Clinical trial NCT03825965: Cannabinoids vs. Placebo on Persistent Post-surgical Pain Following TKA: A Pilot RCT
Official title: The Effect of Cannabinoids vs. Placebo on Persistent Post-surgical Pain Following Total Knee Arthroplasty: A Multicenter, Randomized Pilot Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Knee Osteoarthritis
Keywords: Total knee arthroplasty
Cannabis
Pilot trial
Persistent post-surgical pain
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: St. Joseph's Healthcare Hamilton
name: Hamilton Health Sciences Corporation
First posted: 2019-02-01
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Persistent post-surgical pain (PPSP)
timeFrame: 6 months
Secondary outcomes:
measure: Opioid use
timeFrame: 6 months
measure: Peri-operative pain intensity
timeFrame: 24-48 hours, 2-weeks, 6-weeks, 3-months and 6-months
measure: Pain interference
timeFrame: 24-48 hours, 2-weeks, 6-weeks, 3-months and 6-months
measure: Physical function
timeFrame: 6 months
measure: Mental function
timeFrame: 6 months
measure: Return to function
timeFrame: 6 months
measure: Insomnia
timeFrame: 6 months
measure: Anxiety and depression
timeFrame: 6 months
measure: Safety - Adverse events
timeFrame: 6 months
Other outcomes:
measure: Feasibility - recruitment
timeFrame: 6 months
measure: Feasibility - retention
timeFrame: 6 months
measure: Feasibility - compliance
timeFrame: 6 months
Locations:
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
Study officials:
affiliation: McMaster University
name: Anthony Adili, MD, P.Eng
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: Jason W Busse, DC, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: Vahid Ashoorion, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: