, 'whereby events and thoughts come to grab&#xD;
      attention, drive action, and influence goal-directed behaviour because of their association&#xD;
      with reward or punishment'. In human studies, haloperidol has been used to show that dopamine&#xD;
      activity influences action-value estimates represented in the striatum during instrumental&#xD;
      conditioning, as would be expected from earlier studies of feedback-based learning. Still&#xD;
      other data suggest that brain regions rich in dopaminergic inputs play a role in processing&#xD;
      the salience of rewarding events. What is not known is if these dopaminergic rich regions&#xD;
      also modulate the motivational salience of more complex 'stimuli' including ideas and&#xD;
      beliefs.&#xD;
&#xD;
      Main hypothesis:&#xD;
&#xD;
      Prediction 1:&#xD;
&#xD;
      At a neurobiological level, the hypothesis is that the mesolimbic dopamine system is&#xD;
      recruited to tag representations (ideas and beliefs) as motivationally salient. Potentiation&#xD;
      of dopamine transmission should increase salience of beliefs (as indicated by increases in&#xD;
      agreement, self-relevance and interest toward propositions within science, paranormal,&#xD;
      politics, moral, and religious themes in the Beliefs and Values Inventory while attenuation&#xD;
      of dopamine transmission should be associated with decreased salience. Answers of items&#xD;
      within themes will be summed to create summary scores that will be split by agreement,&#xD;
      interest, and self-relevance dimensions.&#xD;
&#xD;
      Prediction 2:&#xD;
&#xD;
      Potentiating dopamine be associated with increased attribution of harmful intent to partners&#xD;
      across all trials (but trait paranoia will not be associated with variation in attributions&#xD;
      of self-interest) of a within-subjects dictator game.&#xD;
&#xD;
      Prediction 3:&#xD;
&#xD;
      Attribution of harmful intent to different dictators will follow a dose-response relationship&#xD;
      (fair &lt; partially fair &lt; unfair) across all ranges of dopamine potentiation. However, L-Dopa&#xD;
      conditions will have a higher baseline of average harmful intent. There will be no&#xD;
      interaction between dopamine manipulations and dictator fairness on attribution of harmful&#xD;
      intent.&#xD;
&#xD;
      If these hypotheses receive empirical support, it would be relevant to understanding the role&#xD;
      of the dopamine system in normal cognitive processes involved in expressing or acting in&#xD;
      accordance with beliefs. It would also be relevant to determining the role of dopamine&#xD;
      dysregulation in psychosis (in delusion formation). Also, reduced levels of the&#xD;
      meaningfulness of experience following antipsychotic administration (as indexed by reduced&#xD;
      agreement for and perceived self- relevance and interest of beliefs and values) would&#xD;
      identify a potential reason for non-compliance with antipsychotic treatment.&#xD;
&#xD;
      Supplementary hypotheses:&#xD;
&#xD;
      There will be an interaction between condition (placebo, dopamine blockade, dopamine&#xD;
      potentiation) x dimension (agreement, self-relevance, interest), whereby self-relevance and&#xD;
      interest are affected more by dopamine modulation than agreement. This might explain why&#xD;
      patients with delusions who are given antipsychotics will continue to say that they believe&#xD;
      'x,' but don't think about it as much, and cease to act upon it.&#xD;
&#xD;
      Aims:&#xD;
&#xD;
      To provide an initial test of the hypothesis that dopamine mediates the motivational salience&#xD;
      of stimuli beyond simple stimulus-reinforcement associations, we propose to undertake a study&#xD;
      of the modulation of a) levels of agreement or disagreement with; b) the perceived self-&#xD;
      relevance; and c) the perceived interest of propositions expressing beliefs and values in&#xD;
      healthy male volunteers using i) a dopamine antagonist (the D2-blocker haloperidol), and (ii)&#xD;
      a dopamine precursor L-Dopa to increase CNS dopamine transmission.&#xD;
&#xD;
      The researchers will also administer the Salience Attribution Task (SAT) which will allow the&#xD;
      researchers to assess reward-learning processing of simple stimuli using a reaction-time&#xD;
      game. This task was utilised by Roiser et al. in order to explore whether delusions in&#xD;
      medicated patients with schizophrenia were related to impairments in associative learning.&#xD;
      The authors hypothesised that associative learning was influenced by D2 receptor blockade. We&#xD;
      extend this approach to examine the effect of dopamine modulation on the SAT as a measure of&#xD;
      associative learning, a basic neuropsychological process that may be involved in the&#xD;
      attribution of salience to beliefs.&#xD;
&#xD;
      Finally, the researchers will ask participants to perform a within-subjects dictator game to&#xD;
      understand the influence of dopaminergic manipulation of the. Participants will play against&#xD;
      3 partners in a random order in each drug condition. Each partner will play the participant&#xD;
      for 6 trials. One partner will always be fair, one will always be unfair, and one will be 50%&#xD;
      unfair. We aim to understand whether potentiating dopamine has an additive effect on the harm&#xD;
      intention attributions toward partners, regardless of the behaviour of the partner.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2017</start_date>
  <completion_date type="Actual">September 1, 2019</completion_date>
  <primary_completion_date type="Actual">September 1, 2019</primary_completion_date>
  <phase>Phase 1</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>
    <intervention_model_description>Placebo x Haloperidol x LDOPA</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>Beliefs and Values Inventory (BVI)</measure>
    <time_frame>12 Months</time_frame>
