<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/NCT02235012</url>
  </required_header>
  <id_info>
    <org_study_id>D512</org_study_id>
    <secondary_id>2013-002056-33</secondary_id>
    <nct_id>NCT02235012</nct_id>
  </id_info>
  <brief_title>Cognitive Biases Under Ketamine</brief_title>
  <acronym>KETABI</acronym>
  <official_title>Cognitive Biases in Decision Making in a Pharmacological Model of Psychosis : a Study in Healthy Humans Recieving Low Dose Anesthetic, Ketamine Versus Placebo</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier St Anne</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fondation pour la Recherche Médicale</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fondation Fyssen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Comité pour la Recherche Hospitalière Médicale</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Association Schizo Oui</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre Hospitalier St Anne</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Characterise cognitive biases resulting from low dose ketamine infusion, used as a&#xD;
      pharmacological model of psychosis.&#xD;
&#xD;
      Our assumption is that low dose ketamine results in reasoning biases by impairing the way&#xD;
      uncertainty is monitored and taken into account for decision making.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ketamine is a non-competitive glutamate NMDA antagonist. The infusion of subanesthetic doses&#xD;
      of ketamine results in sub-clinical schizophrenia-like positive symptoms in healthy controls.&#xD;
      The safety of ketamine use is attested by its daily use in child anesthesia and by a number&#xD;
      of studies showing there is no medical, neural or cognitive complication after a single&#xD;
      infusion.&#xD;
&#xD;
      Low dose ketamine is therefore a valid and safe human model to study psychosis. The objective&#xD;
      of the study is to characterise cognitive biases resulting from low dose ketamine infusion,&#xD;
      used as a pharmacological model of psychosis.&#xD;
&#xD;
      We designed four distinct paradigms designed to better characterize these biases.&#xD;
&#xD;
      P1 is a neuroeconomic task where subjects have to make binary choices to maximize gains, in a&#xD;
      situation where either direct feedback information or additional counterfactual information&#xD;
      is provided.&#xD;
&#xD;
      P2 is a neuroeconomic task where a direct manipulation of uncertainty is performed, and its&#xD;
      impact on decision is measured.&#xD;
&#xD;
      P3 is a perceptual decision making task, where subjects have to classify a gabor orientation&#xD;
      into the diagonal or cardinal category based on a rapidly presented series of individual&#xD;
      gabors. The contribution of each piece of evidence to the final decision is measured and&#xD;
      correlated to fluctuations in eeg data.&#xD;
&#xD;
      P4 is a perceptual decision making task, where subjects have to determine the global&#xD;
      orientation of a series of sequentially presented gabor stimulus. There are interim responses&#xD;
      and final responses, the influence of the former on the latter (confirmation bias) is&#xD;
      studied.&#xD;
&#xD;
      Our assumption is that low dose ketamine results in reasoning biases by impairing the way&#xD;
      uncertainty is monitored and taken into account for decision making.&#xD;
&#xD;
      The study design is as follows : randomized, double blind, controlled, against placebo,&#xD;
      cross-over.&#xD;
&#xD;
      Healthy subjects will therefore be randomized to receive on the first visit either a ketamine&#xD;
      infusion or a placebo infusion. The alternative condition will be applied on the second&#xD;
      visit.&#xD;
&#xD;
      Ketamine will be prepared using KETAMINE PANPHARMA 250 mg/5mL, and infusion will be. This&#xD;
      procedure should produce ketamine plasmatic levels of 140ng/ml. Two blood samples will be&#xD;
      taken 30 and 90 minutes after infusion start to record actual ketamine plasmatic levels.&#xD;
&#xD;
      Placebo infusion will follow the same pattern of infusion, prepared using CHLORURE DE SODIUM&#xD;
      0,9% MACOPHARMA.&#xD;
&#xD;
      We will record both behavioral, electrophysiologic and psychometric data. Detailed&#xD;
      assumptions are as folllows :&#xD;
&#xD;
      Behavioral data :&#xD;
&#xD;
      P1 and 2 : Significant impairment with ketamine in the ability to take into account&#xD;
      uncertainty to guide decisions.&#xD;
&#xD;
      P3 : Significant decrease with ketamine in the ability to classify correctly the mean spatial&#xD;
      orientation of stimuli according to the cardinal or diagonal direction.&#xD;
&#xD;
      P4 : Significant increase with ketamine in the confirmation bias following the interim&#xD;
      choice.&#xD;
&#xD;
      Electroencephalographic data :&#xD;
&#xD;
      Correlation between the impairment in the ability to take into account uncertainty and the&#xD;
      alteration of the Error Related Negativity and late inhibitory eeg signals, and decreased&#xD;
      long distance synchrony as indicated by spectral analysis (P1 and 2).&#xD;
&#xD;
      The covariation of brain activity with the weight each stimuli sample will have in the final&#xD;
      decision, will be increased as a result of ketamine infusion (P3).&#xD;
&#xD;
      Psychometric data :&#xD;
&#xD;
      Increase in the Brief Psychiatric Rating Scale (BPRS) as a result of ketamine infusion. The&#xD;
      BPRS scale records the psychotic symtoms and is translated and validated in a french&#xD;
      population sample.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 8, 2014</start_date>
  <completion_date type="Anticipated">October 2019</completion_date>
  <primary_completion_date type="Anticipated">October 2019</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>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evidence for biaises in decision making in an uncertain environment.</measure>
    <time_frame>During infusion of Ketamine / Placebo (expected 2 hours)</time_frame>
    <description>Behavioural analyses of decision making during the neuroeconomic or perceptual decision makin tasks (Paradigms 1 to 4)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Electroencephalographic data</measure>
