<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/NCT03825965</url>
  </required_header>
  <id_info>
    <org_study_id>Cannabis TKA Pilot Trial</org_study_id>
    <nct_id>NCT03825965</nct_id>
  </id_info>
  <brief_title>Cannabinoids vs. Placebo on Persistent Post-surgical Pain Following TKA: A Pilot RCT</brief_title>
  <official_title>The Effect of Cannabinoids vs. Placebo on Persistent Post-surgical Pain Following Total Knee Arthroplasty: A Multicenter, Randomized Pilot Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>McMaster University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>St. Joseph's Healthcare Hamilton</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hamilton Health Sciences Corporation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>McMaster University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Each year, approximately 75,000 Canadians undergo knee replacement surgery, and up to 25%&#xD;
      develop persistent post-surgical pain. Persistent post-surgical pain is associated with&#xD;
      depression, anxiety, unemployment, and reduced quality of life. Chronic pain after surgery is&#xD;
      often managed with opioid therapy, which typically provides only modest benefits and is&#xD;
      associated with rare but serious adverse events, such as overdose and death. A number of&#xD;
      studies have found that greater pain just before and after knee replacement surgery is&#xD;
      associated with the development of chronic pain, suggesting that reducing peri-operative pain&#xD;
      may help prevent persistent post-surgical pain.&#xD;
&#xD;
      Medicinal cannabis has begun to emerge as a potential therapy for pain reduction, and&#xD;
      produces effects largely due to 2 active components: (1) cannabidiol (CBD), and (2)&#xD;
      tetrahydrocannabinol (THC). Studies of CBD have shown analgesic, anti-inflammatory, and&#xD;
      anti-anxiety properties, but without the psychoactive effects (feeling 'high') that THC&#xD;
      produces. This study will assess the feasibility of a definitive trial to explore whether&#xD;
      adding CBD dominant vs. placebo to usual care before and after surgery can reduce the rate of&#xD;
      persistent post-surgical pain after total knee replacement. This study will randomize 40&#xD;
      patients to receive either CBD dominant or placebo, and follow them for six months to confirm&#xD;
      our ability to recruit patients, adhere to protocol, and capture full outcome data for at&#xD;
      least 85% of patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Approximately 25% of patients develop persistent post-surgical pain (PPSP) after undergoing&#xD;
      total knee arthroplasty (TKA), and higher pre-surgery and acute post-operative pain are&#xD;
      associated with this outcome. Medicinal cannabis has anti-inflammatory and analgesic&#xD;
      properties and may reduce peri-operative pain and the rate of PPSP following TKA. Cannabidiol&#xD;
      (CBD) is the active ingredient of interest because of its anti-inflammatory effects and lack&#xD;
      of psychoactive effects seen with tetrahydrocannabinol (THC). The primary objective of this&#xD;
      pilot trial is to assess the feasibility of a definitive trial to determine the effect of&#xD;
      medicinal cannabis, versus placebo, on the proportion of patients experiencing PPSP following&#xD;
      TKA. The primary objective of the definitive trial is to determine if medicinal cannabis&#xD;
      add-on therapy, versus placebo, reduces the proportion of patients experiencing PPSP at 6&#xD;
      months following TKA. The secondary objectives of the definitive trial are to determine if&#xD;
      medicinal cannabis, versus placebo, reduces opioid use, reduces peri-operative pain&#xD;
      interference, improves physical functioning, mental functioning, return to function, anxiety&#xD;
      and depression, and sleep. The effect of medicinal cannabis, versus placebo, on the incidence&#xD;
      of adverse events at 6 months post-surgery will also be examined. In this blinded&#xD;
      multi-centre pilot trial, 40 patients will be randomized to receive either oral capsules of&#xD;
      CBD oil or visually identical placebo in addition to standard of care pain medications.&#xD;
      Participants will be followed for 6 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 3, 2023</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Anticipated">August 2024</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Persistent post-surgical pain (PPSP)</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion of patients experiencing moderate to severe PPSP (average of pain over last week of ≥4 out of 10 on a numeric rating scale [NRS])</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Opioid use</measure>
    <time_frame>6 months</time_frame>
    <description>Use of opioids (mean morphine equivalent dose [MED] change)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peri-operative pain intensity</measure>
    <time_frame>24-48 hours, 2-weeks, 6-weeks, 3-months and 6-months</time_frame>
    <description>Peri-operative pain measured on an 11-point NRS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain interference</measure>
    <time_frame>24-48 hours, 2-weeks, 6-weeks, 3-months and 6-months</time_frame>
    <description>Pain interference measured by the Brief Pain Inventory (BPI-SF)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical function</measure>
    <time_frame>6 months</time_frame>
    <description>Physical component summary (PCS) score of the SF-12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mental function</measure>
    <time_frame>6 months</time_frame>
    <description>Mental component summary (MCS) score of the SF-12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Return to function</measure>
    <time_frame>6 months</time_frame>
