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Cannabinoids vs. Placebo on Persistent Post-surgical Pain Following TKA: A Pilot RCT

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ClinicalTrials.gov Identifier: NCT03825965
Recruitment Status : Not yet recruiting
First Posted : February 1, 2019
Last Update Posted : July 15, 2022
Sponsor:
Collaborators:
St. Joseph's Healthcare Hamilton
Hamilton Health Sciences Corporation
Information provided by (Responsible Party):
McMaster University

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Knee Osteoarthritis Drug: MPL-001 (CBD: THC 25:1) Drug: Placebo oil for oral use Phase 3

Detailed Description:
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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Cannabinoids vs. Placebo on Persistent Post-surgical Pain Following Total Knee Arthroplasty: A Multicenter, Randomized Pilot Trial
Estimated Study Start Date : August 2022
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : August 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: MPL-001 (CBD: THC 25:1)
125mg CBD/5 mg THC oil for oral use
 Drug: MPL-001 (CBD: THC 25:1)
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
Placebo Comparator: Placebo
Visually identical placebo (medium chain triglyceride oil)
 Drug: Placebo oil for oral use
Placebo is Medium-chain triglycerides oil with identical features (in appearance, flavour, and odour) to the MPL-001 oil.


Outcome Measures
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Primary Outcome Measures :
  1. Persistent post-surgical pain (PPSP) [ Time Frame: 6 months ]
    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])


Secondary Outcome Measures :
  1. Opioid use [ Time Frame: 6 months ]
    Use of opioids (mean morphine equivalent dose [MED] change)

  2. Peri-operative pain intensity [ Time Frame: 24-48 hours, 2-weeks, 6-weeks, 3-months and 6-months ]
    Peri-operative pain measured on an 11-point NRS

  3. Pain interference [ Time Frame: 24-48 hours, 2-weeks, 6-weeks, 3-months and 6-months ]
    Pain interference measured by the Brief Pain Inventory (BPI-SF)

  4. Physical function [ Time Frame: 6 months ]
    Physical component summary (PCS) score of the SF-12

  5. Mental function [ Time Frame: 6 months ]
    Mental component summary (MCS) score of the SF-12

  6. Return to function [ Time Frame: 6 months ]
    Return to 80% of pre-injury function (work, leisure, home activities)

  7. Insomnia [ Time Frame: 6 months ]
    Insomnia symptoms on the Insomnia Severity Index (ISI)

  8. Anxiety and depression [ Time Frame: 6 months ]
    Anxiety and depression on the Hospital Anxiety and Depression Scale (HADS)

  9. Safety - Adverse events [ Time Frame: 6 months ]
    Serious and non-serious adverse events


Other Outcome Measures:
  1. Feasibility - recruitment [ Time Frame: 6 months ]
    Ability to recruit 40 patients

  2. Feasibility - retention [ Time Frame: 6 months ]
    Ability to follow 85% of patients

  3. Feasibility - compliance [ Time Frame: 6 months ]
    Patient compliance with the study treatment (75% of patients comply with 75% of the study doses)


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients undergoing TKA aged 18 or older
  • Cognitive ability and English-language skills required to complete outcome measures
  • Provision of informed consent
  • Successful completion of the run-in period

Exclusion Criteria:

  • Severe cardio-respiratory disease (For operationalizing: ASA 4/NYHA 4)
  • Substance use disorder based on DSM-V criteria
  • Allergy or intolerance to cannabis, cannabis derivatives, or other ingredients of the study drug
  • Patients who are pregnant, planning to be pregnant, or breastfeeding
  • Revision TKA
  • Bilateral TKA
  • Presenting for their pre-surgical consultation less than 4 weeks before surgery
  • Patients with a chronic pain condition affecting the knee (other than osteoarthritis) (e.g.: patients with knee pain due to fibromyalgia or chronic pain syndrome will be excluded)
  • Unwilling or unable to follow the study protocol
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03825965


Contacts
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Contact: Anthony Adili, MD, P.Eng (905) 522-1155 ext 36062 adilia@mcmaster.ca
Contact: Kim Madden, PhD (289) 237-7380 maddenk@mcmaster.ca

Locations
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Canada, Ontario
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, Canada, L8N 4A6
Contact: Anthony Adili, MD, P.Eng    (905) 522-1155 ext 36062    adilia@mcmaster.ca   
Hamilton Health Sciences - Juravinski Hospital
Hamilton, Ontario, Canada, L8V 1C3
Contact: Mitchell Winemaker, MD    905-570-8884    winemakm@hhsc.ca   
Sponsors and Collaborators
McMaster University
St. Joseph's Healthcare Hamilton
Hamilton Health Sciences Corporation
Investigators
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Principal Investigator: Anthony Adili, MD, P.Eng McMaster University
Principal Investigator: Jason W Busse, DC, PhD McMaster University
Principal Investigator: Vahid Ashoorion, MD, PhD McMaster University
More Information
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Responsible Party: McMaster University
ClinicalTrials.gov Identifier: NCT03825965    
Other Study ID Numbers: Cannabis TKA Pilot Trial
First Posted: February 1, 2019    Key Record Dates
Last Update Posted: July 15, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by McMaster University:
Total knee arthroplasty
Cannabis
Pilot trial
Persistent post-surgical pain
Additional relevant MeSH terms:
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Osteoarthritis, Knee
Pain, Postoperative
Osteoarthritis
Arthritis
Joint Diseases
Musculoskeletal Diseases
 Rheumatic Diseases
Postoperative Complications
Pathologic Processes
Pain
Neurologic Manifestations