<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/NCT03805750</url>
  </required_header>
  <id_info>
    <org_study_id>180414</org_study_id>
    <nct_id>NCT03805750</nct_id>
  </id_info>
  <brief_title>Trial of Cannabis for Essential Tremor</brief_title>
  <official_title>A Double-Blind, Cross-Over, Placebo- Controlled Efficacy and Tolerability Study of Oral Cannabidiol (CBD) and Tetrahydrocannabinol (THC) for Essential Tremor (ET).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>International Essential Tremor Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tilray</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Center for Medicinal Cannabis Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Diego</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 is a pilot trial to evaluate the safety and efficacy of a combined oral formulation of&#xD;
      THC and CBD in patients with Essential Tremor.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Essential tremor (ET) is the most common neurological movement disorder, affecting up to 1%&#xD;
      of the population and up to 5% of individuals over the age of 65. ET is characterized by&#xD;
      often disabling tremors that occur when an individual moves. The tremors most commonly affect&#xD;
      the hands, head, voice, and legs in order of frequency, leading to impairment in activities&#xD;
      of daily living and morbidity. No pharmacological agent has been developed for ET, though&#xD;
      existing agents such as propranolol and primidone are used off-label to reduce tremor&#xD;
      amplitude. Deep brain stimulation surgery is often reserved for only individuals with the&#xD;
      most severe tremors. Patients with ET have long reported tremor benefits with the use of&#xD;
      cannabis, though no controlled trials have been conducted. The investigators plan to conduct&#xD;
      the first double-blind, placebo-control clinical trial of cannabis in an oral capsule.&#xD;
      Various validated tremor rating methods will be used to quantify tremor severity, while&#xD;
      looking at tolerability and safety.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 22, 2019</start_date>
  <completion_date type="Actual">November 30, 2020</completion_date>
  <primary_completion_date type="Actual">September 1, 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Digital Spirography</measure>
    <time_frame>Day 22 (100 minutes post-dose)</time_frame>
    <description>The tremor mean amplitude calculated using computerized spirography to measure kinetic tremors.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Score on a Scale From Baseline of the Tremor Research Group Essential Tremor Rating Scale (TETRAS)</measure>
    <time_frame>Baseline and Day 22</time_frame>
    <description>The performance sub scale of the TETRAS will be used to measure tremor severity. The scale ranges from 0 to 60 points (0 being no tremor).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global Impression of Change</measure>
    <time_frame>Day 22</time_frame>
    <description>The Global impression of change will be calculated based on both physician and patient report. The scale ranges from a score of 1 (very much improved) to 7 (very much worse) with a score of 4 indicating 'no change'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Reporting Adverse Events Based on Common Terminology Criteria</measure>
    <time_frame>Days 1, 3, 6, 22</time_frame>
    <description>Side effects survey</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants at Risk for Suicide Based on Columbia-Suicide Severity Rating Scale (C-SSRS)</measure>
    <time_frame>Day 22</time_frame>
    <description>This is a scale looking at risk assessment of suicidality. The presence of any positive responses will lead to further evaluation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With New Study-related Electrocardiogram (EKG) Abnormalities</measure>
    <time_frame>Day 22</time_frame>
    <description>Electrocardiographic changes from baseline measures will trigger further evaluation. EKG's will be rated as normal/abnormal relative to the baseline EKG reading, and abnormal findings will be rated as clinically significant/not clinically significant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accelerometry-based Assessment of Tremor Severity</measure>
    <time_frame>Baseline and Day 22</time_frame>
    <description>The spectral power density measure of accelerometry data to measure will serve as a measure of tremor severity, comparing tremor amplitude from this digital biomarker at the time of the primary outcome to the same measure at baseline.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Essential Tremor</condition>
  <arm_group>
    <arm_group_label>CBD/THC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment arm consisting of Tetrahydrocannabinol (5mg/capsule) and Cannabidiol (100mg/capsule).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matched placebo capsule with no active ingredients.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CBD/THC</intervention_name>
    <description>Oral formulation of combined Cannabidiol (CBD) and Tetrahydrocannabinol (THC).</description>
    <arm_group_label>CBD/THC</arm_group_label>
    <other_name>marijuana</other_name>
    <other_name>cannabis</other_name>
    <other_name>cannabidiol</other_name>
    <other_name>tetrahydrocannabinol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>Matched Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of ET by a Movement Disorder Neurologist&#xD;
&#xD;
          -  Stable dose of tremor medication for a period of at least 6 weeks prior to screening&#xD;
&#xD;
          -  Tremor in the arms&#xD;
&#xD;
          -  Tremor(s) is/are moderately severe (amplitude of at least 1cm)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant non-ET related abnormal findings on neurological exam&#xD;
&#xD;
          -  Tremor at rest, or other features suggestive of Parkinson disease&#xD;
&#xD;
          -  Diagnosis of dementia&#xD;
&#xD;
          -  Pregnant or nursing&#xD;
&#xD;