    <description>Return to 80% of pre-injury function (work, leisure, home activities)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insomnia</measure>
    <time_frame>6 months</time_frame>
    <description>Insomnia symptoms on the Insomnia Severity Index (ISI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anxiety and depression</measure>
    <time_frame>6 months</time_frame>
    <description>Anxiety and depression on the Hospital Anxiety and Depression Scale (HADS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety - Adverse events</measure>
    <time_frame>6 months</time_frame>
    <description>Serious and non-serious adverse events</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Feasibility - recruitment</measure>
    <time_frame>6 months</time_frame>
    <description>Ability to recruit 40 patients</description>
  </other_outcome>
  <other_outcome>
    <measure>Feasibility - retention</measure>
    <time_frame>6 months</time_frame>
    <description>Ability to follow 85% of patients</description>
  </other_outcome>
  <other_outcome>
    <measure>Feasibility - compliance</measure>
    <time_frame>6 months</time_frame>
    <description>Patient compliance with the study treatment (75% of patients comply with 75% of the study doses)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Knee Osteoarthritis</condition>
  <arm_group>
    <arm_group_label>MPL-001 (CBD: THC 25:1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>125mg CBD/5 mg THC oil for oral use</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Visually identical placebo (medium chain triglyceride oil)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MPL-001 (CBD: THC 25:1)</intervention_name>
    <description>25:1 cannabidiol (CBD): tetrahydrocannabinol (THC) oral formulation, with a concentration of 50 mg/mL CBD and 2 mg/mL THC, oil- Liquid for oral use</description>
    <arm_group_label>MPL-001 (CBD: THC 25:1)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oil for oral use</intervention_name>
    <description>Placebo is Medium-chain triglycerides oil with identical features (in appearance, flavour, and odour) to the MPL-001 oil.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients undergoing TKA aged 18 or older&#xD;
&#xD;
          -  Cognitive ability and English-language skills required to complete outcome measures&#xD;
&#xD;
          -  Provision of informed consent&#xD;
&#xD;
          -  Successful completion of the run-in period&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe cardio-respiratory disease (For operationalizing: ASA 4/NYHA 4)&#xD;
&#xD;
          -  Substance use disorder based on DSM-V criteria&#xD;
&#xD;
          -  Allergy or intolerance to cannabis, cannabis derivatives, or other ingredients of the&#xD;
             study drug&#xD;
&#xD;
          -  Patients who are pregnant, planning to be pregnant, or breastfeeding&#xD;
&#xD;
          -  Revision TKA&#xD;
&#xD;
          -  Bilateral TKA&#xD;
&#xD;
          -  Presenting for their pre-surgical consultation less than 4 weeks before surgery&#xD;
&#xD;
          -  Patients with a chronic pain condition affecting the knee (other than osteoarthritis)&#xD;
             (e.g.: patients with knee pain due to fibromyalgia or chronic pain syndrome will be&#xD;
             excluded)&#xD;
&#xD;
          -  Unwilling or unable to follow the study protocol&#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>Anthony Adili, MD, P.Eng</last_name>
    <role>Principal Investigator</role>
    <affiliation>McMaster University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jason W Busse, DC, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>McMaster University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vahid Ashoorion, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>McMaster University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Anthony Adili, MD, P.Eng</last_name>
    <phone>(905) 522-1155</phone>
    <phone_ext>36062</phone_ext>
    <email>adilia@mcmaster.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Kim Madden, PhD</last_name>
    <phone>(289) 237-7380</phone>
    <email>maddenk@mcmaster.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>St. Joseph's Healthcare Hamilton</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8N 4A6</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anthony Adili, MD, P.Eng</last_name>
      <phone>(905) 522-1155</phone>
      <phone_ext>36062</phone_ext>
      <email>adilia@mcmaster.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>St. Michael's Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5B 1W8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Amit Atrey, MD</last_name>
      <phone>1(416)864-5342</phone>
      <email>amit.atrey@unityhealth.to</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 30, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>June 29, 2023</last_update_submitted>
  <last_update_submitted_qc>June 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Total knee arthroplasty</keyword>
  <keyword>Cannabis</keyword>
  <keyword>Pilot trial</keyword>
  <keyword>Persistent post-surgical pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03825965
org study id: Cannabis TKA Pilot Trial
nct id: NCT03825965
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Each year, approximately 75,000 Canadians undergo knee replacement surgery, and up to 25%
      develop persistent post-surgical pain. Persistent post-surgical pain is associated with
      depression, anxiety, unemployment, and reduced quality of life. Chronic pain after surgery is
      often managed with opioid therapy, which typically provides only modest benefits and is
      associated with rare but serious adverse events, such as overdose and death. A number of
      studies have found that greater pain just before and after knee replacement surgery is
      associated with the development of chronic pain, suggesting that reducing peri-operative pain
      may help prevent persistent post-surgical pain.

