<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/NCT03282123</url>
  </required_header>
  <id_info>
    <org_study_id>MP-16</org_study_id>
    <nct_id>NCT03282123</nct_id>
  </id_info>
  <brief_title>Open Label Multi-Site Study of Safety and Effects of MDMA-assisted Therapy for Treatment of PTSD</brief_title>
  <official_title>An Open-Label, Multi-Site Phase 2 Study of the Safety and Effect of Manualized MDMA-Assisted Therapy for the Treatment of Severe Posttraumatic Stress Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Multidisciplinary Association for Psychedelic Studies</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Multidisciplinary Association for Psychedelic Studies</source>
  <oversight_info>
    <has_dmc>No</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 multi-site, open-label, Phase 2, lead-in study assesses the safety and effect of&#xD;
      3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy in participants diagnosed with at&#xD;
      least severe posttraumatic stress disorder (PTSD). Therapy teams that have been identified&#xD;
      and trained to work on the sponsor's planned Phase 3 studies will treat at least one&#xD;
      open-label participant in this study.&#xD;
&#xD;
      This study will compare the effects of three open-label manualized Experimental Sessions of&#xD;
      therapy assisted by flexible doses of MDMA. Initial doses per Experimental Session include 80&#xD;
      mg or 120 mg of MDMA compounded with lactose, followed 1.5 to 2 hours later by a supplemental&#xD;
      half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per Experimental Session&#xD;
      range from 80 mg to 180 mg. This ~12-week Treatment Period is preceded by three Preparatory&#xD;
      Sessions. During the Treatment Period, each Experimental Session is followed by three&#xD;
      Integrative Sessions of non-drug psychotherapy. The Primary Outcome measure is the change in&#xD;
      Clinician Administered PTSD Scale for DSM 5 (CAPS-5) total severity scores from Baseline to&#xD;
      Primary Endpoint (Visit 19).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PTSD is a serious debilitating disorder that negatively impacts a person's daily life. PTSD&#xD;
      is a stress-related psychiatric condition that may occur following a traumatic event such as&#xD;
      war, disaster, sexual abuse, violence, terrorism, and accidents. PTSD negatively impacts a&#xD;
      person's daily life, resulting in relationship difficulties, difficulty in finding and&#xD;
      maintaining a job, reduced cognitive and psychosocial functioning, substance abuse, high-cost&#xD;
      healthcare use, and increased depression and suicide risk. Available PTSD treatments,&#xD;
      including medications and therapy, effectively treat only a fraction of people who try them&#xD;
      for adequate dose and duration. People with PTSD can be treated with psychotherapies and&#xD;
      pharmacotherapies. In the past decade, there has been a growing amount of research into&#xD;
      medications and other methods that may augment the effectiveness of psychotherapy for PTSD&#xD;
&#xD;
      3,4-methylenedioxymethamphetamine is a drug that releases serotonin, norepinephrine and&#xD;
      dopamine in the brain and indirectly increases levels of the neurohormones oxytocin, arginine&#xD;
      vasopressin and cortisol. The combined neurobiological effects of MDMA increase compassion,&#xD;
      reduce defenses and fear of emotional injury, and enhance communication and introspection.&#xD;
      MDMA produces anxiolytic and prosocial effects, which counteract avoidance and hyperarousal&#xD;
      in the context of therapy. A combined treatment of MDMA and therapy may be especially useful&#xD;
      for treating PTSD.&#xD;
&#xD;
      This multi-site, open-label, Phase 2, lead-in study assesses the safety and effect of&#xD;
      3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy in participants diagnosed with at&#xD;
      least severe posttraumatic stress disorder (PTSD). Therapy teams that have been identified&#xD;
      and trained to work on the sponsor's planned Phase 3 studies will treat at least one&#xD;
      open-label participant in this study.&#xD;
&#xD;
      This study will compare the effects of three open-label manualized Experimental Sessions of&#xD;
      psychotherapy assisted by flexible doses of MDMA. Initial doses per Experimental Session&#xD;
      include 80 mg or 120 mg of MDMA compounded with lactose, followed 1.5 to 2 hours later by a&#xD;
      supplemental half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per&#xD;
      Experimental Session range from 80 mg to 180 mg. This ~12-week Treatment Period is preceded&#xD;
      by three Preparatory Sessions. During the Treatment Period, each Experimental Session is&#xD;
      followed by three Integrative Sessions of non-drug psychotherapy. The Primary Outcome measure&#xD;
      is the change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) from Baseline to&#xD;
      Primary Endpoint (Visit 19).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 16, 2017</start_date>
  <completion_date type="Actual">August 10, 2019</completion_date>
  <primary_completion_date type="Actual">August 10, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Three sessions of MDMA-assisted therapy with flexible dose of MDMA (80 to 120 mg with optional supplemental half-dose)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>This study will be open label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline to Visit 19 in CAPS-5 Total Severity Scores</measure>
