<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/NCT03300947</url>
  </required_header>
  <id_info>
    <org_study_id>1707613822</org_study_id>
    <nct_id>NCT03300947</nct_id>
  </id_info>
  <brief_title>Psilocybin for Treatment of Obsessive Compulsive Disorder</brief_title>
  <acronym>PSILOCD</acronym>
  <official_title>Psilocybin for Treatment of Obsessive Compulsive Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Arizona</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Arizona</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate whether psilocybin, a hallucinogenic drug, improves symptoms of&#xD;
      obsessive compulsive disorder (OCD), whether it is safely tolerated as treatment of OCD, and&#xD;
      will investigate the mechanisms by which it works.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study seeks to improve our ability to treat and improve the lives of people who have&#xD;
      obsessive-compulsive disorder (OCD) by exploring the benefits of psilocybin, a mind-altering&#xD;
      drug that changes activity in brain areas believed to be involved in OCD. Anecdotal reports&#xD;
      and results from previous research support this idea. This two-phase study will enroll&#xD;
      patients with symptomatic OCD who are not taking mind-altering medications or street drugs.&#xD;
&#xD;
      During Phase One, neither participants nor the investigators will know which drugs or doses&#xD;
      are administered. This information will be available if it is medically necessary to reveal&#xD;
      which drugs and doses were administered. Five subjects in each group will receive study drug&#xD;
      a total of four times, separated by one week. During Phase Two, participants will not know&#xD;
      which drugs or doses they receive, but the investigators will know. All participants will&#xD;
      receive psilocybin at some point during study participation.&#xD;
&#xD;
      Participants will be randomly assigned to one of the following groups:&#xD;
&#xD;
        1. Low dose (100 µg/kg) psilocybin,&#xD;
&#xD;
        2. High dose (300 µg/kg) psilocybin, or&#xD;
&#xD;
        3. Lorazepam (1 mg), a calming medication. Lorazepam is used often for anxiety and will be&#xD;
           used to mask which drug participants receive.&#xD;
&#xD;
      Participants will spend approximately 12 hours at the research site under observation during&#xD;
      each visit, until they are free of the mind-altering effects of the drug and are determined&#xD;
      by the psychiatrist to be safe to go home accompanied by a responsible adult. The effects of&#xD;
      low versus high doses, and the additive effects of repeated doses will be analyzed and will&#xD;
      be compared to the effects of lorazepam.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 2, 2019</start_date>
  <completion_date type="Anticipated">December 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 30, 2023</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>All participants will be randomly assigned to administration of low dose (100 µg/kg) psilocybin, High dose (300 µg/kg) psilocybin, or Lorazepam (1 mg). Eight different sessions divided in two phases will ensure all subjects are exposed to psilocybin at some point during the study in a blinded fashion.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Phase One: Double blind (both participant AND researchers (In room Care Provider, Investigators, Blinded Outcomes Assessor) Phase Two: Single blind (Participant and Blinded Outcomes Assessor)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Treatment-phase effects on Obsessive-Compulsive symptom severity</measure>
    <time_frame>weekly Y-BOCS rating prior to ingestion of study drug on Week 1 through 8, and week 9 (follow up week 1)</time_frame>
    <description>Prospective Assessment of YBOCS (Yale-Brown Obsessive Compulsive Scale) score comparing each psilocybin dose and active placebo (Lorazepam).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Acute Incidence of Treatment Emergent Adverse Events</measure>
    <time_frame>At 0, and 24 hours after blinded medication ingestion</time_frame>
    <description>Prospective active inquiry of adverse events with the SAFTEE-GI (Systematic Assessment For Treatment Emergent Events-General Inquiry) comparing each psilocybin dose and active placebo (Lorazepam)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Effects on Obsessive-Compulsive symptom severity</measure>
    <time_frame>Follow-up assessments will be conducted weekly over the phone weekly (± 3 days) for one month after last dose, monthly (± 7 days) for three months beginning 28 days after last dose, and then once at 6 months after last dose (± 7 days).</time_frame>
    <description>Prospective Naturalistic Assessment of YBOCS (Yale-Brown Obsessive Compulsive Scale) after repeated administration of study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long Term Incidence and Duration of Treatment Emergent Psychiatric Adverse Events</measure>
    <time_frame>Follow-up assessments will be conducted weekly over the phone (± 3 days) for one month after last dose, monthly (± 7 days) for three months beginning 28 days after last dose, and then once at 6 months after last dose (± 7 days).</time_frame>
    <description>Prospective Assessment with SCID-I (Structured Clinical Interview for DSM-5 Disorders) psychotic screening tool will assess for onset of psychopathology or hallucinogen induced disorders after repeated use.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the magnitude of Error Related Negativity (an electroencephalographic biomarker of OCD) assessed by Error-related negativity (voltage) and mid-frontal theta power (time-frequency approach)</measure>
