<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/NCT03247244</url>
  </required_header>
  <id_info>
    <org_study_id>14-7726</org_study_id>
    <nct_id>NCT03247244</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Cannabis in Tourette Syndrome</brief_title>
  <official_title>A Double-blind, Randomized, Placebo-controlled Crossover Pilot Trial of Medical Cannabis in Adults With Tourette Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Health Network, Toronto</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      For many individuals with Tourette syndrome (TS), available medications do not help with&#xD;
      their symptoms, or cause significant side effects. Two small controlled trials have&#xD;
      investigated the effect of oral delta-9-tetrahydrocannabinol (THC), a principal psychoactive&#xD;
      ingredient of cannabis, in TS patients. While these trials have shown promising results, the&#xD;
      effect sizes were not as large and consistent as those reported by patients with regards to&#xD;
      inhaled cannabis (smoked or vaporized). Indeed, based on anecdotal evidence, patients have&#xD;
      much greater improvement in their symptoms using inhaled cannabis than using cannabinoid&#xD;
      pharmaceuticals. However, there have been no controlled trials of inhaled medical cannabis&#xD;
      for TS to date. Furthermore, various medical cannabis products are authorized in Canada with&#xD;
      different contents of THC and cannabidiol (CBD), another primary cannabinoid. No data exists&#xD;
      regarding the dosing, efficacy and safety of these products in the treatment of TS. To gather&#xD;
      such data, a double-blind, randomized, crossover pilot trial will be conducted to compare the&#xD;
      efficacy and safety of three vaporized medical cannabis products with different THC and CBD&#xD;
      contents, as well as placebo, in adults with TS. As well, the PK/PD profile of THC and CBD of&#xD;
      the products will be assessed and correlated with tic symptoms&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Recruitment/enrollment took too long&#xD;
  </why_stopped>
  <start_date type="Actual">January 15, 2018</start_date>
  <completion_date type="Actual">January 27, 2020</completion_date>
  <primary_completion_date type="Actual">June 6, 2019</primary_completion_date>
  <phase>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>
    <intervention_model_description>There are four treatment schemes. All subjects will be randomized in a 1:1:1:1 ratio to one of the four treatment schemes. Participants will receive a single dose of each of the 3 cannabis products + placebo, with the order determine by their assigned treatment arm.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>The participants, investigators and analysts will be masked as to the treatment arm and product of each participant and visit. Only the pharmacists will be aware of the strain.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Modified Rush Video-Based Tic Rating Scale</measure>
    <time_frame>10 minutes</time_frame>
    <description>Can be used to assess changes in frequency and severity of tics</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Marijuana Effect Expectancy Questionnaire (MEEQ)</measure>
    <time_frame>6 hours</time_frame>
    <description>To assess tolerability of cannabis products</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Area under the plasma concentration versus time curve of CBD and 11-OH-THC</measure>
    <time_frame>6 hours</time_frame>
    <description>Determine a temporal relationship between changes in THC/CBD plasma concentrations and tic severity</description>
  </other_outcome>
  <other_outcome>
    <measure>Premonitory Urge for Tics Scale (PUTS)</measure>
    <time_frame>1 hour</time_frame>
    <description>Assesses the intensity of premonitory urges</description>
  </other_outcome>
  <other_outcome>
    <measure>Clinical Global Impression- Improvement Scale (CGI-I)</measure>
    <time_frame>1 hour</time_frame>
    <description>Assesses how improved symptoms are after an intervention</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Tourette Syndrome</condition>
  <arm_group>
    <arm_group_label>1</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Three cannabis drug product formulations with different THC and CBD contents and placebo will be used in the following order: A (THC 10%, CBD &lt;0.5%), B (THC 8.6%, CBD 8.6%), C (THC 0.6%, CBD 14%) and placebo D (THC &lt;0.3%, CBD &lt;0.3%).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Three cannabis drug product formulations with different THC and CBD contents and placebo will be used in the following order: B (THC 8.6%, CBD 8.6%), placebo D (THC &lt;0.3%, CBD &lt;0.3%), A (THC 10%, CBD &lt;0.5%), C (THC 0.6%, CBD 14%).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Three cannabis drug product formulations with different THC and CBD contents and placebo will be used in the following order: C (THC 0.6%, CBD 14%), A (THC 10%, CBD &lt;0.5%), placebo D (THC &lt;0.3%, CBD &lt;0.3%), B (THC 8.6%, CBD 8.6%).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>4</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Three cannabis drug product formulations with different THC and CBD contents and placebo will be used in the following order: placebo D (THC &lt;0.3%, CBD &lt;0.3%), C (THC 0.6%, CBD 14%), B (THC 8.6%, CBD 8.6%), A (THC 10%, CBD &lt;0.5%).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cannabis</intervention_name>