    <description>Change in score between conditions on the BVI. Scores will be summed by item totals within theme (paranormal, religion, morality, politics, and science) and dimension (agreement, self-relevance, and interest).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Salience Attribution Test (SAT)</measure>
    <time_frame>12 Months</time_frame>
    <description>Change in attribution of explicit and implicit salience between conditions on the SAT.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Within-subjects dictator game</measure>
    <time_frame>12 Months</time_frame>
    <description>Participants will play against three different partners, each for six trials. In each trial, the player's partner will have the option to either split or take 10p from the player, so that the player either ends up with 5p or 0p. Players will play against one partner that will always split the money, one that will always take all of the money, and one that will 50% of the time split the money. After each trial, the player will be asked on a scale of 1-100 (1 being not at all and 100 being completely):&#xD;
How much do you think your partner was driven by a desire to increase their own bonus, and&#xD;
How much do you think your partner was driven by a desire to reduce your bonus.&#xD;
Total of a. and b. will be added up for each style of partner for each arm.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Big-5 Personality Questionnaire</measure>
    <time_frame>6 Months</time_frame>
    <description>The researchers will calculate the associations between personality dimensions of the Big-5 (extraversion, neuroticism, openness, agreeableness, and conscientiousness) using the 25 item version (scores from 1-5 on a likert scale, with 5 meaning higher agreement with a statement) with variation within-subjects.&#xD;
Each dimension will be totalled to calculate personality variation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brief Oxford-Liverpool Inventory of Experiences and Feelings</measure>
    <time_frame>6 Months</time_frame>
    <description>The researchers will calculate the associations between baseline schizotypy scores with variation within-subjects across conditions.&#xD;
Unusual Experiences (hallucinations etc), Cognitive Disorganisation (cognitive difficulties), Introvertive Anhedonia (loss of pleasure etc.), and Impulsive Nonconformity (impulsiveness) sub-scales will be added up individually (from a scale of 1-5 for each item, 5 being higher agreement with an item) to calculate schizotypy on a number of dimensions.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Haloperidol</condition>
  <condition>Placebo</condition>
  <condition>L-DOPA</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo control</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Haloperidol 3mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Haloperidol</description>
  </arm_group>
  <arm_group>
    <arm_group_label>L-Dopa 150 mg &amp; Domperidone 10mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>L-Dopa</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo - Cap</intervention_name>
    <description>Administration of Placebo by pill.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>L-dopa</intervention_name>
    <description>Administration of L-dopa by pill.</description>
    <arm_group_label>L-Dopa 150 mg &amp; Domperidone 10mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Haloperidol</intervention_name>
    <description>Administration of Haloperidol by pill.</description>
    <arm_group_label>Haloperidol 3mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males between the ages of 18-65&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History or current psychiatric or neurological illness, history or current serious&#xD;
             medical diagnosis, BMI outside of normal/healthy range, smoker over 5 cigarettes per&#xD;
             day, recent use of drugs, non-english speaker.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Male</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Centre for Neuroimaging Sciences</name>
      <address>
        <city>London</city>
        <zip>W1T 7NF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <results_reference>
    <citation>Schmidt K, Roiser JP. Assessing the construct validity of aberrant salience. Front Behav Neurosci. 2009 Dec 23;3:58. doi: 10.3389/neuro.08.058.2009. eCollection 2009.</citation>
    <PMID>20057930</PMID>
  </results_reference>
  <results_reference>
    <citation>Kapur S. Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am J Psychiatry. 2003 Jan;160(1):13-23. doi: 10.1176/appi.ajp.160.1.13.</citation>
    <PMID>12505794</PMID>
  </results_reference>
  <results_reference>
    <citation>Pessiglione M, Seymour B, Flandin G, Dolan RJ, Frith CD. Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans. Nature. 2006 Aug 31;442(7106):1042-5. doi: 10.1038/nature05051. Epub 2006 Aug 23.</citation>
    <PMID>16929307</PMID>
  </results_reference>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>October 23, 2018</study_first_submitted>
  <study_first_submitted_qc>November 22, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>October 9, 2019</last_update_submitted>
  <last_update_submitted_qc>October 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 10, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Haloperidol</mesh_term>
    <mesh_term>Haloperidol decanoate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Share anonymised data after collection on the Open Science Framework.</ipd_description>
  </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/NCT03754062
org study id: HR-16/17-0603
nct id: NCT03754062
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
To provide an initial test of the hypothesis that dopamine mediates the motivational salience
      of stimuli beyond simple stimulus-reinforcement associations, the researchers propose to
      undertake a study of the modulation of a) levels of agreement or disagreement with; b) the
      perceived self- relevance; and c) the perceived interest of propositions expressing beliefs
      and values in healthy male volunteers using Ii) a dopamine antagonist (the D2-blocker
      haloperidol), and (ii) a dopamine precursor L-Dopa to increase CNS dopamine transmission.