      Medicinal cannabis has begun to emerge as a potential therapy for pain reduction, and
      produces effects largely due to 2 active components: (1) cannabidiol (CBD), and (2)
      tetrahydrocannabinol (THC). Studies of CBD have shown analgesic, anti-inflammatory, and
      anti-anxiety properties, but without the psychoactive effects (feeling 'high') that THC
      produces. This study will assess the feasibility of a definitive trial to explore whether
      adding CBD dominant vs. placebo to usual care before and after surgery can reduce the rate of
      persistent post-surgical pain after total knee replacement. This study will randomize 40
      patients to receive either CBD dominant or placebo, and follow them for six months to confirm
      our ability to recruit patients, adhere to protocol, and capture full outcome data for at
      least 85% of patients.
Approximately 25% of patients develop persistent post-surgical pain (PPSP) after undergoing
      total knee arthroplasty (TKA), and higher pre-surgery and acute post-operative pain are
      associated with this outcome. Medicinal cannabis has anti-inflammatory and analgesic
      properties and may reduce peri-operative pain and the rate of PPSP following TKA. Cannabidiol
      (CBD) is the active ingredient of interest because of its anti-inflammatory effects and lack
      of psychoactive effects seen with tetrahydrocannabinol (THC). The primary objective of this
      pilot trial is to assess the feasibility of a definitive trial to determine the effect of
      medicinal cannabis, versus placebo, on the proportion of patients experiencing PPSP following
      TKA. The primary objective of the definitive trial is to determine if medicinal cannabis
      add-on therapy, versus placebo, reduces the proportion of patients experiencing PPSP at 6
      months following TKA. The secondary objectives of the definitive trial are to determine if
      medicinal cannabis, versus placebo, reduces opioid use, reduces peri-operative pain
      interference, improves physical functioning, mental functioning, return to function, anxiety
      and depression, and sleep. The effect of medicinal cannabis, versus placebo, on the incidence
      of adverse events at 6 months post-surgery will also be examined. In this blinded
      multi-centre pilot trial, 40 patients will be randomized to receive either oral capsules of
      CBD oil or visually identical placebo in addition to standard of care pain medications.
      Participants will be followed for 6 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Persistent post-surgical pain (PPSP)
time frame: 6 months
description: Proportion of patients experiencing moderate to severe PPSP (average of pain over last week of ≥4 out of 10 on a numeric rating scale [NRS])
measure: Opioid use
time frame: 6 months
description: Use of opioids (mean morphine equivalent dose [MED] change)
measure: Peri-operative pain intensity
time frame: 24-48 hours, 2-weeks, 6-weeks, 3-months and 6-months
description: Peri-operative pain measured on an 11-point NRS
measure: Pain interference
time frame: 24-48 hours, 2-weeks, 6-weeks, 3-months and 6-months
description: Pain interference measured by the Brief Pain Inventory (BPI-SF)
measure: Physical function
time frame: 6 months
description: Physical component summary (PCS) score of the SF-12
measure: Mental function
time frame: 6 months
description: Mental component summary (MCS) score of the SF-12
measure: Return to function
time frame: 6 months
description: Return to 80% of pre-injury function (work, leisure, home activities)
measure: Insomnia
time frame: 6 months
description: Insomnia symptoms on the Insomnia Severity Index (ISI)
measure: Anxiety and depression
time frame: 6 months
description: Anxiety and depression on the Hospital Anxiety and Depression Scale (HADS)
measure: Safety - Adverse events
time frame: 6 months
description: Serious and non-serious adverse events
measure: Feasibility - recruitment
time frame: 6 months
description: Ability to recruit 40 patients
measure: Feasibility - retention
time frame: 6 months
description: Ability to follow 85% of patients
measure: Feasibility - compliance
time frame: 6 months
description: Patient compliance with the study treatment (75% of patients comply with 75% of the study doses)
arm group label: MPL-001 (CBD: THC 25:1)
arm group type: Experimental
description: 125mg CBD/5 mg THC oil for oral use
arm group label: Placebo
arm group type: Placebo Comparator
description: Visually identical placebo (medium chain triglyceride oil)
intervention type: Drug
intervention name: MPL-001 (CBD: THC 25:1)
description: 25:1 cannabidiol (CBD): tetrahydrocannabinol (THC) oral formulation, with a concentration of 50 mg/mL CBD and 2 mg/mL THC, oil- Liquid for oral use
arm group label: MPL-001 (CBD: THC 25:1)
intervention type: Drug
intervention name: Placebo oil for oral use
description: Placebo is Medium-chain triglycerides oil with identical features (in appearance, flavour, and odour) to the MPL-001 oil.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anthony Adili, MD, P.Eng
role: Principal Investigator
affiliation: McMaster University
last name: Jason W Busse, DC, PhD
role: Principal Investigator
affiliation: McMaster University
last name: Vahid Ashoorion, MD, PhD
role: Principal Investigator
affiliation: McMaster University
last name: Anthony Adili, MD, P.Eng
phone: (905) 522-1155
phone ext: 36062
email: adilia@mcmaster.ca
last name: Kim Madden, PhD
phone: (289) 237-7380
email: maddenk@mcmaster.ca
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
country: Canada
responsible party type: Sponsor
mesh term: Pain, Postoperative
sharing ipd: Undecided