<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/NCT04424420</url>
  </required_header>
  <id_info>
    <org_study_id>2018-004187-60</org_study_id>
    <nct_id>NCT04424420</nct_id>
  </id_info>
  <brief_title>Mental Effects of Analgesic Drugs: Paracetamol and Ibuprofen</brief_title>
  <acronym>MEAD</acronym>
  <official_title>Double Blinded Randomized Placebo Controlled Study on Mental Effects of Analgesic Drugs</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Prof. Jürgen Brockmöller</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Hospital Ulm</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Göttingen</source>
  <oversight_info>
    <has_dmc>Yes</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 objective of the present study is to study paracetamol effects on social pain and empathy&#xD;
      under standardized international conditions (ICH-GCP) for planning, conduction and reporting&#xD;
      of clinical pharmaceutical studies in humans. The study included MRI imaging of brain&#xD;
      activity, analysis of genomic biomarkers potentially explaining interindividual variation. It&#xD;
      is controversial whether the effects are of immediate nature or develop during a period of&#xD;
      about 10 days. Therefore, the study is separated into two study phases. Single dosing (SD) is&#xD;
      applied in study phase 1 and multiple-dosing (MD) in study phase 2. The study compares&#xD;
      paracetamol with placebo and in the study phase 1 also with ibuprofen as analgetically active&#xD;
      control.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 7, 2019</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">March 2021</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>Parallel Assignment</intervention_model>
    <intervention_model_description>Prospective with placebo-controlled</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effect of paracetamol and ibuprofen on social pain and empathy</measure>
    <time_frame>8 hours</time_frame>
    <description>Primary outcome is defined as the composite score of standardized emotional scenarios and the hurt feeling scale.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of paracetamol on social pain and empathy</measure>
    <time_frame>14 days</time_frame>
    <description>Primary outcome is defined as the composite score of standardized emotional scenarios and the hurt feeling scale.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Psychological effects of paracetamol and ibuprofen</measure>
    <time_frame>8 hours</time_frame>
    <description>Interindividual variation of analgesic effects measured using fMRI. MRI will be performed to reflect differences in brain activation by Psychometric test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics effects of paracetamol and ibuprofen</measure>
    <time_frame>8 hours</time_frame>
    <description>Blood samples for determination of study drug concentrations in plasma will be taken at different time-point. This will be used to calculate Maximum Plasma Concentration (Cmax).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacogenes roles in paracetamol and ibuprofen metabolism</measure>
    <time_frame>8 hours</time_frame>
    <description>Genetic analysis of relevant genes responsible for paracetamol and ibuprofen Absorption, Distribution, Metabolism and Excretion (ADME).Healthy volunteers will provide a blood sample for molecular genetic analyses of the various candidate genes, e.g. drug transporters and metabolizing enzymes. This will shed light on the interindividual variation of analgesic effects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Psychological effects of paracetamol</measure>
    <time_frame>14 days</time_frame>
    <description>Interindividual variation of analgesic effects measured using fMRI. MRI will be performed to reflect differences in brain activation by Psychometric test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics effects of paracetamol</measure>
    <time_frame>14 days</time_frame>
    <description>Blood samples for determination of study drug concentrations in plasma will be taken at different time-point. This will be used to calculate Maximum Plasma Concentration (Cmax).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacogenes roles in paracetamol metabolism</measure>
    <time_frame>14 days</time_frame>
    <description>Genetic analysis of relevant genes responsible for paracetamol Absorption, Distribution, Metabolism and Excretion (ADME). Healthy volunteers will provide a blood sample for molecular genetic analyses of the various candidate genes, e.g. drug transporters and metabolizing enzymes. This will shed light on the interindividual variation of analgesic effects.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Empathy</condition>
  <arm_group>
    <arm_group_label>Paracetamol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study phase 1 (single dosing): 1000 mg once. Study phase 2 (multiple dosing): 1000 mg twice daily for a minimum of 12 and a maximum of 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ibuprofen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Study phase 1 (single dosing): 800 mg once.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Study phase 1 (single dosing): Once. Study phase 2 (multiple dosing): Twice daily for a minimum of 12 and a maximum of 14 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paracetamol</intervention_name>
    <description>Paracetamol oral tablet</description>
    <arm_group_label>Paracetamol</arm_group_label>
    <other_name>Acetaminophen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibuprofen</intervention_name>
    <description>Ibuprofen oral tablet</description>
    <arm_group_label>Ibuprofen</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral tablet</intervention_name>
    <description>Sugar pill manufactured to mimic the Paracetamol and Ibuprofen.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent obtained prior to study.&#xD;
&#xD;
          2. Willingness to meet the study instructions and to co-operate with the study personal.&#xD;
&#xD;
          3. No clinically relevant pathological findings in any of the investigations at the&#xD;
             screening visit; minor deviations of laboratory values from the normal range may be&#xD;
             accepted if judged by the investigator to have no clinical relevance.&#xD;
&#xD;
          4. Body weight not less than 48 kg and body mass index (BMI) not less than 17 kg/m² and&#xD;
             not greater than 32 kg/m².&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pacemaker devices, implantable or external ones.&#xD;
&#xD;
          2. Involvement in the planning and conduct of the study (applies to staff directly&#xD;
             employed at the study site / department).&#xD;