    <time_frame>During infusion of Ketamine / Placebo (expected 2 hours)</time_frame>
    <description>Correlation between the impairment in the ability to take into account uncertainty and the alteration of the Error Related Negativity and late inhibitory eeg signals, and decreased long distance synchrony as indicated by spectral analysis (Paradigms 1 and 2).&#xD;
The covariation of brain activity with the weight each stimuli sample will have in the final decision, will be increased as a result of ketamine infusion (Paradigm 3)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brief Psychiatric Rating Scale (BPRS)</measure>
    <time_frame>30 and 90 minutes after infusion onset</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate</measure>
    <time_frame>Every 15 minutes during infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulse oxymetry</measure>
    <time_frame>Every 15 minutes during infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>Every 15 minutes during infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinician administred dissociatives states scales (CADSS)</measure>
    <time_frame>30 and 90 minutes after infusion onset</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">48</enrollment>
  <condition>Healthy Subjects</condition>
  <arm_group>
    <arm_group_label>Ketamine then placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Infusion of low dose Ketamine then infusion of a saline solution</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo then ketamin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Infusion of a saline solution then infusion of low dose Ketamine</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>KETAMINE PANPHARMA 250 mg/5mL, solution for infusion :&#xD;
Initial rapid infusion of 0,23 mg/kg&#xD;
Infusion from minute 2 to minute 30 : 0,00967 mg/kg/min&#xD;
Infusion from minute 31 to minute 120 : 0,00483 mg/kg/min</description>
    <arm_group_label>Ketamine then placebo</arm_group_label>
    <arm_group_label>Placebo then ketamin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>CHLORURE DE SODIUM 0,9 % MACOPHARMA :&#xD;
Initial rapid infusion of 0,23 mg/kg&#xD;
Infusion from minute 2 to minute 30 : 0,00967 mg/kg/min&#xD;
Infusion from minute 31 to minute 120 : 0,00483 mg/kg/min</description>
    <arm_group_label>Ketamine then placebo</arm_group_label>
    <arm_group_label>Placebo then ketamin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Right-handed (as assessed by the Edinburgh scale)&#xD;
&#xD;
          -  Aged 18 to 39&#xD;
&#xD;
          -  Having given an informed consent&#xD;
&#xD;
          -  Health insurance&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breastfeeding woman (a urine pregnancy test will be offered in doubt)&#xD;
&#xD;
          -  Personal or first-degree family history of psychosis&#xD;
&#xD;
          -  Personal history of mood disorder, anxiety disorder, obsessive-compulsive disorder,&#xD;
             somatoform disorder, dependence on a psychoactive substance, behavior disorder&#xD;
             incompatible with a 2 hours EEG recording.&#xD;
&#xD;
          -  Psychotropic treatment, current or stopped for less than 1 month, including&#xD;
             antidepressant, anxiolytic but excluding hypnotic treatments.&#xD;
&#xD;
          -  Personal history of neurologic disorder in relation to the central nervous system :&#xD;
             congenital malformation of the brain, brain tumor, multiple sclerosis, degenerative&#xD;
             disease of the central nervous system, epilepsy, current or in remission for less than&#xD;
             3 years or still requiring a medical treatment, inflammatory disease of the central&#xD;
             nervous system dating under a year or having resulted in sequelae.&#xD;
&#xD;
          -  Known hypertension or blood pressure above 140/90 mmHg upon clinical examination,&#xD;
             congenital heart disease, ischemic heart disease, cardiac insufficiency,&#xD;
             supraventricular and ventricular heart rhythm disorder.&#xD;
&#xD;
          -  Person with restricted liberty, as a result of judicial or administrative measures&#xD;
&#xD;
          -  Persons under involuntary commitment as a result of a psychiatric disorder.&#xD;
&#xD;
          -  Person subject to a measure of legal protection or unable to consent.&#xD;
&#xD;
          -  Known intolerance ketamine.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>39 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Raphaël GAILLARD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Hospitalier St Anne</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Raphaël GODARD, MD, PhD</last_name>
    <phone>00 33 1 45 65 81 54</phone>
    <email>r.gaillard@ch-sainte-anne.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Marie GODARD</last_name>
    <phone>00 33 1 45 65 77 28</phone>
    <email>m.godard@ch-sainte-anne.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Centre Hospitalier Sainte Anne</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Raphaël GAILLARD, MD, PhD</last_name>
      <phone>00 33 1 45 65 81 54</phone>
      <email>r.gaillard@ch-sainte-anne.fr</email>
    </contact>
    <contact_backup>
      <last_name>Marie GODARD</last_name>
      <phone>00 33 1 45 65 77 28</phone>
      <email>m.godard@ch-sainte-anne.fr</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>August 12, 2014</study_first_submitted>
  <study_first_submitted_qc>September 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 9, 2014</study_first_posted>
  <last_update_submitted>October 18, 2017</last_update_submitted>
  <last_update_submitted_qc>October 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Schizophrenia</keyword>
  <keyword>Ketamine</keyword>
  <keyword>Cognitive biases</keyword>
  <keyword>Uncertainty</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</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/NCT02235012
org study id: D512
secondary id: 2013-002056-33
nct id: NCT02235012
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Characterise cognitive biases resulting from low dose ketamine infusion, used as a
      pharmacological model of psychosis.