    <time_frame>Baseline to 18 weeks post-enrollment</time_frame>
    <description>The Clinician-Administered PTSD Scale for DSM-V (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Visit 19 in Adapted SDS Total Score</measure>
    <time_frame>Baseline to 18 weeks post-enrollment</time_frame>
    <description>The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment that was adapted for the purposes of this study to limit missing item-level data as per the FDA requirements and included use of the three-item mean as the total score and imputation of work-related impairment. The SDS is a 3-item scale measuring the severity of disability in the domains of work, family life/home responsibilities and social/leisure activities, with each item scored on a ten-point Likert scale from 0 ('not at all impaired') to 10 ('very severely impaired'). The SDS total score was the mean of the 3 item responses. The SDS total score ranged from 0 to 10, with higher scores indicating greater functional impairment.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>PTSD</condition>
  <arm_group>
    <arm_group_label>MDMA-assisted therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Three sessions of MDMA-assisted therapy with flexible dose of MDMA from 80 to 120 mg and optional supplemental dose half that of initial dose 1.5 to 2 hours later</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MDMA</intervention_name>
    <description>80 to 120 mg MDMA</description>
    <arm_group_label>MDMA-assisted therapy</arm_group_label>
    <other_name>3,4-methylenedioxymethamphetamine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Therapy</intervention_name>
    <description>Non-directive therapy conducted during MDMA-assisted therapy session</description>
    <arm_group_label>MDMA-assisted therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Are at least 18 years old&#xD;
&#xD;
          -  Are fluent in speaking and reading the predominantly used or recognized language of&#xD;
             the study site&#xD;
&#xD;
          -  Agree to have study visits recorded, including Experimental Sessions, Independent&#xD;
             Rater assessments, and non-drug psychotherapy sessions&#xD;
&#xD;
          -  Must provide a contact (relative, spouse, close friend or other caregiver) who is&#xD;
             willing and able to be reached by the investigators in the event of a participant&#xD;
             becoming suicidal or unreachable.&#xD;
&#xD;
        Must agree to inform the investigators within 48 hours of any medical conditions and&#xD;
        procedures&#xD;
&#xD;
          -  If of childbearing potential, must have a negative pregnancy test at study entry and&#xD;
             prior to each Experimental Session, and must agree to use adequate birth control&#xD;
             through 10 days after the last Experimental Session.&#xD;
&#xD;
          -  Must not participate in any other interventional clinical trials during the duration&#xD;
             of the study,&#xD;
&#xD;
          -  Must be willing to remain overnight at the study site after each Experimental Session&#xD;
             and be driven home after, and commit to medication dosing, therapy, and study&#xD;
             procedures&#xD;
&#xD;
          -  Meet DSM-5 Criteria for Severe PTSD&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Are not able to give adequate informed consent&#xD;
&#xD;
          -  Have uncontrolled hypertension&#xD;
&#xD;
          -  Have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration&#xD;
             of a QTc interval &gt;450 milliseconds [ms] corrected by Bazett's formula)&#xD;
&#xD;
          -  Have a history of additional risk factors for Torsade de pointes (e.g., heart failure,&#xD;
             hypokalemia, family history of Long QT Syndrome)&#xD;
&#xD;
          -  Have evidence or history of significant medical disorders&#xD;
&#xD;
          -  Have symptomatic liver disease&#xD;
&#xD;
          -  Have history of hyponatremia or hyperthermia&#xD;
&#xD;
          -  Weigh less than 48 kilograms (kg)&#xD;
&#xD;
          -  Are pregnant or nursing, or are of childbearing potential and are not practicing an&#xD;
             effective means of birth control.&#xD;
&#xD;
          -  Are abusing illegal drugs&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael C Mithoefer, MD</last_name>
    <role>Study Director</role>
    <affiliation>MAPS Public Benefit Corp.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>New School Research LLC</name>
      <address>
        <city>North Hollywood</city>
        <state>California</state>
        <zip>91601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Francisco Insight and Integration Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aguazul-Blue Water Inc.</name>
      <address>
        <city>Boulder</city>
        <state>Colorado</state>
        <zip>80302</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wholeness Center</name>
      <address>
        <city>Fort Collins</city>
        <state>Colorado</state>
        <zip>80525</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Connecticut</name>
      <address>
        <city>Farmington</city>
        <state>Connecticut</state>
        <zip>06030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ray Worthy Psychiatry LLC</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Trauma Research Foundation</name>
      <address>
        <city>Brookline</city>
