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

NCT03825965 | Completed Phase 3 DMC

• 1 other identifier: Cannabis TKA Pilot Trial
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

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.

Conditions

Knee Osteoarthritis

Keywords

Total knee arthroplasty; Cannabis; Pilot trial; Persistent post-surgical pain

Outcome Measures

Primary Outcomes (1)

• Persistent post-surgical pain (PPSP)

  Proportion of patients experiencing moderate to severe PPSP (average of pain over last week of ≥4 out of 10 on a numeric rating scale \[NRS\])

  6 months

Secondary Outcomes (9)

• Opioid use

  6 months

• Peri-operative pain intensity

  24-48 hours, 2-weeks, 6-weeks, 3-months and 6-months

• Pain interference

  24-48 hours, 2-weeks, 6-weeks, 3-months and 6-months

• Physical function

  6 months

• Mental function

  6 months

Other Outcomes (3)

• Feasibility - recruitment

  6 months

• Feasibility - retention

  6 months

• Feasibility - compliance

  6 months

Study Arms (2)

MPL-001 (CBD: THC 25:1)

EXPERIMENTAL

125mg CBD/5 mg THC oil for oral use

Drug: MPL-001 (CBD: THC 25:1)

Placebo

PLACEBO COMPARATOR

Visually identical placebo (medium chain triglyceride oil)

Drug: Placebo oil for oral use

Interventions

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

MPL-001 (CBD: THC 25:1)

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• McMaster University: lead
• St. Joseph's Healthcare Hamilton: collaborator
• Hamilton Health Sciences Corporation: collaborator

Study Sites (2)

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Marijuana Abuse

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Anthony Adili, MD, P.Eng

  McMaster University

  PRINCIPAL INVESTIGATOR

• Jason W Busse, DC, PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

• Vahid Ashoorion, MD, PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2019
• First Posted: February 1, 2019
• Study Start: May 3, 2023
• Primary Completion: February 25, 2025
• Study Completion: February 25, 2025
• Last Updated: March 19, 2025

Record last verified: 2025-03

Locations

CA (2)