          -  Childbearing potential and unable or unwilling to use contraception during course of&#xD;
             the trial&#xD;
&#xD;
          -  On medications known to interact with the study drug&#xD;
&#xD;
          -  Current or prior history of alcohol or substance abuse&#xD;
&#xD;
          -  Recent exposure to primidone (within the past 21 days) or benzodiazepines (such as&#xD;
             Valium, Ativan or Klonopin), ketoconazole, ritonavir, clarithromycin, rifampin,&#xD;
             carbamazepine, St. Johns Wort, digoxin or other medications known to affect your liver&#xD;
             enzymes (within the past 7 days).&#xD;
&#xD;
          -  Unwilling to abstain from consuming grapefruits, grapefruit juice or grapefruit&#xD;
             containing products.&#xD;
&#xD;
          -  Taking medications such as warfarin, cyclosporine, and amphotericin B that are highly&#xD;
             protein-bound&#xD;
&#xD;
          -  Do not wish to take a cannabis-derived agent&#xD;
&#xD;
          -  Allergy or sensitivity to sorbitol, xylitol, stevia or other natural sweeteners&#xD;
&#xD;
          -  Allergy or sensitivity to cannabis&#xD;
&#xD;
          -  Used cannabis or a cannabis-derived product (such as CBD oil) within the past 4 weeks&#xD;
             or plan to use it during this research study.&#xD;
&#xD;
          -  Diagnosis of a psychiatric disorder (e.g., mania, bipolar depressive disorder,&#xD;
             schizophrenia, schizoaffective disorder, or other major psychiatric disorder)&#xD;
&#xD;
          -  Current or prior history of suicidal thoughts and/or behavior&#xD;
&#xD;
          -  Active medical problem affecting the immune system, liver, gastrointestinal tract,&#xD;
             lungs, heart, endocrine system (such as diabetes and/or thyroid), and/or a blood&#xD;
             clotting disorder&#xD;
&#xD;
          -  Current infection&#xD;
&#xD;
          -  Reduced kidney function (GFR &lt;60)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fatta Nahab, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UCSD</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California San Diego</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://tremor.cmcr.ucsd.edu</url>
    <description>Study Information</description>
  </link>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <results_first_submitted>February 15, 2022</results_first_submitted>
  <results_first_submitted_qc>October 9, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">October 13, 2022</results_first_posted>
  <last_update_submitted>October 9, 2022</last_update_submitted>
  <last_update_submitted_qc>October 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Diego</investigator_affiliation>
    <investigator_full_name>Fatta B Nahab</investigator_full_name>
    <investigator_title>Associate Professor of Neurosciences</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tremor</mesh_term>
    <mesh_term>Essential Tremor</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dronabinol</mesh_term>
    <mesh_term>Cannabidiol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 30, 2013</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT03805750/Prot_SAP_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This is a cross-over design where each subject receives both a placebo and treatment arm in blinded random order.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>CBD/THC First Then Placebo</title>
          <description>After randomization, each patient will receive study medication in two study periods. Each study period includes 1-week titration, 2-week treatment, and 1-week tapering. There is a 3-week washout period between the two study periods. During the titration period, patients will have a starting dose of 1 capsule (placebo or 5mg THC/100mg CBD) per day; 2 capsules per day on day 3; 3 capsules per day on day 6. If the patient or investigator feel that the higher study drug dose of 3 caps per day is causing troublesome side effects, the dosage may be lowered to 2 caps per day. Patients will continue on this target dose during the 2-week treatment and then gradually taper from medication over one week. Patients will crossover to the alternate treatment after a 3-week washout period.</description>
        </group>
        <group group_id="P2">
          <title>Placebo First Then CBD/THC</title>
          <description>After randomization, each patient will receive study medication in two study periods. Each study period includes 1-week titration, 2-week treatment, and 1-week tapering. There is a 3-week washout period between the two study periods. During the titration period, patients will have a starting dose of 1 capsule (placebo or 5mg THC/100mg CBD) per day; 2 capsules per day on day 3; 3 capsules per day on day 6. If the patient or investigator feel that the higher study drug dose of 3 caps per day is causing troublesome side effects, the dosage may be lowered to 2 caps per day. Patients will continue on this target dose during the 2-week treatment and then gradually taper from medication over one week. Patients will crossover to the alternate treatment after a 3-week washout period.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First Intervention - 4 Weeks</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Second Intervention - 4 Weeks</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Participants</title>
          <description>After randomization, each patient will receive study medication in two study periods. Each study period includes 1-week titration, 2-week treatment, and 1-week tapering. There is a 3-week washout period between the two study periods. During the titration period, patients will have a starting dose of 1 capsule (placebo or 5mg THC/100mg CBD) per day; 2 capsules per day on day 3; 3 capsules per day on day 6. If the patient or investigator feel that the higher study drug dose of 3 caps per day is causing troublesome side effects, the dosage may be lowered to 2 caps per day. Patients will continue on this target dose during the 2-week treatment and then gradually taper from medication over one week. Patients will crossover to the alternate treatment after a 3-week washout period.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="7"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="67.0" spread="11.3"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Digital Spirography</title>