        <state>Massachusetts</state>
        <zip>02446</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Affective Care</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zen Therapeutic Solutions, LLC</name>
      <address>
        <city>Mount Pleasant</city>
        <state>South Carolina</state>
        <zip>29464</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin at Madison</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>September 11, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <results_first_submitted>July 8, 2021</results_first_submitted>
  <results_first_submitted_qc>July 8, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">July 29, 2021</results_first_posted>
  <last_update_submitted>July 10, 2023</last_update_submitted>
  <last_update_submitted_qc>July 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MDMA</keyword>
  <keyword>methylenedioxymethamphetamine</keyword>
  <keyword>therapy</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>N-Methyl-3,4-methylenedioxyamphetamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>We will share outcome data appearing in any published reports upon request.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data and study-related documents will be available wehn all participants have completed the study</ipd_time_frame>
    <ipd_access_criteria>Interested persons should correspond with the central contact for the multi-site study.</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 3, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT03282123/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 3, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT03282123/SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 27, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT03282123/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were recruited through print and internet advertisements, referrals from other psychiatrists, psychotherapists, or physicians, and by word of mouth. The sponsor monitored demographics on an ongoing basis and encouraged diversity in enrollment by communicating with sites</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>MDMA-assisted Psychotherapy</title>
          <description>Three sessions of MDMA-assisted psychotherapy with flexible dose of MDMA from 80 to 120 mg and optional supplemental dose half that of initial dose 1.5 to 2 hours later&#xD;
MDMA: 80 to 120 mg MDMA&#xD;
Psychotherapy: Non-directive psychotherapy conducted during MDMA-assisted psychotherapy session</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="38"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Set</population>
      <group_list>
        <group group_id="B1">
          <title>MDMA-assisted Psychotherapy</title>
          <description>Three sessions of MDMA-assisted psychotherapy with flexible dose of MDMA from 80 to 120 mg and optional supplemental dose half that of initial dose 1.5 to 2 hours later&#xD;
MDMA: 80 to 120 mg MDMA&#xD;
Psychotherapy: Non-directive psychotherapy conducted during MDMA-assisted psychotherapy session</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="33"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36.4" spread="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline CAPS-5 Total Severity Score</title>
          <description>The Clinician-Administered PTSD Scale for DSM-V (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45.3" spread="6.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Adapted SDS Total Score</title>
          <description>The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment that was adapted for the purposes of this study. The SDS is a 3-item scale measuring the severity of disability in the domains of work, family life/home responsibilities and social/leisure activities, with each item scored on a ten-point Likert scale from 0 ('not at all impaired') to 10 ('very severely impaired'). The SDS total score ranged from 0 to 10, with higher scores indicating greater functional impairment.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.3" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to Visit 19 in CAPS-5 Total Severity Scores</title>
        <description>The Clinician-Administered PTSD Scale for DSM-V (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.</description>
        <time_frame>Baseline to 18 weeks post-enrollment</time_frame>
        <population>Safety Set</population>
        <group_list>
          <group group_id="O1">
            <title>MDMA-assisted Therapy</title>
            <description>Three sessions of MDMA-assisted therapy with flexible dose of MDMA from 80 to 120 mg and optional supplemental dose half that of initial dose 1.5 to 2 hours later&#xD;
MDMA: 80 to 120 mg MDMA&#xD;
Psychotherapy: Non-directive therapy conducted during MDMA-assisted therapy session</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Visit 19 in CAPS-5 Total Severity Scores</title>
          <description>The Clinician-Administered PTSD Scale for DSM-V (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.</description>
          <population>Safety Set</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-30.5" spread="14.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Visit 19 in Adapted SDS Total Score</title>