    <description>THC 10%, CBD &lt;0.5%</description>
    <arm_group_label>1</arm_group_label>
    <arm_group_label>2</arm_group_label>
    <arm_group_label>3</arm_group_label>
    <arm_group_label>4</arm_group_label>
    <other_name>Marijuana</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cannabis</intervention_name>
    <description>THC 8.6%, CBD 8.6%</description>
    <arm_group_label>1</arm_group_label>
    <arm_group_label>2</arm_group_label>
    <arm_group_label>3</arm_group_label>
    <arm_group_label>4</arm_group_label>
    <other_name>Marijuana</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cannabis</intervention_name>
    <description>THC 0.6%, CBD 14%</description>
    <arm_group_label>1</arm_group_label>
    <arm_group_label>2</arm_group_label>
    <arm_group_label>3</arm_group_label>
    <arm_group_label>4</arm_group_label>
    <other_name>Marijuana</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female adult, 18-65 years of age (inclusive) at the time of signing the&#xD;
             informed consent.&#xD;
&#xD;
          -  The subject meets current DSM-5 diagnostic criteria for TS[6], diagnosed by a&#xD;
             neuropsychiatrist with expertise in TS and related conditions.&#xD;
&#xD;
          -  YGTSS-TTS ≥16, frequency subscore = 5 and intensity subscore ≥ 2. In addition, tic&#xD;
             free intervals do not last more than two minutes based on both self-reporting and&#xD;
             observation by clinician at both screening and Week 0 (randomization). This&#xD;
             requirement is for the purpose of minimizing the potential for floor effects given the&#xD;
             relatively short window for assessing effect on symptoms in this single-dose trial.&#xD;
&#xD;
          -  The subject is able and willing to refrain from using any non-study cannabis during&#xD;
             the screening and treatment phases of the study.&#xD;
&#xD;
          -  Females of childbearing potential (defined by menarche and not having undergone&#xD;
             surgical sterilization/hysterectomy) must have a negative pregnancy test, must be&#xD;
             practicing acceptable double-barrier methods of contraception (or can confirm&#xD;
             abstinence at each scheduled visit), and must not be breast feeding.&#xD;
&#xD;
          -  Written informed consent must be obtained from the subject prior to the initiation of&#xD;
             any protocol-required procedures.&#xD;
&#xD;
          -  The subject is able to comprehend and satisfactorily comply with the protocol&#xD;
             requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  • The subject and/or his/her family have a history of psychosis, schizophrenia or&#xD;
             bipolar disorder.&#xD;
&#xD;
               -  Sexually active females of childbearing potential who will not commit to&#xD;
                  utilizing 2 of the approved birth control methods or who will not remain&#xD;
                  abstinent during the trial; Females who are breast-feeding and/or who have a&#xD;
                  positive serum pregnancy test result prior at the time of screening.&#xD;
&#xD;
               -  The subject represents a significant risk of committing suicide (current suicide&#xD;
                  plan or attempt in past 2 years) or committing homicide.&#xD;
&#xD;
               -  The subject has a history of serious head injury, seizure disorder, or&#xD;
                  developmental delay (intelligence quotient≤85).&#xD;
&#xD;
               -  The subject has either of: cardiovascular disease; respiratory disease such as&#xD;
                  chronic obstructive pulmonary disease (COPD) or lung cancer (asthma is not an&#xD;
                  exclusionary criterion); hepatitis.&#xD;
&#xD;
               -  The subject has a current or past history of substance abuse within the last 5&#xD;
                  years, with the exception of cannabis.&#xD;
&#xD;
               -  The subject is using cannabis regularly for the treatment of TS.&#xD;
&#xD;
               -  The subject has any abnormal laboratory tests and vital sign results which in the&#xD;
                  investigator's judgment is medically significant and would impact the safety of&#xD;
                  the subject or the interpretation of the study results.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul Sandor, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Health Network, Toronto</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Toronto Western Hospital - Tourette Syndrome Neurodevelopmental Clinic</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5T2S8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>July 25, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>January 21, 2021</last_update_submitted>
