<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/NCT03289949</url>
  </required_header>
  <id_info>
    <org_study_id>H-16026898</org_study_id>
    <nct_id>NCT03289949</nct_id>
  </id_info>
  <brief_title>The Neurobiological Effect of 5-HT2AR Modulation</brief_title>
  <acronym>NeuroPharm2</acronym>
  <official_title>The Neurobiological Effect of 5-HT2AR Modulation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gitte Moos Knudsen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rigshospitalet, Denmark</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 investigators wish to investigate neurobiological effects of serotonin 2A receptor&#xD;
      modulation in healthy volunteers, contrasting effects of an agonist (psilocybin) and an&#xD;
      antagonist (ketanserin). Magnetic resonance imaging (MRI) and positron emission tomography&#xD;
      (PET) will be used as neuroimaging tools.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This project applies an experimental medicine strategy coupled with human functional and&#xD;
      molecular neuroimaging to elucidate the effects of 5-HT2A receptor (5-HT2AR) modulation on&#xD;
      brain function and mood in healthy individuals. We compare psilocybin (5-HT2AR agonist) and&#xD;
      ketanserin (5-HT2AR antagonist) effects on brain function to identify neural mechanisms&#xD;
      mediating the clinical effects of psilocybin and, more broadly, to establish this comparative&#xD;
      strategy as a pathway for delineating pharmacological effects on the brain in humans.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 3, 2017</start_date>
  <completion_date type="Anticipated">June 1, 2027</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2027</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Psilocin/ketanserin blood concentrations and 5-HT2A receptor occupancy (i.e., binding potential).</measure>
    <time_frame>Change in Cimbi-36 binding potential from baseline PET to intervention PET 1 and PET 2 scans (same day for psilocybin, and two consecutive days for ketanserin).</time_frame>
    <description>The investigators aim to model relations psilocin/ketanserin blood drug concentrations and receptor occupancy, using C11-Cimbi-36 PET imaging.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects of psilocybin on Cimbi-36 binding potential at baseline and at one and twelve weeks</measure>
    <time_frame>Change in Cimbi-36 binding potential from baseline to one week post psilocybin (and potentially also at 12 weeks after psilocybin).</time_frame>
    <description>Cimbi-36 PET scan binding potential at baseline and at one-week post psilocybin, and potentially also at 12 weeks post psilocybin.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects of psilocybin and ketanserin on brain function assessed with fMRI and PET</measure>
    <time_frame>Changes in functional connectivity (fMRI) from Baseline MR to intervention MR scans for ketanserin (one or three weeks after baseline MR) and psilocybin (one or three weeks after baseline)</time_frame>
    <description>Correlations between blood levels of ketanserin and psilocin and the estimated associated receptor occupancy with functional MRI neuroimaging data, including resting state networks. Changes in synaptic density will be assessed with 11C-UCB-J PET scans before and 1 week after psilocybin intervention.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects of psilocybin on UCB-J binding potential at baseline and at one week</measure>
    <time_frame>Change in UCB-J binding potential from baseline to one week post psilocybin.</time_frame>
    <description>Project 2, Subproject B. UCB-J PET scan binding potential at baseline and at one-week post psilocybin.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects of psilocybin on brain function assessed with fMRI at baseline and one month</measure>
    <time_frame>Change in fMRI measures from baseline to one month post psilocybin</time_frame>
    <description>Project 2, Subproject C. Resting-state and task-based fMRI measures at baseline and one month post psilocybin.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Basic Science</condition>
  <arm_group>
    <arm_group_label>Project 1: Occupancy of psilocybin/ketanserin</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>After baseline MRI &amp; 5-HT2AR PET-imaging, participants will be allocated to undergo either one oral dose of psilocybine or one oral dose of ketanserin. After drug administration, participants will undergo two CIMBI-36 PET scans.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Project 2: Long term effects of psilocybin</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>After baseline MRI &amp; CIMBI-36 PET-imaging, participants will receive one dose of oral psilocybine intervention. One and 12 weeks after dosing, participants will undergo post-intervention PET-scan.&#xD;
Subproject B: After baseline MRI &amp; UCB-J PET-imaging, participants will receive one dose of oral psilocybine intervention. One week after dosing, participants will undergo post-intervention UCB-J PET-scan.&#xD;