        <description>The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment that was adapted for the purposes of this study to limit missing item-level data as per the FDA requirements and included use of the three-item mean as the total score and imputation of work-related impairment. The SDS is a 3-item scale measuring the severity of disability in the domains of work, family life/home responsibilities and social/leisure activities, with each item scored on a ten-point Likert scale from 0 ('not at all impaired') to 10 ('very severely impaired'). The SDS total score was the mean of the 3 item responses. The SDS total score ranged from 0 to 10, with higher scores indicating greater functional impairment.</description>
        <time_frame>Baseline to 18 weeks post-enrollment</time_frame>
        <population>Safety Set</population>
        <group_list>
          <group group_id="O1">
            <title>MDMA-assisted Psychotherapy</title>
            <description>Three sessions of MDMA-assisted therapy with flexible dose of MDMA from 80 to 120 mg and optional supplemental dose half that of initial dose 1.5 to 2 hours later&#xD;
MDMA: 80 to 120 mg MDMA&#xD;
Psychotherapy: Non-directive therapy conducted during MDMA-assisted therapy session</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Visit 19 in Adapted SDS Total Score</title>
          <description>The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment that was adapted for the purposes of this study to limit missing item-level data as per the FDA requirements and included use of the three-item mean as the total score and imputation of work-related impairment. The SDS is a 3-item scale measuring the severity of disability in the domains of work, family life/home responsibilities and social/leisure activities, with each item scored on a ten-point Likert scale from 0 ('not at all impaired') to 10 ('very severely impaired'). The SDS total score was the mean of the 3 item responses. The SDS total score ranged from 0 to 10, with higher scores indicating greater functional impairment.</description>
          <population>Safety Set</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.0" spread="2.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All adverse events from enrollment to end of study (approximately 5 months)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>MDMA-assisted Psychotherapy</title>
          <description>Three sessions of MDMA-assisted psychotherapy with flexible dose of MDMA from 80 to 120 mg and optional supplemental dose half that of initial dose 1.5 to 2 hours later&#xD;
MDMA: 80 to 120 mg MDMA&#xD;
Psychotherapy: Non-directive psychotherapy conducted during MDMA-assisted psychotherapy session</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicide attempt</sub_title>
                <description>One participant with a history of suicidal ideation and two unsuccessful suicide attempts prior to the study attempted suicide 28 days after the third experimental session.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="38" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision Blurred</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Vision Impairment</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Temperature Intolerance</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Chest Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased Appetite</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in Jaw</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Muscle Tightness</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Musculoskeletal stiffness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nystagmus</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Panic Reaction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Flashback</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Bruxism</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Suicidal Ideation</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Emotional disorder</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Illusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Nightmare</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Berra Yazar-Klosinski, PhD / Chief Scientific Officer</name_or_title>
      <organization>Multidisciplinary Association for Psychedelic Studies (MAPS) Public Benefit Corporation</organization>
      <phone>(831) 429-6362</phone>
      <email>trialdata@mapsbcorp.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03282123
org study id: MP-16
nct id: NCT03282123
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This multi-site, open-label, Phase 2, lead-in study assesses the safety and effect of
      3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy in participants diagnosed with at
      least severe posttraumatic stress disorder (PTSD). Therapy teams that have been identified
      and trained to work on the sponsor's planned Phase 3 studies will treat at least one
      open-label participant in this study.

      This study will compare the effects of three open-label manualized Experimental Sessions of
      therapy assisted by flexible doses of MDMA. Initial doses per Experimental Session include 80
      mg or 120 mg of MDMA compounded with lactose, followed 1.5 to 2 hours later by a supplemental
      half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per Experimental Session
      range from 80 mg to 180 mg. This ~12-week Treatment Period is preceded by three Preparatory
      Sessions. During the Treatment Period, each Experimental Session is followed by three
      Integrative Sessions of non-drug psychotherapy. The Primary Outcome measure is the change in
      Clinician Administered PTSD Scale for DSM 5 (CAPS-5) total severity scores from Baseline to
      Primary Endpoint (Visit 19).