    <time_frame>Baseline, and 9-10 hours after ingestion of study dose 1, 4, and 8.</time_frame>
    <description>Prospective Assessment of Error Related brain activity comparing each psilocybin dose and active placebo (Lorazepam).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prospective Self-Assessment of Depression Symptoms</measure>
    <time_frame>Baseline, 24 hours after each dose during 8 week active phase, and during the follow-up phase (weekly for one month after last dose, monthly for three months beginning 28 days after last dose, and then once at 6 months after last dose.</time_frame>
    <description>Prospective Assessment of Quick Inventory of Depressive Symptomatology (QIDS) Score comparing each psilocybin dose and active placebo (Lorazepam).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prospective Clinician-Rated Assessment of Depression Symptoms</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks, and during the follow-up phase (weekly for one month after last dose, monthly for three months beginning 28 days after last dose, and then once at 6 months after last dose</time_frame>
    <description>Prospective Assessment of Montgomery-Asberg Depression Rating Scale (MADRS) Score comparing each psilocybin dose and active placebo (Lorazepam).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in functional connectivity: 1) between the Caudate Nucleus (CN) and Orbital Frontal Cortex (OFC); 2) within the default mode network (DMN).</measure>
    <time_frame>Imaging at baseline, and 9-10 hours post ingestion on weeks 1, 4, and 8. YBOCS at baseline and 8 hours after ingestion at weeks 1, 4, and 8.</time_frame>
    <description>Prospective Assessment of Functional Connectivity in CN and OFC and in DMN comparing each psilocybin dose and active placebo (Lorazepam). Also examining whether magnitude of symptom reduction is related to changes in functional connectivity.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Obsessive-compulsive Disorder (OCD)</condition>
  <arm_group>
    <arm_group_label>High-dose Psilocybin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Psilocybin 300 mcg/kg once per week, every week, for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High- or Low-dose Psilocybin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Psilocybin 100 mcg/kg or psilocybin 300 mcg/kg once per week, every week, for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High-dose Psilocybin or Lorazepam</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Psilocybin 300 mcg/kg or Lorazepam 1 mg once per week, every week, for 8 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Psilocybin 100 mcg/kg</intervention_name>
    <description>Psilocybin belongs to the class of hallucinogen or psychedelic drugs. It is one of the major psychoactive components in mushrooms of the Psilocybe genus (&quot;magic mushrooms&quot;).</description>
    <arm_group_label>High- or Low-dose Psilocybin</arm_group_label>
    <other_name>Psilocybine, &quot;magic mushrooms&quot;</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Psilocybin 300 mcg/kg</intervention_name>
    <description>Psilocybin belongs to the class of hallucinogen or psychedelic drugs. It is one of the major psychoactive components in mushrooms of the Psilocybe genus (&quot;magic mushrooms&quot;).</description>
    <arm_group_label>High- or Low-dose Psilocybin</arm_group_label>
    <arm_group_label>High-dose Psilocybin</arm_group_label>
    <arm_group_label>High-dose Psilocybin or Lorazepam</arm_group_label>
    <other_name>Psilocybine, &quot;magic mushrooms&quot;</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lorazepam 1 mg</intervention_name>
    <description>A medication used to treat anxiety belonging to a class of drugs known as benzodiazepines, which act on the central nervous system to produce a calming effect. This drug works by enhancing the effects of a certain natural chemical in the body (GABA).</description>
    <arm_group_label>High-dose Psilocybin or Lorazepam</arm_group_label>
    <other_name>Ativan, Intensol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have moderate to severe OCD (DSM-5) after diagnostic interview using the Structured&#xD;
             Clinical Interview for DSM-5 Research Version (SCID-R).&#xD;
&#xD;
          -  Failed at least one adequate attempted routine care treatment.&#xD;
&#xD;
          -  Considered safe for independent living&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concurrent psychosis, active substance use disorder, or a personal history of&#xD;
             psychosis.&#xD;
&#xD;
          -  Medical illness based on physical examination and routine blood testing that may&#xD;
             complicate cardiovascular safety or drug metabolism or excretion, such as uncontrolled&#xD;
             hypertension, severe cardiac disease, or kidney or liver failure.&#xD;
&#xD;
          -  Unstable Chronic Obstructive Pulmonary Disease (COPD) or severe sleep apnea&#xD;
&#xD;
          -  Psychiatric comorbidity that may represent an acute risk to their own or others'&#xD;
             safety.&#xD;
&#xD;
          -  Subjects may not be using antidepressant medication for OCD for at least two weeks&#xD;
             before receiving study drug, and they cannot require any sedative, narcotic, or&#xD;
             neuroleptic medications on a regular basis. Any of these medications they have taken&#xD;
             should have been stopped long enough in the past to allow for their elimination and&#xD;
