Back to resultsCannabidiol for Bilateral Total Knee Arthroplasty
Primary Purpose
Pain, Postoperative, Opioid Use, Knee Osteoarthritis
Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
cannabidiol
Ora-sweet SF
Sponsored by
About this trial
This is an interventional treatment trial for Pain, Postoperative
Eligibility 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
- 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
Sites / Locations
- Hospital for Special SurgeryRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Ora-sweet SF
400mg cannabidiol
800mg cannabidiol
Arm Description
Outcomes
Primary Outcome Measures
Cumulative Opioid Usage in First 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
Levels of CBD in the blood. This is measured using blood draws and lab analysis.
Levels of Plasma Inflammatory Marker Interleukin-6
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
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
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
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
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)
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
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)
Total non-opioid medication usage
Opioid & non-opioid analgesic consumption
Total opioid & non-opioid medication usage
Hospital length of stay
Length of stay measured in hours
Blinding Assessment
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
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
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
Sleep quality assessed by actigraphy using ActiGraph wGT3X-BT activity monitor
Sleep quality
Sleep quality assessed by Leeds sleep evaluation questionnaire (LSEQ). Responses to 10 questions will be measured on a slider scale ranging from 0-100.
Full Information
NCT ID
NCT04749628
First Posted
February 5, 2021
Last Updated
August 28, 2023
Sponsor
Hospital for Special Surgery, New York
1. Study Identification
Unique Protocol Identification Number
NCT04749628
Brief Title
Cannabidiol for Bilateral Total Knee Arthroplasty
Official Title
Effects of Cannabidiol (CBD) Oral Solution in Patients Undergoing Bilateral Total Knee Arthroplasty: a Randomized, Controlled, Parallel, Triple Blind, Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 2, 2022 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
May 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital for Special Surgery, New York
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Postoperative, Opioid Use, Knee Osteoarthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Ora-sweet SF
Arm Type
Placebo Comparator
Arm Title
400mg cannabidiol
Arm Type
Experimental
Arm Title
800mg cannabidiol
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
cannabidiol
Other Intervention Name(s)
Epidiolex
Intervention Description
Epidiolex (cannabidiol) oral solution
Intervention Type
Other
Intervention Name(s)
Ora-sweet SF
Intervention Description
Ora-sweet SF placebo
Primary Outcome Measure Information:
Title
Cumulative Opioid Usage in First 72 hours Postoperatively
Description
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
Time Frame
0-72 hours postoperatively
Secondary Outcome Measure Information:
Title
Pharmacokinetics of CBD
Description
Levels of CBD in the blood. This is measured using blood draws and lab analysis.
Time Frame
0, 1, 2, 3, 4, 6 hours after medication administration
Title
Levels of Plasma Inflammatory Marker Interleukin-6
Description
Interleukin-6 (IL6) is an inflammatory marker found in plasma. The levels of IL6 are measured using blood draws and lab analysis.
Time Frame
Preoperative, Postoperative day 1
Title
NRS Pain at rest
Description
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.
Time Frame
Preoperatively; postoperatively in the PACU, morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Title
NRS Pain with movement
Description
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.
Time Frame
Preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Title
Brief Pain Inventory Short Form
Description
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.
Time Frame
Preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Title
Incidence of adverse events
Description
Adverse events, including allergic reactions, pyrexia (fever), somnolence (excessive sleepiness), GI problems (upset stomach, diarrhea), dry mouth, escalation of post-operative opioid requirement
Time Frame
Postoperatively in the PACU; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Title
Opioid related Symptom Distress Scale (ORSDS)
Description
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).
Time Frame
Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Title
Anxiety levels
Description
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
Time Frame
Preoperatively; Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Title
Cumulative inpatient analgesic use (non-opioid)
Description
Total non-opioid medication usage
Time Frame
POD0 - POD3
Title
Opioid & non-opioid analgesic consumption
Description
Total opioid & non-opioid medication usage
Time Frame
At hospital discharge to POD7 and at 3 months
Title
Hospital length of stay
Description
Length of stay measured in hours
Time Frame
End of surgery to hospital discharge
Title
Blinding Assessment
Description
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 Frame
POD4
Title
Time to reach discharge physical therapy goals
Description
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
Time Frame
At hospital discharge - up to 3 days after surgery
Title
Range of motion
Description
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
Time Frame
preoperatively, 6 weeks postoperatively.
Title
Sleep quality and duration
Description
Sleep quality assessed by actigraphy using ActiGraph wGT3X-BT activity monitor
Time Frame
POD0 - POD3
Title
Sleep quality
Description
Sleep quality assessed by Leeds sleep evaluation questionnaire (LSEQ). Responses to 10 questions will be measured on a slider scale ranging from 0-100.
Time Frame
preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
William Chan, MEng
Phone
917-260-4788
Email
chanw@hss.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexandra Sideris, PhD
Organizational Affiliation
Hospital for Special Surgery, New York
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital for Special Surgery
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
William Chan, MEng
Phone
917-260-4788
Email
chanw@hss.edu
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared.
IPD Sharing Time Frame
Beginning 9 months and ending 36 months following article publication
IPD Sharing Access Criteria
For researchers who provide a methodologically sound proposal and analyses to achieve aims in the approved proposal. Proposals should be directed to siderisa@hss.edu. To gain access, data requestors will need to sign a data access agreement.
Learn more about this trial
Cannabidiol for Bilateral Total Knee Arthroplasty
We'll reach out to this number within 24 hrs