<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/NCT02981173</url>
  </required_header>
  <id_info>
    <org_study_id>1607018057</org_study_id>
    <nct_id>NCT02981173</nct_id>
  </id_info>
  <brief_title>Psilocybin for the Treatment of Cluster Headache</brief_title>
  <official_title>Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Heffter Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ceruvia Lifesciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Yale University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the effects of an oral psilocybin pulse regimen&#xD;
      in cluster headache. Subjects will be randomized to receive oral placebo, low dose&#xD;
      psilocybin, or high dose psilocybin in three experimental sessions, each separated by 5 days.&#xD;
      Subjects will maintain a headache diary prior to, during, and after the pulse regimen in&#xD;
      order to document headache frequency and intensity before, during, and after the pulse&#xD;
      regimen. After at least 6 months from the last experimental session, subjects may be invited&#xD;
      for a second round, in which they will be randomized to receive either low dose or high dose&#xD;
      psilocybin.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Anticipated">September 30, 2023</completion_date>
  <primary_completion_date type="Actual">June 30, 2022</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to first attack after completion of pulse regimen</measure>
    <time_frame>Two months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3)</time_frame>
    <description>Measured in days</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to last attack after completion of pulse regimen</measure>
    <time_frame>Six months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3)</time_frame>
    <description>Measured in days</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in frequency of attacks</measure>
    <time_frame>Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary</time_frame>
    <description>Average number of attacks (number per week)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in intensity of attacks</measure>
    <time_frame>Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary</time_frame>
    <description>Average intensity of attacks (1-10 on visual analog scale)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in duration of attacks</measure>
    <time_frame>Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary</time_frame>
    <description>Average duration of attacks (minutes)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in cluster period duration compared to typical cluster period (episodic subjects only)</measure>
    <time_frame>Measured from 2 weeks before pulse regimen to 6 months following the completion of pulse regimen, then comparing to historical average duration of cluster periods</time_frame>
    <description>Duration of cluster period after intervention (days)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Difference in the change in cluster attack frequency between 1st and 2nd round</measure>
    <time_frame>Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary</time_frame>
    <description>Average number of attacks (number per week); only in those subjects who return for 2nd round</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Difference in the change in cluster attack intensity between 1st and 2nd round</measure>
    <time_frame>Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary</time_frame>
    <description>Average intensity of attacks (1-10 on visual analog scale); only in those subjects who return for 2nd round</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Difference in the change in the duration of attacks between 1st and 2nd round</measure>
    <time_frame>Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary</time_frame>
    <description>Average duration of attacks (minutes); only in those subjects who return for 2nd round</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Use of abortive/rescue medication</measure>
    <time_frame>Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary</time_frame>
    <description>Number of times per week</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Attack-free time</measure>
    <time_frame>Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary</time_frame>
    <description>Number of 24 hour days (may be nonconsecutive)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-Related Quality of life</measure>
    <time_frame>Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary</time_frame>
    <description>Using the CDC's Health-Related Quality of Life (HRQOL) scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Psychedelic effects</measure>
    <time_frame>Taken daily on each experimental day after the resolution of psychedelic effects, approximately 6 hours after drug administration</time_frame>
    <description>Using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in blood pressure</measure>
    <time_frame>Measured during each experimental session prior to drug administration, every 15 min in the first hour after drug administration, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)</time_frame>
    <description>Maximum change from baseline during each experimental session (mmHg)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart rate</measure>
    <time_frame>Measured during each experimental session prior to drug administration, every 15 min in the first hour after drug administration, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)</time_frame>
    <description>Maximum change from baseline during each experimental session (beats per minute)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in peripheral oxygenation</measure>
    <time_frame>Measured during each experimental session prior to drug administration, every 15 min in the first hour after drug administration, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)</time_frame>
    <description>Maximum change from baseline during each experimental session (SpO2)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Cluster Headache</condition>
  <arm_group>
    <arm_group_label>Psilocybin High Dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Psilocybin Low Dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.143 mg/kg Psilocybin or 10 mg Psilocybin</intervention_name>
    <description>0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option) ingested on each of three test days (5 days apart +/- 1-2 days)</description>
    <arm_group_label>Psilocybin High Dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.0143 mg/kg Psilocybin or 1 mg Psilocybin</intervention_name>
    <description>0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin (fixed-dose option) ingested on each of three test days (5 days apart +/- 1-2 days)</description>
    <arm_group_label>Psilocybin Low Dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Microcrystalline cellulose capsule ingested on each of three test days (5 days apart +/- 1-2 days)</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Chronic cluster headache with at least one attack daily&#xD;
&#xD;
          -  Episodic cluster headache with periods that are predictable and have a duration of&#xD;
             approximately 2 months&#xD;
&#xD;
          -  Attacks are managed by means involving no more than twice weekly triptan use (e.g.,&#xD;
             high-flow oxygen, heat/cold pack)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Axis I psychotic disorder (e.g. schizophrenia, bipolar I, depression with psychosis)&#xD;
&#xD;