  <last_update_submitted_qc>January 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cannabis</keyword>
  <keyword>Tics</keyword>
  <keyword>Tourette Syndrome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tourette Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03247244
org study id: 14-7726
nct id: NCT03247244
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
For many individuals with Tourette syndrome (TS), available medications do not help with
      their symptoms, or cause significant side effects. Two small controlled trials have
      investigated the effect of oral delta-9-tetrahydrocannabinol (THC), a principal psychoactive
      ingredient of cannabis, in TS patients. While these trials have shown promising results, the
      effect sizes were not as large and consistent as those reported by patients with regards to
      inhaled cannabis (smoked or vaporized). Indeed, based on anecdotal evidence, patients have
      much greater improvement in their symptoms using inhaled cannabis than using cannabinoid
      pharmaceuticals. However, there have been no controlled trials of inhaled medical cannabis
      for TS to date. Furthermore, various medical cannabis products are authorized in Canada with
      different contents of THC and cannabidiol (CBD), another primary cannabinoid. No data exists
      regarding the dosing, efficacy and safety of these products in the treatment of TS. To gather
      such data, a double-blind, randomized, crossover pilot trial will be conducted to compare the
      efficacy and safety of three vaporized medical cannabis products with different THC and CBD
      contents, as well as placebo, in adults with TS. As well, the PK/PD profile of THC and CBD of
      the products will be assessed and correlated with tic symptoms
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: There are four treatment schemes. All subjects will be randomized in a 1:1:1:1 ratio to one of the four treatment schemes. Participants will receive a single dose of each of the 3 cannabis products + placebo, with the order determine by their assigned treatment arm.
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: The participants, investigators and analysts will be masked as to the treatment arm and product of each participant and visit. Only the pharmacists will be aware of the strain.
measure: Modified Rush Video-Based Tic Rating Scale
time frame: 10 minutes
description: Can be used to assess changes in frequency and severity of tics
measure: The Marijuana Effect Expectancy Questionnaire (MEEQ)
time frame: 6 hours
description: To assess tolerability of cannabis products
measure: Area under the plasma concentration versus time curve of CBD and 11-OH-THC
time frame: 6 hours
description: Determine a temporal relationship between changes in THC/CBD plasma concentrations and tic severity
measure: Premonitory Urge for Tics Scale (PUTS)
time frame: 1 hour
description: Assesses the intensity of premonitory urges
measure: Clinical Global Impression- Improvement Scale (CGI-I)
time frame: 1 hour
description: Assesses how improved symptoms are after an intervention
arm group label: 1
arm group type: Other
description: Three cannabis drug product formulations with different THC and CBD contents and placebo will be used in the following order: A (THC 10%, CBD <0.5%), B (THC 8.6%, CBD 8.6%), C (THC 0.6%, CBD 14%) and placebo D (THC <0.3%, CBD <0.3%).
arm group label: 2
arm group type: Other
description: Three cannabis drug product formulations with different THC and CBD contents and placebo will be used in the following order: B (THC 8.6%, CBD 8.6%), placebo D (THC <0.3%, CBD <0.3%), A (THC 10%, CBD <0.5%), C (THC 0.6%, CBD 14%).
arm group label: 3
arm group type: Other
description: Three cannabis drug product formulations with different THC and CBD contents and placebo will be used in the following order: C (THC 0.6%, CBD 14%), A (THC 10%, CBD <0.5%), placebo D (THC <0.3%, CBD <0.3%), B (THC 8.6%, CBD 8.6%).
arm group label: 4
arm group type: Other
description: Three cannabis drug product formulations with different THC and CBD contents and placebo will be used in the following order: placebo D (THC <0.3%, CBD <0.3%), C (THC 0.6%, CBD 14%), B (THC 8.6%, CBD 8.6%), A (THC 10%, CBD <0.5%).
intervention type: Drug
intervention name: Cannabis
description: THC 10%, CBD <0.5%
arm group label: 1
arm group label: 2
arm group label: 3
arm group label: 4
other name: Marijuana
intervention type: Drug
intervention name: Cannabis
description: THC 8.6%, CBD 8.6%
arm group label: 1
arm group label: 2
arm group label: 3
arm group label: 4
other name: Marijuana
intervention type: Drug
intervention name: Cannabis
description: THC 0.6%, CBD 14%
arm group label: 1
arm group label: 2
arm group label: 3
arm group label: 4
other name: Marijuana
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Paul Sandor, MD
role: Principal Investigator
affiliation: University Health Network, Toronto
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Tourette Syndrome
mesh term: Syndrome