      Our assumption is that low dose ketamine results in reasoning biases by impairing the way
      uncertainty is monitored and taken into account for decision making.
Ketamine is a non-competitive glutamate NMDA antagonist. The infusion of subanesthetic doses
      of ketamine results in sub-clinical schizophrenia-like positive symptoms in healthy controls.
      The safety of ketamine use is attested by its daily use in child anesthesia and by a number
      of studies showing there is no medical, neural or cognitive complication after a single
      infusion.

      Low dose ketamine is therefore a valid and safe human model to study psychosis. The objective
      of the study is to characterise cognitive biases resulting from low dose ketamine infusion,
      used as a pharmacological model of psychosis.

      We designed four distinct paradigms designed to better characterize these biases.

      P1 is a neuroeconomic task where subjects have to make binary choices to maximize gains, in a
      situation where either direct feedback information or additional counterfactual information
      is provided.

      P2 is a neuroeconomic task where a direct manipulation of uncertainty is performed, and its
      impact on decision is measured.

      P3 is a perceptual decision making task, where subjects have to classify a gabor orientation
      into the diagonal or cardinal category based on a rapidly presented series of individual
      gabors. The contribution of each piece of evidence to the final decision is measured and
      correlated to fluctuations in eeg data.

      P4 is a perceptual decision making task, where subjects have to determine the global
      orientation of a series of sequentially presented gabor stimulus. There are interim responses
      and final responses, the influence of the former on the latter (confirmation bias) is
      studied.

      Our assumption is that low dose ketamine results in reasoning biases by impairing the way
      uncertainty is monitored and taken into account for decision making.

      The study design is as follows : randomized, double blind, controlled, against placebo,
      cross-over.

      Healthy subjects will therefore be randomized to receive on the first visit either a ketamine
      infusion or a placebo infusion. The alternative condition will be applied on the second
      visit.