      The researchers will also administer the Salience Attribution Task (SAT) which will allow
      researchers to assess reward-learning processing of simple stimuli using a reaction-time
      game. This task was utilised by Roiser et al in order to explore whether delusions in
      medicated patients with schizophrenia were related to impairments in associative learning.
      The authors hypothesised that associative learning was influenced by D2 receptor blockade.
      The researchers extend this approach to examine the effect of dopamine modulation on the SAT
      as a measure of associative learning, a basic neuropsychological process that may be involved
      in the attribution of salience to beliefs.

      Finally, the researchers will ask participants to perform a within-subjects dictator game to
      understand the influence of dopaminergic manipulation of the live attribution of harm
      intention to partners. The task has been previously validated online. Participants will play
      against 3 partners in a random order in each drug condition. Each partner will play the
      participant for 6 trials. One partner will always be fair, one will always be unfair, and one
      will be 50% unfair. We aim to understand whether potentiating dopamine has an additive effect
      on the harm intention attributions toward partners, regardless of the behaviour of the
      partner.
Delusions in psychiatry are viewed as a form of aberrant belief. Consequently it is important
      to understand the cognitive and neural processes involved in beliefs to provide insights into
      how these processes go awry in the formation of delusions. Beliefs have been defined as 'a
      disposition to express, assent to, or otherwise act in accordance with some proposition'.
      Some beliefs are widely held within a given society (e.g the earth revolves around the sun;
      eating humans is wrong), whereas others vary in association with subcultural and individual
      differences (e.g God created the universe; abortion is wrong). Similarly, the conviction or
      agreement with which an individual's beliefs and values are held may change over time, to the
      extent that some beliefs and values may be lost, and others acquired. Also, the perceived
      relevance of beliefs and values to oneself may vary. For example, beliefs that the 'earth
      revolves around the sun' and that 'global warming is occurring' may both be held with
      conviction, but the latter may be perceived as having higher relevance to the self in terms
      of risk, and potential life-style changes. Hence, self-relevance is a dimension of beliefs
      that is potentially dissociable from the conviction (level of agreement) with which a belief
      is held. Further, some propositions expressing beliefs and values may be regarded as more
      interesting than others. This raises the question of what neurobiological processes
      contribute to the sense of conviction for, and perceived self-relevance and interest of
      beliefs and values?

