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

NCT ID: NCT03825965

Last Updated: 2025-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-03
• Study Completion Date: 2025-02-25

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.

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.

Conditions

Knee Osteoarthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

MPL-001 (CBD: THC 25:1)

125mg CBD/5 mg THC oil for oral use

Group Type: EXPERIMENTAL

MPL-001 (CBD: THC 25:1)

Intervention Type: 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

Visually identical placebo (medium chain triglyceride oil)

Group Type: PLACEBO_COMPARATOR

Placebo oil for oral use

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Joseph's Healthcare Hamilton

OTHER

Sponsor Role: collaborator

Hamilton Health Sciences Corporation

OTHER

Sponsor Role: collaborator

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anthony Adili, MD, P.Eng

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Jason W Busse, DC, PhD

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Vahid Ashoorion, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

Cannabis TKA Pilot Trial

Identifier Type: -

Identifier Source: org_study_id