      Ketamine will be prepared using KETAMINE PANPHARMA 250 mg/5mL, and infusion will be. This
      procedure should produce ketamine plasmatic levels of 140ng/ml. Two blood samples will be
      taken 30 and 90 minutes after infusion start to record actual ketamine plasmatic levels.

      Placebo infusion will follow the same pattern of infusion, prepared using CHLORURE DE SODIUM
      0,9% MACOPHARMA.

      We will record both behavioral, electrophysiologic and psychometric data. Detailed
      assumptions are as folllows :

      Behavioral data :

      P1 and 2 : Significant impairment with ketamine in the ability to take into account
      uncertainty to guide decisions.

      P3 : Significant decrease with ketamine in the ability to classify correctly the mean spatial
      orientation of stimuli according to the cardinal or diagonal direction.

      P4 : Significant increase with ketamine in the confirmation bias following the interim
      choice.

      Electroencephalographic data :

      Correlation between the impairment in the ability to take into account uncertainty and the
      alteration of the Error Related Negativity and late inhibitory eeg signals, and decreased
      long distance synchrony as indicated by spectral analysis (P1 and 2).

      The covariation of brain activity with the weight each stimuli sample will have in the final
      decision, will be increased as a result of ketamine infusion (P3).

      Psychometric data :

      Increase in the Brief Psychiatric Rating Scale (BPRS) as a result of ketamine infusion. The
      BPRS scale records the psychotic symtoms and is translated and validated in a french
      population sample.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Triple (Participant, Care Provider, Investigator)
measure: Evidence for biaises in decision making in an uncertain environment.
time frame: During infusion of Ketamine / Placebo (expected 2 hours)
description: Behavioural analyses of decision making during the neuroeconomic or perceptual decision makin tasks (Paradigms 1 to 4)
measure: Electroencephalographic data
time frame: During infusion of Ketamine / Placebo (expected 2 hours)
description: Correlation between the impairment in the ability to take into account uncertainty and the alteration of the Error Related Negativity and late inhibitory eeg signals, and decreased long distance synchrony as indicated by spectral analysis (Paradigms 1 and 2).
The covariation of brain activity with the weight each stimuli sample will have in the final decision, will be increased as a result of ketamine infusion (Paradigm 3)
measure: Brief Psychiatric Rating Scale (BPRS)
time frame: 30 and 90 minutes after infusion onset
measure: Heart rate
time frame: Every 15 minutes during infusion
measure: Pulse oxymetry
time frame: Every 15 minutes during infusion
measure: Blood pressure
time frame: Every 15 minutes during infusion
measure: Clinician administred dissociatives states scales (CADSS)
time frame: 30 and 90 minutes after infusion onset
arm group label: Ketamine then placebo
arm group type: Experimental
description: Infusion of low dose Ketamine then infusion of a saline solution
arm group label: Placebo then ketamin
arm group type: Experimental
description: Infusion of a saline solution then infusion of low dose Ketamine
intervention type: Drug
intervention name: Ketamine
description: KETAMINE PANPHARMA 250 mg/5mL, solution for infusion :
Initial rapid infusion of 0,23 mg/kg
Infusion from minute 2 to minute 30 : 0,00967 mg/kg/min
Infusion from minute 31 to minute 120 : 0,00483 mg/kg/min
arm group label: Ketamine then placebo
arm group label: Placebo then ketamin
intervention type: Drug
intervention name: Placebo
description: CHLORURE DE SODIUM 0,9 % MACOPHARMA :
Initial rapid infusion of 0,23 mg/kg
Infusion from minute 2 to minute 30 : 0,00967 mg/kg/min
Infusion from minute 31 to minute 120 : 0,00483 mg/kg/min
arm group label: Ketamine then placebo
arm group label: Placebo then ketamin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 39 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Raphaël GAILLARD
role: Principal Investigator
affiliation: Centre Hospitalier St Anne
last name: Raphaël GODARD, MD, PhD
phone: 00 33 1 45 65 81 54
email: r.gaillard@ch-sainte-anne.fr
last name: Marie GODARD
phone: 00 33 1 45 65 77 28
email: m.godard@ch-sainte-anne.fr
facility: 
status: Recruiting
contact: 
contact backup: 
country: France
responsible party type: Sponsor
mesh term: Ketamine