&#xD;
          3. Known pregnancy or lactation period.&#xD;
&#xD;
          4. History of alcohol and / or drug abuse and / or any abusive use of medicaments.&#xD;
&#xD;
          5. Any disease affecting liver or kidney or impairment of the liver or kidney-function.&#xD;
&#xD;
          6. History of severe hypersensitivity reactions, anaphylaxis, psychiatric or neurologic&#xD;
             disorder.&#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>
  <overall_contact>
    <last_name>Jürgen Brockmöller, Prof.</last_name>
    <phone>+49 (0) 551 39-53 11</phone>
    <email>jbrockm@gwdg.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Johannes Matthaei, Dr.med.</last_name>
    <email>matthaei.j@googlemail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Universitätsmedizin Göttingen</name>
      <address>
        <city>Göttingen</city>
        <state>Niedersachsen</state>
        <zip>37075</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jürgen Brockmöller, Prof.</last_name>
      <phone>+49(0)551 39 5311</phone>
      <email>jbrockm@gwdg.de</email>
    </contact>
    <contact_backup>
      <last_name>Alexandra Sachkova</last_name>
      <phone>+4917627786662</phone>
      <email>alexandra.sachkova@med.uni-goettingen.de</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>February 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>June 5, 2020</last_update_submitted>
  <last_update_submitted_qc>June 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Göttingen</investigator_affiliation>
    <investigator_full_name>Prof. Jürgen Brockmöller</investigator_full_name>
    <investigator_title>Director, Institute of Clinical Pharmacology at Universitätsmedizin Göttingen</investigator_title>
  </responsible_party>
  <keyword>Mental effects</keyword>
  <keyword>Social Pain</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</mesh_term>
    <mesh_term>Ibuprofen</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/NCT04424420
org study id: 2018-004187-60
nct id: NCT04424420
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The objective of the present study is to study paracetamol effects on social pain and empathy
      under standardized international conditions (ICH-GCP) for planning, conduction and reporting
      of clinical pharmaceutical studies in humans. The study included MRI imaging of brain
      activity, analysis of genomic biomarkers potentially explaining interindividual variation. It
      is controversial whether the effects are of immediate nature or develop during a period of
      about 10 days. Therefore, the study is separated into two study phases. Single dosing (SD) is
      applied in study phase 1 and multiple-dosing (MD) in study phase 2. The study compares
      paracetamol with placebo and in the study phase 1 also with ibuprofen as analgetically active
      control.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective with placebo-controlled
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Effect of paracetamol and ibuprofen on social pain and empathy
time frame: 8 hours
description: Primary outcome is defined as the composite score of standardized emotional scenarios and the hurt feeling scale.
measure: Effect of paracetamol on social pain and empathy
time frame: 14 days
description: Primary outcome is defined as the composite score of standardized emotional scenarios and the hurt feeling scale.
measure: Psychological effects of paracetamol and ibuprofen
time frame: 8 hours
description: Interindividual variation of analgesic effects measured using fMRI. MRI will be performed to reflect differences in brain activation by Psychometric test.
measure: Pharmacokinetics effects of paracetamol and ibuprofen
time frame: 8 hours
description: Blood samples for determination of study drug concentrations in plasma will be taken at different time-point. This will be used to calculate Maximum Plasma Concentration (Cmax).
measure: Pharmacogenes roles in paracetamol and ibuprofen metabolism
time frame: 8 hours
description: Genetic analysis of relevant genes responsible for paracetamol and ibuprofen Absorption, Distribution, Metabolism and Excretion (ADME).Healthy volunteers will provide a blood sample for molecular genetic analyses of the various candidate genes, e.g. drug transporters and metabolizing enzymes. This will shed light on the interindividual variation of analgesic effects.
measure: Psychological effects of paracetamol
time frame: 14 days
description: Interindividual variation of analgesic effects measured using fMRI. MRI will be performed to reflect differences in brain activation by Psychometric test.
measure: Pharmacokinetics effects of paracetamol
time frame: 14 days
description: Blood samples for determination of study drug concentrations in plasma will be taken at different time-point. This will be used to calculate Maximum Plasma Concentration (Cmax).
measure: Pharmacogenes roles in paracetamol metabolism
time frame: 14 days
description: Genetic analysis of relevant genes responsible for paracetamol Absorption, Distribution, Metabolism and Excretion (ADME). Healthy volunteers will provide a blood sample for molecular genetic analyses of the various candidate genes, e.g. drug transporters and metabolizing enzymes. This will shed light on the interindividual variation of analgesic effects.
arm group label: Paracetamol
arm group type: Experimental
description: Study phase 1 (single dosing): 1000 mg once. Study phase 2 (multiple dosing): 1000 mg twice daily for a minimum of 12 and a maximum of 14 days.
arm group label: Ibuprofen
arm group type: Active Comparator
description: Study phase 1 (single dosing): 800 mg once.
arm group label: Placebo
arm group type: Placebo Comparator
description: Study phase 1 (single dosing): Once. Study phase 2 (multiple dosing): Twice daily for a minimum of 12 and a maximum of 14 days.
intervention type: Drug
intervention name: Paracetamol
description: Paracetamol oral tablet
arm group label: Paracetamol
other name: Acetaminophen
intervention type: Drug
intervention name: Ibuprofen
description: Ibuprofen oral tablet
arm group label: Ibuprofen
intervention type: Drug
intervention name: Placebo oral tablet
description: Sugar pill manufactured to mimic the Paracetamol and Ibuprofen.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jürgen Brockmöller, Prof.
phone: +49 (0) 551 39-53 11
email: jbrockm@gwdg.de
last name: Johannes Matthaei, Dr.med.
email: matthaei.j@googlemail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Germany
responsible party type: Sponsor-Investigator
investigator affiliation: University of Göttingen
investigator full name: Prof. Jürgen Brockmöller
investigator title: Director, Institute of Clinical Pharmacology at Universitätsmedizin Göttingen
mesh term: Acetaminophen
mesh term: Ibuprofen