             safe withdrawal prior to starting administration of the study drug. The specific time&#xD;
             required will be dependent on the medication the patient was previously receiving.&#xD;
&#xD;
          -  Women who are pregnant, breastfeeding, or unwilling/unable to practice medically&#xD;
             acceptable birth control during the study.&#xD;
&#xD;
          -  Allergy to lorazepam.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francisco A. Moreno, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor of Psychiatry and Associate Vice President, Diversity and Inclusion</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Arizona</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/?term=17196053</url>
    <description>PubMed Abstract Link</description>
  </link>
  <results_reference>
    <citation>Moreno FA, Wiegand CB, Taitano EK, Delgado PL. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J Clin Psychiatry. 2006 Nov;67(11):1735-40. doi: 10.4088/jcp.v67n1110.</citation>
    <PMID>17196053</PMID>
  </results_reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>September 14, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 2017</study_first_posted>
  <last_update_submitted>August 1, 2023</last_update_submitted>
  <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Arizona</investigator_affiliation>
    <investigator_full_name>Francisco A Moreno</investigator_full_name>
    <investigator_title>Associate Vice President, Diversity and Inclusion; Professor, Psychiatry</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Compulsive Personality Disorder</mesh_term>
    <mesh_term>Obsessive-Compulsive Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lorazepam</mesh_term>
    <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/NCT03300947
org study id: 1707613822
nct id: NCT03300947
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate whether psilocybin, a hallucinogenic drug, improves symptoms of
      obsessive compulsive disorder (OCD), whether it is safely tolerated as treatment of OCD, and
      will investigate the mechanisms by which it works.
The study seeks to improve our ability to treat and improve the lives of people who have
      obsessive-compulsive disorder (OCD) by exploring the benefits of psilocybin, a mind-altering
      drug that changes activity in brain areas believed to be involved in OCD. Anecdotal reports
      and results from previous research support this idea. This two-phase study will enroll
      patients with symptomatic OCD who are not taking mind-altering medications or street drugs.

      During Phase One, neither participants nor the investigators will know which drugs or doses
      are administered. This information will be available if it is medically necessary to reveal
      which drugs and doses were administered. Five subjects in each group will receive study drug
      a total of four times, separated by one week. During Phase Two, participants will not know
      which drugs or doses they receive, but the investigators will know. All participants will
      receive psilocybin at some point during study participation.

      Participants will be randomly assigned to one of the following groups:

        1. Low dose (100 µg/kg) psilocybin,

        2. High dose (300 µg/kg) psilocybin, or

        3. Lorazepam (1 mg), a calming medication. Lorazepam is used often for anxiety and will be
           used to mask which drug participants receive.

      Participants will spend approximately 12 hours at the research site under observation during
      each visit, until they are free of the mind-altering effects of the drug and are determined
      by the psychiatrist to be safe to go home accompanied by a responsible adult. The effects of
      low versus high doses, and the additive effects of repeated doses will be analyzed and will
      be compared to the effects of lorazepam.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: All participants will be randomly assigned to administration of low dose (100 µg/kg) psilocybin, High dose (300 µg/kg) psilocybin, or Lorazepam (1 mg). Eight different sessions divided in two phases will ensure all subjects are exposed to psilocybin at some point during the study in a blinded fashion.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Phase One: Double blind (both participant AND researchers (In room Care Provider, Investigators, Blinded Outcomes Assessor) Phase Two: Single blind (Participant and Blinded Outcomes Assessor)
measure: Treatment-phase effects on Obsessive-Compulsive symptom severity
time frame: weekly Y-BOCS rating prior to ingestion of study drug on Week 1 through 8, and week 9 (follow up week 1)
description: Prospective Assessment of YBOCS (Yale-Brown Obsessive Compulsive Scale) score comparing each psilocybin dose and active placebo (Lorazepam).
measure: Acute Incidence of Treatment Emergent Adverse Events
time frame: At 0, and 24 hours after blinded medication ingestion
description: Prospective active inquiry of adverse events with the SAFTEE-GI (Systematic Assessment For Treatment Emergent Events-General Inquiry) comparing each psilocybin dose and active placebo (Lorazepam)
measure: Duration of Effects on Obsessive-Compulsive symptom severity
time frame: Follow-up assessments will be conducted weekly over the phone weekly (± 3 days) for one month after last dose, monthly (± 7 days) for three months beginning 28 days after last dose, and then once at 6 months after last dose (± 7 days).
description: Prospective Naturalistic Assessment of YBOCS (Yale-Brown Obsessive Compulsive Scale) after repeated administration of study drug.
