Cannabidiol for Bilateral Total Knee Arthroplasty
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Ora-sweet SF
|
Other: Ora-sweet SF
Ora-sweet SF placebo
|
| Experimental: 400mg cannabidiol
|
Drug: cannabidiol
Epidiolex (cannabidiol) oral solution
Other Names:
|
| Experimental: 800mg cannabidiol
|
Drug: cannabidiol
Epidiolex (cannabidiol) oral solution
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Cumulative Opioid Usage in First 72 hours Postoperatively [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 Outcome Measures
- Pharmacokinetics of CBD [0, 1, 2, 3, 4, 6 hours after medication administration]
Levels of CBD in the blood. This is measured using blood draws and lab analysis.
- Levels of Plasma Inflammatory Marker Interleukin-6 [Preoperative, Postoperative day 1]
Interleukin-6 (IL6) is an inflammatory marker found in plasma. The levels of IL6 are measured using blood draws and lab analysis.
- NRS Pain at rest [Preoperatively; postoperatively in the PACU, morning of postoperative day (POD) 1,2,3,4,7 and at 3 months]
Pain at rest measured using numerical rating scale(NRS) from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.
- NRS Pain with movement [Preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months]
Pain with movement using numerical rating scale(NRS) from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.
- Brief Pain Inventory Short Form [Preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months]
Brief Pain inventory short form measures the severity of pain and its impact on function. It measures pain from 0-10 0 being no pain whatsoever to 10 being the worst pain imaginable. It measures impact on function from 0-10, 0 being no impact whatsoever to 10 being completely impactful.
- Incidence of adverse events [Postoperatively in the PACU; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months]
Adverse events, including allergic reactions, pyrexia (fever), somnolence (excessive sleepiness), GI problems (upset stomach, diarrhea), dry mouth, escalation of post-operative opioid requirement
- Opioid related Symptom Distress Scale (ORSDS) [Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months]
ORSDS measures opioid related side effects. There are 13 side effects with 3 subcategories (severity, frequency, bothersomeness) each with 5 different responses (scored 0-4).
- Anxiety levels [Preoperatively; Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months]
Hospital Anxiety and Depression Scale (HADS) asks 14 questions, 7 about anxiety and 7 about depression. Responses are scored from 0-3. Responses between the two categories are summed and scoring is as follows: 0-7 = normal, 8-10=borderlines abnormal, 11-21=abnormal
- Cumulative inpatient analgesic use (non-opioid) [POD0 - POD3]
Total non-opioid medication usage
- Opioid & non-opioid analgesic consumption [At hospital discharge to POD7 and at 3 months]
Total opioid & non-opioid medication usage
- Hospital length of stay [End of surgery to hospital discharge]
Length of stay measured in hours
- Blinding Assessment [POD4]
Patients are asked which treatment they think they received. The correctness of their guesses is then measured using the bang-blinding index to see if patients were able to accurately guess which treatment they received. It is measured on a scale of -1 to 1. Scores closer to 0 indicate better blinding, or patients not being able to guess their treatment
- Time to reach discharge physical therapy goals [At hospital discharge - up to 3 days after surgery]
Physical therapy goals for total knee replacement include walking 100 feet, going up and down 4 stairs, and independent transfer (meaning they can move from a lying to standing position independently). Patients need to complete these goals before being discharged
- Range of motion [preoperatively, 6 weeks postoperatively.]
Range of motion, or extension and flexion of the knees, are measured preoperatively and at the patients' 6 week surgeon visit. It is measured in degrees
- Sleep quality and duration [POD0 - POD3]
Sleep quality assessed by actigraphy using ActiGraph wGT3X-BT activity monitor
- Sleep quality [preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months]
Sleep quality assessed by Leeds sleep evaluation questionnaire (LSEQ). Responses to 10 questions will be measured on a slider scale ranging from 0-100.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 18 to 70
-
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
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Weight < 40kg
-
Planned use of general anesthesia
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Contraindication to major components of study protocol
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Cannabis or cannabinoid use within the past 3 months (recreational and/or medical)
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Use or ingestion of hemp seeds or hemp oil in any form within the past 30 days
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Chronic opioid use (>3 months)
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Coumadin use
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Current use of SSRI or SNRIs
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History of substance abuse or dependence
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Active or history of major psychiatric illness
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Severe cardiovascular disorder
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Severe hepatic or renal insufficiency (transaminase levels above ULN)
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History of epilepsy
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Diagnosis of rheumatic disease, autoimmune disease, or immunodeficiency (e.g. rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, multiple sclerosis, etc.)
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Use of valproate or clobazam
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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)
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Active use of steroids - oral steroids upon admission
-
Stress dose steroids
-
Non-English speakers
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital for Special Surgery | New York | New York | United States | 10021 |
Sponsors and Collaborators
- Hospital for Special Surgery, New York
Investigators
- Principal Investigator: Alexandra Sideris, PhD, Hospital for Special Surgery, New York
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2019-1688