        <description>The tremor mean amplitude calculated using computerized spirography to measure kinetic tremors.</description>
        <time_frame>Day 22 (100 minutes post-dose)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CBD/THC</title>
            <description>Treatment arm&#xD;
CBD/THC: Oral formulation of CBD and THC.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo oral capsule: Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Digital Spirography</title>
          <description>The tremor mean amplitude calculated using computerized spirography to measure kinetic tremors.</description>
          <units>millimeters of tremor amplitude</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.04" spread="0.57"/>
                    <measurement group_id="O2" value="1.00" spread="0.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Score on a Scale From Baseline of the Tremor Research Group Essential Tremor Rating Scale (TETRAS)</title>
        <description>The performance sub scale of the TETRAS will be used to measure tremor severity. The scale ranges from 0 to 60 points (0 being no tremor).</description>
        <time_frame>Baseline and Day 22</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CBD/THC</title>
            <description>Treatment arm&#xD;
CBD/THC: Oral formulation of CBD and THC.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo oral capsule: Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Score on a Scale From Baseline of the Tremor Research Group Essential Tremor Rating Scale (TETRAS)</title>
          <description>The performance sub scale of the TETRAS will be used to measure tremor severity. The scale ranges from 0 to 60 points (0 being no tremor).</description>
          <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="5"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.07" spread="5.71"/>
                    <measurement group_id="O2" value="-10.3" spread="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Global Impression of Change</title>
        <description>The Global impression of change will be calculated based on both physician and patient report. The scale ranges from a score of 1 (very much improved) to 7 (very much worse) with a score of 4 indicating 'no change'.</description>
        <time_frame>Day 22</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CBD/THC</title>
            <description>Treatment arm&#xD;
CBD/THC: Oral formulation of CBD and THC.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo oral capsule: Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Global Impression of Change</title>
          <description>The Global impression of change will be calculated based on both physician and patient report. The scale ranges from a score of 1 (very much improved) to 7 (very much worse) with a score of 4 indicating 'no change'.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Clinical Global Impression of Change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" lower_limit="3" upper_limit="4"/>
                    <measurement group_id="O2" value="4" lower_limit="2" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Patient Global Impression of Change</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" lower_limit="3" upper_limit="4"/>
                    <measurement group_id="O2" value="4" lower_limit="2.5" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Reporting Adverse Events Based on Common Terminology Criteria</title>
        <description>Side effects survey</description>
        <time_frame>Days 1, 3, 6, 22</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CBD/THC</title>
            <description>Treatment arm&#xD;
CBD/THC: Oral formulation of CBD and THC.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo oral capsule: Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Reporting Adverse Events Based on Common Terminology Criteria</title>
          <description>Side effects survey</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ringing in ears</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Numbness/tingling</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspnea on exertion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Watery eyes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Runny nose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Decreased concentration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleepiness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Insomnia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Increased sleepiness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dizziness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Memory problems</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Imbalance</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mild headache</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Groggy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tired</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Thumb pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Headache</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lightheaded</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Felt high</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Decreased libido</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diarrhea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dry mouth</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Euphoria</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Feels relaxed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Increased thirst</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Felt buzzed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Quivering voice</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visual slowing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants at Risk for Suicide Based on Columbia-Suicide Severity Rating Scale (C-SSRS)</title>