measure: Long Term Incidence and Duration of Treatment Emergent Psychiatric Adverse Events
time frame: Follow-up assessments will be conducted weekly over the phone (± 3 days) for one month after last dose, monthly (± 7 days) for three months beginning 28 days after last dose, and then once at 6 months after last dose (± 7 days).
description: Prospective Assessment with SCID-I (Structured Clinical Interview for DSM-5 Disorders) psychotic screening tool will assess for onset of psychopathology or hallucinogen induced disorders after repeated use.
measure: Changes in the magnitude of Error Related Negativity (an electroencephalographic biomarker of OCD) assessed by Error-related negativity (voltage) and mid-frontal theta power (time-frequency approach)
time frame: Baseline, and 9-10 hours after ingestion of study dose 1, 4, and 8.
description: Prospective Assessment of Error Related brain activity comparing each psilocybin dose and active placebo (Lorazepam).
measure: Prospective Self-Assessment of Depression Symptoms
time frame: Baseline, 24 hours after each dose during 8 week active phase, and during the follow-up phase (weekly for one month after last dose, monthly for three months beginning 28 days after last dose, and then once at 6 months after last dose.
description: Prospective Assessment of Quick Inventory of Depressive Symptomatology (QIDS) Score comparing each psilocybin dose and active placebo (Lorazepam).
measure: Prospective Clinician-Rated Assessment of Depression Symptoms
time frame: Baseline, 4 weeks, 8 weeks, and during the follow-up phase (weekly for one month after last dose, monthly for three months beginning 28 days after last dose, and then once at 6 months after last dose
description: Prospective Assessment of Montgomery-Asberg Depression Rating Scale (MADRS) Score comparing each psilocybin dose and active placebo (Lorazepam).
measure: Changes in functional connectivity: 1) between the Caudate Nucleus (CN) and Orbital Frontal Cortex (OFC); 2) within the default mode network (DMN).
time frame: Imaging at baseline, and 9-10 hours post ingestion on weeks 1, 4, and 8. YBOCS at baseline and 8 hours after ingestion at weeks 1, 4, and 8.
description: Prospective Assessment of Functional Connectivity in CN and OFC and in DMN comparing each psilocybin dose and active placebo (Lorazepam). Also examining whether magnitude of symptom reduction is related to changes in functional connectivity.
arm group label: High-dose Psilocybin
arm group type: Experimental
description: Psilocybin 300 mcg/kg once per week, every week, for 8 weeks
arm group label: High- or Low-dose Psilocybin
arm group type: Experimental
description: Psilocybin 100 mcg/kg or psilocybin 300 mcg/kg once per week, every week, for 8 weeks
arm group label: High-dose Psilocybin or Lorazepam
arm group type: Placebo Comparator
description: Psilocybin 300 mcg/kg or Lorazepam 1 mg once per week, every week, for 8 weeks
intervention type: Drug
intervention name: Psilocybin 100 mcg/kg
description: Psilocybin belongs to the class of hallucinogen or psychedelic drugs. It is one of the major psychoactive components in mushrooms of the Psilocybe genus ("magic mushrooms").
arm group label: High- or Low-dose Psilocybin
other name: Psilocybine, "magic mushrooms"
intervention type: Drug
intervention name: Psilocybin 300 mcg/kg
description: Psilocybin belongs to the class of hallucinogen or psychedelic drugs. It is one of the major psychoactive components in mushrooms of the Psilocybe genus ("magic mushrooms").
arm group label: High- or Low-dose Psilocybin
arm group label: High-dose Psilocybin
arm group label: High-dose Psilocybin or Lorazepam
other name: Psilocybine, "magic mushrooms"
intervention type: Drug
intervention name: Lorazepam 1 mg
description: A medication used to treat anxiety belonging to a class of drugs known as benzodiazepines, which act on the central nervous system to produce a calming effect. This drug works by enhancing the effects of a certain natural chemical in the body (GABA).
arm group label: High-dose Psilocybin or Lorazepam
other name: Ativan, Intensol
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Francisco A. Moreno, MD
role: Principal Investigator
affiliation: Professor of Psychiatry and Associate Vice President, Diversity and Inclusion
facility: 
country: United States
url: https://www.ncbi.nlm.nih.gov/pubmed/?term=17196053
description: PubMed Abstract Link
citation: Moreno FA, Wiegand CB, Taitano EK, Delgado PL. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J Clin Psychiatry. 2006 Nov;67(11):1735-40. doi: 10.4088/jcp.v67n1110.
PMID: 17196053
responsible party type: Principal Investigator
investigator affiliation: University of Arizona
investigator full name: Francisco A Moreno
investigator title: Associate Vice President, Diversity and Inclusion; Professor, Psychiatry
mesh term: Compulsive Personality Disorder
mesh term: Obsessive-Compulsive Disorder
mesh term: Lorazepam
mesh term: Psilocybin
sharing ipd: No