Effects of Cannabidiol (CBD) Oral Solution in Patients Undergoing Bilateral Total Knee Arthroplasty: a Randomized, Controlled, Parallel, Triple Blind, Pilot Study
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Enrollment
- 37
- Locations
- 2
- Primary Endpoint
- Cumulative Opioid Usage in First 72 hours Postoperatively
Study Overview
Brief Summary
In light of the opioid epidemic and evidence suggesting that cannabis may be opioid-sparing, we are in a unique position to conduct a novel, high-impact study that would set the stage for future RCTs examining the effects of a nonintoxicating and nonaddictive cannabinoid in an orthopedic patient population. Epidiolex®, an oral cannabidiol (CBD) solution, is the first ever cannabis-derived medication to be approved by the Food & Drug Administration. Our aim is to conduct a pilot study using a placebo oral solution, 400mg and 800mg Epidiolex® to gather data on its effects on patients undergoing bilateral total knee arthroplasty (BTKA). We will be estimating whether Epidiolex® is associated with minimal opioid use and adequate analgesia. We will also assess its tolerability, pharmacokinetics, and effects on inflammatory markers in the perioperative setting.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 18 to 75
- •Scheduled for same-day bilateral total knee replacements with participating surgeons
- •American Society of Anesthesiologists (ASA) Physical Status 1 or 2
Exclusion Criteria
- •ASA 3 and higher
- •Weight < 40kg
- •Planned use of general anesthesia
- •Contraindication to major components of study protocol
- •Cannabis or cannabinoid use within the past 3 months (recreational and/or medical)
- •Use or ingestion of hemp seeds or hemp oil in any form within the past 30 days
- •Chronic opioid use (>3 months)
- •Coumadin use
- •Current use of SSRI or SNRIs
- •History of substance abuse or dependence
- •Active or history of major psychiatric illness
- •Severe cardiovascular disorder
- •Severe hepatic or renal insufficiency (transaminase levels above ULN)
- •History of epilepsy
- •Diagnosis of rheumatic disease, autoimmune disease, or immunodeficiency (e.g. rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, multiple sclerosis, etc.)
- •Use of valproate or clobazam
- •Known or suspected hypersensitivity, allergy, or contraindication to cannabinoids or any of the excipients in the study medications (i.e. sesame oil, sucralose, strawberry flavor)
- •Active use of steroids - oral steroids upon admission
- •Stress dose steroids
- •Non-English speakers
- •Planned discharge to home without caregiver(s)
Arms & Interventions
Ora-sweet SF
Intervention: Ora-sweet SF (Other)
400mg cannabidiol
Intervention: cannabidiol (Drug)
800mg cannabidiol
Intervention: cannabidiol (Drug)
Outcomes
Primary Outcomes
Cumulative Opioid Usage in First 72 hours Postoperatively
Time Frame: 0-72 hours postoperatively
Cumulative opioid usage over the first 72 hours after surgery. Measured in morphine equivalents (ME), a scale that measure opioid usage among all opioid medications
Secondary Outcomes
- Hospital length of stay(End of surgery to hospital discharge)
- Pharmacokinetics of CBD(0, 1, 2, 3, 4, 6 hours after medication administration)
- Opioid related Symptom Distress Scale (ORSDS)(Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months)
- Levels of Plasma Inflammatory Marker Interleukin-6(Preoperative, Postoperative day 1)
- NRS Pain at rest(Preoperatively; postoperatively in the PACU, morning of postoperative day (POD) 1,2,3,4,7 and at 3 months)
- NRS Pain with movement(Preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months)
- Incidence of adverse events(Postoperatively in the PACU; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months)
- Sleep quality(preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months)
- Brief Pain Inventory Short Form(Preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months)
- Cumulative inpatient analgesic use (non-opioid)(POD0 - POD3)
- Opioid & non-opioid analgesic consumption(At hospital discharge to POD7 and at 3 months)
- Time to reach discharge physical therapy goals(At hospital discharge - up to 3 days after surgery)
- Range of motion(preoperatively, 6 weeks postoperatively.)
- Sleep quality and duration(POD0 - POD3)
- Anxiety levels(Preoperatively; Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months)
- Blinding Assessment(POD4)