Subproject C: After baseline MR imaging, participants will receive one dose of oral psilocybine (one of two doses: 3mg or ~0.3 mg/kg). One month after dosing, participants will undergo a post-intervention MRI scan.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Project 3: Functional connectivity</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>After baseline MRI scanning and CIMBI-36 PET, participants will undergo one psilocybine-intervention fMRI scan and one ketanserin-intervention fMRI scan. If P2 shows there are long term effects of psilocybine on 5-HT2AR levels, psilocybine will be fixed as the second intervention. If not, interventions will be randomized.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Psilocybine</intervention_name>
    <description>Oral dose of psilocybine.</description>
    <arm_group_label>Project 1: Occupancy of psilocybin/ketanserin</arm_group_label>
    <arm_group_label>Project 2: Long term effects of psilocybin</arm_group_label>
    <arm_group_label>Project 3: Functional connectivity</arm_group_label>
    <other_name>Psilocybin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketanserin</intervention_name>
    <description>Oral dose of ketanserin.</description>
    <arm_group_label>Project 1: Occupancy of psilocybin/ketanserin</arm_group_label>
    <arm_group_label>Project 3: Functional connectivity</arm_group_label>
    <other_name>Ketensin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1) Healthy individuals above 18 years of age.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of or previous primary psychiatric disease (DSM axis 1 or WHO ICD-10&#xD;
             diagnostic classifications) or in first-degree relatives.&#xD;
&#xD;
          2. Previous or present neurological condition/disease, significant somatic&#xD;
             condition/disease or intake of drugs suspected to influence test results.&#xD;
&#xD;
          3. Non-fluent Danish language skills.&#xD;
&#xD;
          4. Vision or hearing impairment.&#xD;
&#xD;
          5. Previous or present learning disability.&#xD;
&#xD;
          6. Pregnancy.&#xD;
&#xD;
          7. Breastfeeding.&#xD;
&#xD;
          8. Contraindications in regard to MRI scanning.&#xD;
&#xD;
          9. Alcohol or drug abuse.&#xD;
&#xD;
         10. Allergy to test drugs.&#xD;
&#xD;
         11. Participation in studies in which participant has received more than 10 mSv of&#xD;
             radiation or other significant exposure to radiation.&#xD;
&#xD;
         12. Abnormal ECG or intake of QT prolonging medication.&#xD;
&#xD;
         13. Previous significant side-effects in regard to hallucinogenic drugs.&#xD;
&#xD;
         14. Use of hallucinogenic drugs 6 months previous to inclusion.&#xD;
&#xD;
         15. Blood donation 3 months before and after project participation&#xD;
&#xD;
         16. Bodyweight under 50 kg.&#xD;
&#xD;
         17. Plasma ferritin levels outside normal range&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gitte M Knudsen, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Neurobiology Research Unit, Rigshospitalet</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gitte M Knudsen, Professor</last_name>
    <phone>+45 35456720</phone>
    <email>gmk@nru.dk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Patrick M Fisher, PhD</last_name>
    <phone>+45 35456714</phone>
    <email>patrick.fisher@nru.dk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Neurobiology Research Unit, Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gitte M Knudsen, Professor</last_name>
    </contact>
    <contact_backup>
      <last_name>Patrick M Fisher, PhD</last_name>
      <phone>+4535456714</phone>
      <email>patrick.fisher@nru.dk</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>September 14, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 21, 2017</study_first_posted>
  <last_update_submitted>August 11, 2022</last_update_submitted>
  <last_update_submitted_qc>August 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Gitte Moos Knudsen</investigator_full_name>
    <investigator_title>Professor, DMsc, MD</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketanserin</mesh_term>
    <mesh_term>Psilocybin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Via database of Center for Integrated Molecular Brain Imaging (Knudsen et al 2016, NeuroImage) data will be available for neuroscience research community contingent on approval by scientific board.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>Upon project completion</ipd_time_frame>
    <ipd_access_criteria>All researchers can request access to data from the database by completing a standardized application form to provide detailed information about the specific database request. The application form and guidelines are available here. Please note that there are some formal requirements that must be fulfilled if the data request is from an international researcher. For example we do not have permission for sharing data outside of the EU, so researchers from a non-EU country will have to come here to work on the data instead.</ipd_access_criteria>
    <ipd_url>https://cimbi.dk/index.php/documents/category/3-cimbi-database</ipd_url>
  </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/NCT03289949
org study id: H-16026898
nct id: NCT03289949
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The investigators wish to investigate neurobiological effects of serotonin 2A receptor
      modulation in healthy volunteers, contrasting effects of an agonist (psilocybin) and an
      antagonist (ketanserin). Magnetic resonance imaging (MRI) and positron emission tomography
      (PET) will be used as neuroimaging tools.