      The mesolimbic dopamine system is a candidate neural system implicated in mediating the
      motivational salience of perceptions and ideas, 'whereby events and thoughts come to grab
      attention, drive action, and influence goal-directed behaviour because of their association
      with reward or punishment'. In human studies, haloperidol has been used to show that dopamine
      activity influences action-value estimates represented in the striatum during instrumental
      conditioning, as would be expected from earlier studies of feedback-based learning. Still
      other data suggest that brain regions rich in dopaminergic inputs play a role in processing
      the salience of rewarding events. What is not known is if these dopaminergic rich regions
      also modulate the motivational salience of more complex 'stimuli' including ideas and
      beliefs.

      Main hypothesis:

      Prediction 1:

      At a neurobiological level, the hypothesis is that the mesolimbic dopamine system is
      recruited to tag representations (ideas and beliefs) as motivationally salient. Potentiation
      of dopamine transmission should increase salience of beliefs (as indicated by increases in
      agreement, self-relevance and interest toward propositions within science, paranormal,
      politics, moral, and religious themes in the Beliefs and Values Inventory while attenuation
      of dopamine transmission should be associated with decreased salience. Answers of items
      within themes will be summed to create summary scores that will be split by agreement,
      interest, and self-relevance dimensions.

      Prediction 2:

      Potentiating dopamine be associated with increased attribution of harmful intent to partners
      across all trials (but trait paranoia will not be associated with variation in attributions
      of self-interest) of a within-subjects dictator game.

      Prediction 3:

      Attribution of harmful intent to different dictators will follow a dose-response relationship
      (fair < partially fair < unfair) across all ranges of dopamine potentiation. However, L-Dopa
      conditions will have a higher baseline of average harmful intent. There will be no
      interaction between dopamine manipulations and dictator fairness on attribution of harmful
      intent.

      If these hypotheses receive empirical support, it would be relevant to understanding the role
      of the dopamine system in normal cognitive processes involved in expressing or acting in
      accordance with beliefs. It would also be relevant to determining the role of dopamine
      dysregulation in psychosis (in delusion formation). Also, reduced levels of the
      meaningfulness of experience following antipsychotic administration (as indexed by reduced
      agreement for and perceived self- relevance and interest of beliefs and values) would
      identify a potential reason for non-compliance with antipsychotic treatment.

      Supplementary hypotheses:

      There will be an interaction between condition (placebo, dopamine blockade, dopamine
      potentiation) x dimension (agreement, self-relevance, interest), whereby self-relevance and
      interest are affected more by dopamine modulation than agreement. This might explain why
      patients with delusions who are given antipsychotics will continue to say that they believe
      'x,' but don't think about it as much, and cease to act upon it.

      Aims:

      To provide an initial test of the hypothesis that dopamine mediates the motivational salience
      of stimuli beyond simple stimulus-reinforcement associations, we propose to undertake a study
      of the modulation of a) levels of agreement or disagreement with; b) the perceived self-
      relevance; and c) the perceived interest of propositions expressing beliefs and values in
      healthy male volunteers using i) a dopamine antagonist (the D2-blocker haloperidol), and (ii)
      a dopamine precursor L-Dopa to increase CNS dopamine transmission.

      The researchers will also administer the Salience Attribution Task (SAT) which will allow the
      researchers to assess reward-learning processing of simple stimuli using a reaction-time
      game. This task was utilised by Roiser et al. in order to explore whether delusions in
      medicated patients with schizophrenia were related to impairments in associative learning.
      The authors hypothesised that associative learning was influenced by D2 receptor blockade. We
      extend this approach to examine the effect of dopamine modulation on the SAT as a measure of
      associative learning, a basic neuropsychological process that may be involved in the
      attribution of salience to beliefs.