        <description>This is a scale looking at risk assessment of suicidality. The presence of any positive responses will lead to further evaluation.</description>
        <time_frame>Day 22</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CBD/THC</title>
            <description>Treatment arm&#xD;
CBD/THC: Oral formulation of CBD and THC.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo oral capsule: Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants at Risk for Suicide Based on Columbia-Suicide Severity Rating Scale (C-SSRS)</title>
          <description>This is a scale looking at risk assessment of suicidality. The presence of any positive responses will lead to further evaluation.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With New Study-related Electrocardiogram (EKG) Abnormalities</title>
        <description>Electrocardiographic changes from baseline measures will trigger further evaluation. EKG's will be rated as normal/abnormal relative to the baseline EKG reading, and abnormal findings will be rated as clinically significant/not clinically significant.</description>
        <time_frame>Day 22</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CBD/THC</title>
            <description>Treatment arm&#xD;
CBD/THC: Oral formulation of CBD and THC.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo oral capsule: Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With New Study-related Electrocardiogram (EKG) Abnormalities</title>
          <description>Electrocardiographic changes from baseline measures will trigger further evaluation. EKG's will be rated as normal/abnormal relative to the baseline EKG reading, and abnormal findings will be rated as clinically significant/not clinically significant.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.52</p_value>
            <method>Regression, Logistic</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Accelerometry-based Assessment of Tremor Severity</title>
        <description>The spectral power density measure of accelerometry data to measure will serve as a measure of tremor severity, comparing tremor amplitude from this digital biomarker at the time of the primary outcome to the same measure at baseline.</description>
        <time_frame>Baseline and Day 22</time_frame>
        <population>Participants in both treatment arms will undergone tremor measurement using accelerometry as a surrogate of tremor severity.</population>
        <group_list>
          <group group_id="O1">
            <title>CBD/THC</title>
            <description>Treatment arm&#xD;
CBD/THC: Oral formulation of CBD and THC.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo oral capsule: Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Accelerometry-based Assessment of Tremor Severity</title>
          <description>The spectral power density measure of accelerometry data to measure will serve as a measure of tremor severity, comparing tremor amplitude from this digital biomarker at the time of the primary outcome to the same measure at baseline.</description>
          <population>Participants in both treatment arms will undergone tremor measurement using accelerometry as a surrogate of tremor severity.</population>
          <units>Proportion of baseline spectral power</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.012" spread="0.03"/>
                    <measurement group_id="O2" value="0.007" spread="0.011"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Over the course of the study period (77 days).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>CBD/THC</title>
          <description>Treatment arm&#xD;
CBD/THC: Oral formulation of CBD and THC.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo oral capsule: Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <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="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>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="7" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Lightheadedness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ringing in ears</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Watery eyes</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Visual slowing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Increased thirst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased libido</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Feeling relaxed</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Numbness/tingling</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Decreased concentration</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Sleepiness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Increased sleepiness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Memory problems</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Imbalance</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Mild headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Grogginess/cognitive slowing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Tiredness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Feeling high/intoxication</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Felt buzzed</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Euphoria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea on exertion</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Runny nose</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Quivering voice</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Thumb pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>F.B. Nahab MD</name_or_title>
      <organization>University of California San Diego</organization>
      <phone>858-822-6683</phone>
      <email>fnahab@health.ucsd.edu</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/NCT03805750
org study id: 180414
nct id: NCT03805750
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a pilot trial to evaluate the safety and efficacy of a combined oral formulation of
      THC and CBD in patients with Essential Tremor.