This project applies an experimental medicine strategy coupled with human functional and
      molecular neuroimaging to elucidate the effects of 5-HT2A receptor (5-HT2AR) modulation on
      brain function and mood in healthy individuals. We compare psilocybin (5-HT2AR agonist) and
      ketanserin (5-HT2AR antagonist) effects on brain function to identify neural mechanisms
      mediating the clinical effects of psilocybin and, more broadly, to establish this comparative
      strategy as a pathway for delineating pharmacological effects on the brain in humans.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Basic Science
masking: Single (Participant)
measure: Psilocin/ketanserin blood concentrations and 5-HT2A receptor occupancy (i.e., binding potential).
time frame: Change in Cimbi-36 binding potential from baseline PET to intervention PET 1 and PET 2 scans (same day for psilocybin, and two consecutive days for ketanserin).
description: The investigators aim to model relations psilocin/ketanserin blood drug concentrations and receptor occupancy, using C11-Cimbi-36 PET imaging.
measure: Effects of psilocybin on Cimbi-36 binding potential at baseline and at one and twelve weeks
time frame: Change in Cimbi-36 binding potential from baseline to one week post psilocybin (and potentially also at 12 weeks after psilocybin).
description: Cimbi-36 PET scan binding potential at baseline and at one-week post psilocybin, and potentially also at 12 weeks post psilocybin.
measure: Effects of psilocybin and ketanserin on brain function assessed with fMRI and PET
time frame: Changes in functional connectivity (fMRI) from Baseline MR to intervention MR scans for ketanserin (one or three weeks after baseline MR) and psilocybin (one or three weeks after baseline)
description: Correlations between blood levels of ketanserin and psilocin and the estimated associated receptor occupancy with functional MRI neuroimaging data, including resting state networks. Changes in synaptic density will be assessed with 11C-UCB-J PET scans before and 1 week after psilocybin intervention.
measure: Effects of psilocybin on UCB-J binding potential at baseline and at one week
time frame: Change in UCB-J binding potential from baseline to one week post psilocybin.
description: Project 2, Subproject B. UCB-J PET scan binding potential at baseline and at one-week post psilocybin.
measure: Effects of psilocybin on brain function assessed with fMRI at baseline and one month
time frame: Change in fMRI measures from baseline to one month post psilocybin
description: Project 2, Subproject C. Resting-state and task-based fMRI measures at baseline and one month post psilocybin.
arm group label: Project 1: Occupancy of psilocybin/ketanserin
arm group type: Other
description: After baseline MRI & 5-HT2AR PET-imaging, participants will be allocated to undergo either one oral dose of psilocybine or one oral dose of ketanserin. After drug administration, participants will undergo two CIMBI-36 PET scans.
arm group label: Project 2: Long term effects of psilocybin
arm group type: Other
description: After baseline MRI & CIMBI-36 PET-imaging, participants will receive one dose of oral psilocybine intervention. One and 12 weeks after dosing, participants will undergo post-intervention PET-scan.
Subproject B: After baseline MRI & UCB-J PET-imaging, participants will receive one dose of oral psilocybine intervention. One week after dosing, participants will undergo post-intervention UCB-J PET-scan.
Subproject C: After baseline MR imaging, participants will receive one dose of oral psilocybine (one of two doses: 3mg or ~0.3 mg/kg). One month after dosing, participants will undergo a post-intervention MRI scan.
arm group label: Project 3: Functional connectivity
arm group type: Other
description: After baseline MRI scanning and CIMBI-36 PET, participants will undergo one psilocybine-intervention fMRI scan and one ketanserin-intervention fMRI scan. If P2 shows there are long term effects of psilocybine on 5-HT2AR levels, psilocybine will be fixed as the second intervention. If not, interventions will be randomized.
intervention type: Drug
intervention name: Psilocybine
description: Oral dose of psilocybine.
arm group label: Project 1: Occupancy of psilocybin/ketanserin
arm group label: Project 2: Long term effects of psilocybin
arm group label: Project 3: Functional connectivity
other name: Psilocybin
intervention type: Drug
intervention name: Ketanserin
description: Oral dose of ketanserin.
arm group label: Project 1: Occupancy of psilocybin/ketanserin
arm group label: Project 3: Functional connectivity
other name: Ketensin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Gitte M Knudsen, Professor
role: Study Chair
affiliation: Neurobiology Research Unit, Rigshospitalet
last name: Gitte M Knudsen, Professor
phone: +45 35456720
email: gmk@nru.dk
last name: Patrick M Fisher, PhD
phone: +45 35456714
email: patrick.fisher@nru.dk
facility: 
status: Recruiting
contact: 
contact backup: 
country: Denmark
responsible party type: Sponsor-Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Gitte Moos Knudsen
investigator title: Professor, DMsc, MD
mesh term: Ketanserin
mesh term: Psilocybin
sharing ipd: Yes
ipd description: Via database of Center for Integrated Molecular Brain Imaging (Knudsen et al 2016, NeuroImage) data will be available for neuroscience research community contingent on approval by scientific board.
ipd info type: Study Protocol
ipd time frame: Upon project completion
ipd access criteria: All researchers can request access to data from the database by completing a standardized application form to provide detailed information about the specific database request. The application form and guidelines are available here. Please note that there are some formal requirements that must be fulfilled if the data request is from an international researcher. For example we do not have permission for sharing data outside of the EU, so researchers from a non-EU country will have to come here to work on the data instead.
ipd url: https://cimbi.dk/index.php/documents/category/3-cimbi-database