      Finally, the researchers will ask participants to perform a within-subjects dictator game to
      understand the influence of dopaminergic manipulation of the. Participants will play against
      3 partners in a random order in each drug condition. Each partner will play the participant
      for 6 trials. One partner will always be fair, one will always be unfair, and one will be 50%
      unfair. We aim to understand whether potentiating dopamine has an additive effect on the harm
      intention attributions toward partners, regardless of the behaviour of the partner.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Placebo x Haloperidol x LDOPA
primary purpose: Basic Science
masking: Double (Participant, Investigator)
masking description: Double blind
measure: Beliefs and Values Inventory (BVI)
time frame: 12 Months
description: Change in score between conditions on the BVI. Scores will be summed by item totals within theme (paranormal, religion, morality, politics, and science) and dimension (agreement, self-relevance, and interest).
measure: Salience Attribution Test (SAT)
time frame: 12 Months
description: Change in attribution of explicit and implicit salience between conditions on the SAT.
measure: Within-subjects dictator game
time frame: 12 Months
description: Participants will play against three different partners, each for six trials. In each trial, the player's partner will have the option to either split or take 10p from the player, so that the player either ends up with 5p or 0p. Players will play against one partner that will always split the money, one that will always take all of the money, and one that will 50% of the time split the money. After each trial, the player will be asked on a scale of 1-100 (1 being not at all and 100 being completely):
How much do you think your partner was driven by a desire to increase their own bonus, and
How much do you think your partner was driven by a desire to reduce your bonus.
Total of a. and b. will be added up for each style of partner for each arm.
measure: Big-5 Personality Questionnaire
time frame: 6 Months
description: The researchers will calculate the associations between personality dimensions of the Big-5 (extraversion, neuroticism, openness, agreeableness, and conscientiousness) using the 25 item version (scores from 1-5 on a likert scale, with 5 meaning higher agreement with a statement) with variation within-subjects.
Each dimension will be totalled to calculate personality variation.
measure: Brief Oxford-Liverpool Inventory of Experiences and Feelings
time frame: 6 Months
description: The researchers will calculate the associations between baseline schizotypy scores with variation within-subjects across conditions.
Unusual Experiences (hallucinations etc), Cognitive Disorganisation (cognitive difficulties), Introvertive Anhedonia (loss of pleasure etc.), and Impulsive Nonconformity (impulsiveness) sub-scales will be added up individually (from a scale of 1-5 for each item, 5 being higher agreement with an item) to calculate schizotypy on a number of dimensions.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo control
arm group label: Haloperidol 3mg
arm group type: Experimental
description: Haloperidol
arm group label: L-Dopa 150 mg & Domperidone 10mg
arm group type: Experimental
description: L-Dopa
intervention type: Drug
intervention name: Placebo - Cap
description: Administration of Placebo by pill.
arm group label: Placebo
intervention type: Drug
intervention name: L-dopa
description: Administration of L-dopa by pill.
arm group label: L-Dopa 150 mg & Domperidone 10mg
intervention type: Drug
intervention name: Haloperidol
description: Administration of Haloperidol by pill.
arm group label: Haloperidol 3mg
criteria: 
gender: Male
gender based: Yes
gender description: Male
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Kingdom
citation: Schmidt K, Roiser JP. Assessing the construct validity of aberrant salience. Front Behav Neurosci. 2009 Dec 23;3:58. doi: 10.3389/neuro.08.058.2009. eCollection 2009.
PMID: 20057930
citation: Kapur S. Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am J Psychiatry. 2003 Jan;160(1):13-23. doi: 10.1176/appi.ajp.160.1.13.
PMID: 12505794
citation: Pessiglione M, Seymour B, Flandin G, Dolan RJ, Frith CD. Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans. Nature. 2006 Aug 31;442(7106):1042-5. doi: 10.1038/nature05051. Epub 2006 Aug 23.
PMID: 16929307
responsible party type: Sponsor
mesh term: Haloperidol
mesh term: Haloperidol decanoate
sharing ipd: Yes
ipd description: Share anonymised data after collection on the Open Science Framework.