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NCT Number: NCT03825965

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

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.

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Key information

Conditions

Knee Osteoarthritis Arthritis Chemically-Induced Disorders Joint Diseases Marijuana Abuse Mental Disorders Musculoskeletal Diseases Osteoarthritis Osteoarthritis, Knee Rheumatic Diseases Substance-Related Disorders

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

MPL-001 (CBD: THC 25:1)

Drug

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 oil for oral use

Drug

Placebo is Medium-chain triglycerides oil with identical features (in appearance, flavour, and odour) to the MPL-001 oil.

Primary outcomes

  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 outcomes

  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 outcomes

  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)

Sponsors and collaborators

Lead sponsor

McMaster University

Other

Collaborators

  • Hamilton Health Sciences Corporation
  • St. Joseph's Healthcare Hamilton

Registry information

Official study title

The Effect of Cannabinoids vs. Placebo on Persistent Post-surgical Pain Following Total Knee Arthroplasty: A Multicenter, Randomized Pilot Trial

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Feb 1, 2019
Registry last updated
Mar 19, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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