PTSD is a serious debilitating disorder that negatively impacts a person's daily life. PTSD
      is a stress-related psychiatric condition that may occur following a traumatic event such as
      war, disaster, sexual abuse, violence, terrorism, and accidents. PTSD negatively impacts a
      person's daily life, resulting in relationship difficulties, difficulty in finding and
      maintaining a job, reduced cognitive and psychosocial functioning, substance abuse, high-cost
      healthcare use, and increased depression and suicide risk. Available PTSD treatments,
      including medications and therapy, effectively treat only a fraction of people who try them
      for adequate dose and duration. People with PTSD can be treated with psychotherapies and
      pharmacotherapies. In the past decade, there has been a growing amount of research into
      medications and other methods that may augment the effectiveness of psychotherapy for PTSD

      3,4-methylenedioxymethamphetamine is a drug that releases serotonin, norepinephrine and
      dopamine in the brain and indirectly increases levels of the neurohormones oxytocin, arginine
      vasopressin and cortisol. The combined neurobiological effects of MDMA increase compassion,
      reduce defenses and fear of emotional injury, and enhance communication and introspection.
      MDMA produces anxiolytic and prosocial effects, which counteract avoidance and hyperarousal
      in the context of therapy. A combined treatment of MDMA and therapy may be especially useful
      for treating PTSD.

      This multi-site, open-label, Phase 2, lead-in study assesses the safety and effect of
      3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy in participants diagnosed with at
      least severe posttraumatic stress disorder (PTSD). Therapy teams that have been identified
      and trained to work on the sponsor's planned Phase 3 studies will treat at least one
      open-label participant in this study.

      This study will compare the effects of three open-label manualized Experimental Sessions of
      psychotherapy assisted by flexible doses of MDMA. Initial doses per Experimental Session
      include 80 mg or 120 mg of MDMA compounded with lactose, followed 1.5 to 2 hours later by a
      supplemental half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per
      Experimental Session range from 80 mg to 180 mg. This ~12-week Treatment Period is preceded
      by three Preparatory Sessions. During the Treatment Period, each Experimental Session is
      followed by three Integrative Sessions of non-drug psychotherapy. The Primary Outcome measure
      is the change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) from Baseline to
      Primary Endpoint (Visit 19).
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Three sessions of MDMA-assisted therapy with flexible dose of MDMA (80 to 120 mg with optional supplemental half-dose)
primary purpose: Treatment
masking: None (Open Label)
masking description: This study will be open label
measure: Change From Baseline to Visit 19 in CAPS-5 Total Severity Scores
time frame: Baseline to 18 weeks post-enrollment
description: The Clinician-Administered PTSD Scale for DSM-V (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.
measure: Change From Baseline to Visit 19 in Adapted SDS Total Score
time frame: Baseline to 18 weeks post-enrollment
description: The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment that was adapted for the purposes of this study to limit missing item-level data as per the FDA requirements and included use of the three-item mean as the total score and imputation of work-related impairment. The SDS is a 3-item scale measuring the severity of disability in the domains of work, family life/home responsibilities and social/leisure activities, with each item scored on a ten-point Likert scale from 0 ('not at all impaired') to 10 ('very severely impaired'). The SDS total score was the mean of the 3 item responses. The SDS total score ranged from 0 to 10, with higher scores indicating greater functional impairment.
arm group label: MDMA-assisted therapy
arm group type: Experimental
description: Three sessions of MDMA-assisted therapy with flexible dose of MDMA from 80 to 120 mg and optional supplemental dose half that of initial dose 1.5 to 2 hours later
intervention type: Drug
intervention name: MDMA
description: 80 to 120 mg MDMA
arm group label: MDMA-assisted therapy
other name: 3,4-methylenedioxymethamphetamine
intervention type: Behavioral
intervention name: Therapy
description: Non-directive therapy conducted during MDMA-assisted therapy session
arm group label: MDMA-assisted therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael C Mithoefer, MD
role: Study Director
affiliation: MAPS Public Benefit Corp.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: N-Methyl-3,4-methylenedioxyamphetamine
sharing ipd: Yes
ipd description: We will share outcome data appearing in any published reports upon request.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data and study-related documents will be available wehn all participants have completed the study
ipd access criteria: Interested persons should correspond with the central contact for the multi-site study.
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 