          -  Axis I psychotic disorder in first degree relative&#xD;
&#xD;
          -  Unstable medical condition, severe renal, cardiac or hepatic disease, pacemaker, or&#xD;
             serious central nervous system pathology&#xD;
&#xD;
          -  Pregnant, breastfeeding, lack of adequate birth control&#xD;
&#xD;
          -  History of intolerance to psilocybin, lysergic acid diethylamide (LSD), or related&#xD;
             compounds&#xD;
&#xD;
          -  Drug or alcohol abuse within the past 3 months (excluding tobacco)&#xD;
&#xD;
          -  Urine toxicology positive to drugs of abuse&#xD;
&#xD;
          -  Use of vasoconstrictive medications (i.e. sumatriptan, pseudoephedrine, midodrine)&#xD;
             within five half-lives of test days&#xD;
&#xD;
          -  Use of serotonergic antiemetics (i.e. ondansetron) in the past 2 weeks&#xD;
&#xD;
          -  Use of antidepressant medications (i.e. amitriptyline, isocarboxazid, fluoxetine,&#xD;
             citalopram) in the past 6 weeks&#xD;
&#xD;
          -  Use of steroids or certain other immunomodulatory agents (i.e. azathioprine) in the&#xD;
             past 2 weeks&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>VA Connecticut Healthcare System</name>
      <address>
        <city>West Haven</city>
        <state>Connecticut</state>
        <zip>06516</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>November 11, 2016</study_first_submitted>
  <study_first_submitted_qc>November 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 5, 2016</study_first_posted>
  <last_update_submitted>June 13, 2023</last_update_submitted>
  <last_update_submitted_qc>June 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Yale University</investigator_affiliation>
    <investigator_full_name>Deepak C. D'Souza</investigator_full_name>
    <investigator_title>Professor of Psychiatry</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cluster Headache</mesh_term>
    <mesh_term>Headache</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psilocybin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT02981173
org study id: 1607018057
nct id: NCT02981173
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to investigate the effects of an oral psilocybin pulse regimen
      in cluster headache. Subjects will be randomized to receive oral placebo, low dose
      psilocybin, or high dose psilocybin in three experimental sessions, each separated by 5 days.
      Subjects will maintain a headache diary prior to, during, and after the pulse regimen in
      order to document headache frequency and intensity before, during, and after the pulse
      regimen. After at least 6 months from the last experimental session, subjects may be invited
      for a second round, in which they will be randomized to receive either low dose or high dose
      psilocybin.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Time to first attack after completion of pulse regimen
time frame: Two months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3)
description: Measured in days
measure: Time to last attack after completion of pulse regimen
time frame: Six months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3)
description: Measured in days
measure: Change in frequency of attacks
time frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
description: Average number of attacks (number per week)
measure: Change in intensity of attacks
time frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
description: Average intensity of attacks (1-10 on visual analog scale)
measure: Change in duration of attacks
time frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
description: Average duration of attacks (minutes)
measure: Change in cluster period duration compared to typical cluster period (episodic subjects only)
time frame: Measured from 2 weeks before pulse regimen to 6 months following the completion of pulse regimen, then comparing to historical average duration of cluster periods
description: Duration of cluster period after intervention (days)
measure: Difference in the change in cluster attack frequency between 1st and 2nd round
time frame: Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary
description: Average number of attacks (number per week); only in those subjects who return for 2nd round
measure: Difference in the change in cluster attack intensity between 1st and 2nd round
time frame: Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary
description: Average intensity of attacks (1-10 on visual analog scale); only in those subjects who return for 2nd round
measure: Difference in the change in the duration of attacks between 1st and 2nd round
time frame: Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary
description: Average duration of attacks (minutes); only in those subjects who return for 2nd round
measure: Use of abortive/rescue medication
time frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
description: Number of times per week
measure: Attack-free time
time frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
description: Number of 24 hour days (may be nonconsecutive)
measure: Health-Related Quality of life
time frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
description: Using the CDC's Health-Related Quality of Life (HRQOL) scale
measure: Psychedelic effects
time frame: Taken daily on each experimental day after the resolution of psychedelic effects, approximately 6 hours after drug administration
description: Using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale
measure: Change in blood pressure
time frame: Measured during each experimental session prior to drug administration, every 15 min in the first hour after drug administration, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
description: Maximum change from baseline during each experimental session (mmHg)
measure: Change in heart rate
time frame: Measured during each experimental session prior to drug administration, every 15 min in the first hour after drug administration, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
description: Maximum change from baseline during each experimental session (beats per minute)
measure: Change in peripheral oxygenation
time frame: Measured during each experimental session prior to drug administration, every 15 min in the first hour after drug administration, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
description: Maximum change from baseline during each experimental session (SpO2)
arm group label: Psilocybin High Dose
arm group type: Active Comparator
arm group label: Psilocybin Low Dose
arm group type: Active Comparator
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: 0.143 mg/kg Psilocybin or 10 mg Psilocybin
description: 0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option) ingested on each of three test days (5 days apart +/- 1-2 days)
arm group label: Psilocybin High Dose
intervention type: Drug
intervention name: 0.0143 mg/kg Psilocybin or 1 mg Psilocybin
description: 0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin (fixed-dose option) ingested on each of three test days (5 days apart +/- 1-2 days)
arm group label: Psilocybin Low Dose
intervention type: Drug
intervention name: Placebo
description: Microcrystalline cellulose capsule ingested on each of three test days (5 days apart +/- 1-2 days)
arm group label: Placebo
criteria: 
gender: All
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Yale University
investigator full name: Deepak C. D'Souza
investigator title: Professor of Psychiatry
mesh term: Cluster Headache
mesh term: Headache
mesh term: Psilocybin
sharing ipd: No