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OpenTrials
Completed

NCT Number: NCT04749628

Cannabidiol for Bilateral Total Knee Arthroplasty

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.

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Key information

Conditions

Pain, Postoperative Arthritis Joint Diseases Knee Osteoarthritis Musculoskeletal Diseases Neurologic Manifestations Opioid Use Osteoarthritis Osteoarthritis, Knee Pain Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Complications Rheumatic Diseases Signs and Symptoms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Hospital for Special Surgery

New York, 10021, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Cannabidiol

Drug

Epidiolex (cannabidiol) oral solution

Other names: Epidiolex

Ora-sweet SF

Other

Ora-sweet SF placebo

Primary outcomes

  1. 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

  1. Pharmacokinetics of CBD

    Time frame: 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.

  2. Levels of Plasma Inflammatory Marker Interleukin-6

    Time frame: 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.

    The outcome measure below indicates the difference between IL6 levels on postoperative day 1 and preoperative.

  3. NRS Pain at Rest

    Time frame: 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.

  4. NRS Pain With Movement

    Time frame: 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.

  5. Brief Pain Inventory Short Form

    Time frame: 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.

  6. Incidence of Adverse Events

    Time frame: 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

  7. Opioid Related Symptom Distress Scale (ORSDS)

    Time frame: Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months

    Opioid related Symptom Distress Scale (ORSDS) measures opioid related side effects. There are 12 side effects with 3 subcategories (severity, frequency, bothersomeness) each with 5 different responses (scored 0-4 with higher scores indicating worse symptoms). The ORSDS composite score was calculated by averaging the scores for each symptom.

  8. Anxiety Levels

    Time frame: 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

  9. Cumulative Inpatient Analgesic Use (Non-opioid)

    Time frame: POD0 - POD3

    Total non-opioid medication usage

  10. Number of Participants With Opioid and Non-opioid Medication Use

    Time frame: POD0 - POD3

    Opioid and non-opioid medication use by count (%)

  11. Opioid & Non-opioid Analgesic Consumption

    Time frame: At hospital discharge to POD7

    Total opioid (morphine milligram equivalents) & non-opioid medication usage

  12. Number of Participants With Opioid and Non-opioid Medication Use

    Time frame: POD0 to POD7 and 3 months

    Opioid & non-opioid medication use by count (%)

  13. Hospital Length of Stay

    Time frame: At hospital discharge

    Length of stay measured in hours from end of surgery to hospital discharge

  14. Blinding Assessment

    Time frame: 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. The index (number) is calculated as a group-level summary statistic, computed from the distribution of guesses across all participants in a group.

  15. Time to Reach Discharge Physical Therapy Goals

    Time frame: At hospital discharge

    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

  16. Range of Motion

    Time frame: 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

  17. Actigraphy Sleep Efficiency

    Time frame: POD0 - POD3

    Sleep quality assessed by actigraphy using ActiGraph wGT3X-BT activity monitor. Higher sleep efficiency indicates better sleep quality. Sleep efficiency was calculated between the hours of 11pm and 6am each night.

  18. Actigraphy Sleep Time

    Time frame: POD0 - POD3

    Sleep quality assessed by actigraphy using ActiGraph wGT3X-BT activity monitor. Higher sleep time indicates better sleep quality. Total sleep time was calculated between the hours of 11pm and 6am each night.

  19. Sleep Quality

    Time frame: 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. Higher scores indicate better outcomes.

    Getting to Sleep domain scores were calculated by averaging the responses to Questions 1-3 regarding falling asleep.

    Quality of Sleep domain scores were calculated by averaging the responses to Questions 4-5 regarding quality of sleep.

    Awake Following Sleep domain scores were calculated by averaging the responses to Questions 6-7 regarding awakening from sleep.

    Behaviour Following Wakening domain scores were calculated by averaging the responses to Questions 8-10 regarding feeling, balance, and coordination upon awakening.

Sponsors and collaborators

Lead sponsor

Hospital for Special Surgery, New York

Other

Registry information

Official study title

Effects of Cannabidiol (CBD) Oral Solution in Patients Undergoing Bilateral Total Knee Arthroplasty: a Randomized, Controlled, Parallel, Triple Blind, Pilot Study

Important dates

Study start
2022
Primary completion
2024
Study completion
2025
First posted
Feb 11, 2021
Registry last updated
May 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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