Essential tremor (ET) is the most common neurological movement disorder, affecting up to 1%
      of the population and up to 5% of individuals over the age of 65. ET is characterized by
      often disabling tremors that occur when an individual moves. The tremors most commonly affect
      the hands, head, voice, and legs in order of frequency, leading to impairment in activities
      of daily living and morbidity. No pharmacological agent has been developed for ET, though
      existing agents such as propranolol and primidone are used off-label to reduce tremor
      amplitude. Deep brain stimulation surgery is often reserved for only individuals with the
      most severe tremors. Patients with ET have long reported tremor benefits with the use of
      cannabis, though no controlled trials have been conducted. The investigators plan to conduct
      the first double-blind, placebo-control clinical trial of cannabis in an oral capsule.
      Various validated tremor rating methods will be used to quantify tremor severity, while
      looking at tolerability and safety.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Digital Spirography
time frame: Day 22 (100 minutes post-dose)
description: The tremor mean amplitude calculated using computerized spirography to measure kinetic tremors.
measure: Change in Score on a Scale From Baseline of the Tremor Research Group Essential Tremor Rating Scale (TETRAS)
time frame: Baseline and Day 22
description: The performance sub scale of the TETRAS will be used to measure tremor severity. The scale ranges from 0 to 60 points (0 being no tremor).
measure: Global Impression of Change
time frame: Day 22
description: The Global impression of change will be calculated based on both physician and patient report. The scale ranges from a score of 1 (very much improved) to 7 (very much worse) with a score of 4 indicating 'no change'.
measure: Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
time frame: Days 1, 3, 6, 22
description: Side effects survey
measure: Number of Participants at Risk for Suicide Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
time frame: Day 22
description: This is a scale looking at risk assessment of suicidality. The presence of any positive responses will lead to further evaluation.
measure: Number of Participants With New Study-related Electrocardiogram (EKG) Abnormalities
time frame: Day 22
description: Electrocardiographic changes from baseline measures will trigger further evaluation. EKG's will be rated as normal/abnormal relative to the baseline EKG reading, and abnormal findings will be rated as clinically significant/not clinically significant.
measure: Accelerometry-based Assessment of Tremor Severity
time frame: Baseline and Day 22
description: The spectral power density measure of accelerometry data to measure will serve as a measure of tremor severity, comparing tremor amplitude from this digital biomarker at the time of the primary outcome to the same measure at baseline.
arm group label: CBD/THC
arm group type: Experimental
description: Treatment arm consisting of Tetrahydrocannabinol (5mg/capsule) and Cannabidiol (100mg/capsule).
arm group label: Placebo
arm group type: Placebo Comparator
description: Matched placebo capsule with no active ingredients.
intervention type: Drug
intervention name: CBD/THC
description: Oral formulation of combined Cannabidiol (CBD) and Tetrahydrocannabinol (THC).
arm group label: CBD/THC
other name: marijuana
other name: cannabis
other name: cannabidiol
other name: tetrahydrocannabinol
intervention type: Drug
intervention name: Placebo oral capsule
description: Matched Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Fatta Nahab, MD
role: Principal Investigator
affiliation: UCSD
facility: 
country: United States
url: http://tremor.cmcr.ucsd.edu
description: Study Information
responsible party type: Principal Investigator
investigator affiliation: University of California, San Diego
investigator full name: Fatta B Nahab
investigator title: Associate Professor of Neurosciences
mesh term: Tremor
mesh term: Essential Tremor
mesh term: Dronabinol
mesh term: Cannabidiol
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 