Knee Replacement SurgeryPhase 2CORKNCT06234631
Cannabidiol for Postoperative Opioid Reduction in Primary Total Knee Arthroplasty
A Phase 2 study testing Epidiolex oral solution in people with Knee Replacement Surgery and Osteoarthritis, Knee, run by Chad Brummett at 2 sites in United States.
Trial summary
The goal of this study is to better understand how daily treatment with cannabidiol (CBD) affects the need for opioid pain medication, as well as pain, inflammation and other related symptoms, after knee replacement surgery. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Knee Replacement Surgery, Osteoarthritis, Knee
- What is being tested?
- Epidiolex oral solution
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 380 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 Mar 2024to Jan 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to read, understand, and sign the informed consent (English)
- Willingness to participate in all study measures and restrictions, including patient-reported outcomes and longitudinal follow-up
- Scheduled for surgery: primary total knee arthroplasty
- Primary diagnosis of osteoarthritis of the surgical knee
- Individuals of reproductive potential must agree to use acceptable birth control (defined in manual of operating procedures). This includes currently practicing an effective form of two types of birth control for women of childbearing potential, which are defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly from the screening visit until 28 days after the last study drug administration.
- Participants must also agree not to donate sperm or eggs during study drug administration
- Ability to take and to swallow the study medication and be willing to adhere to the treatment regimen
- Agreement to adhere to Lifestyle Considerations (see protocol) throughout study duration
Who cannot join
- Revision or bilateral total knee arthroplasty
- Individuals receiving or actively applying for worker's compensation or disability and other aspects associated with potential secondary gain (postoperative disability for recovery is permitted)
- Severe physical impairment or clinically significant illness (e.g., blindness, paraplegia)
- Co-morbid medical conditions that may significantly impair physical functional status (e.g., current non-skin malignancies, solid organ transplant in the past year)
- Illicit drug use (other than cannabis). Unreported opioid use would be exclusionary but reported prescribed opioid use is allowed (e.g. patient denies opioid use but is found to be positive on the urine drug screen)
- Self-reported use of cannabis products within the 7 days prior to starting study drug
Show all 28Show fewer
- Self-reported use of cannabis products within the 8-30 days prior to starting study drug AND either a failed drug screen or inability to confirm successful washout (Note - may be rescreened with appropriate wash-out period)
- High daily preoperative opioid dose
- Individuals with major neurological disorders, such as dementia, Parkinson's disease, cognitive impairment, epilepsy, history of traumatic brain injury/head injury, and seizures
- Individuals with significant illness (e.g., cancer) and/or clinically significant labs (e.g. labs measured by complete blood count (CBC) and basic chemistry with values meaningfully outside of the normal range [abnormal levels to be reviewed by the Principal Investigator or prescribing provider])
- Medical or psychiatric conditions that in the judgment of study personnel would preclude participation in this study (e.g., psychosis, suicidal ideation; note that stable anxiety and depression are not exclusions)
- Pregnant or nursing women (total joint arthroplasty is typically not indicated in this group of patients)
- Self-reported liver cirrhosis
- Self-reported uncontrolled diabetes
- Self-reported active hepatitis (any etiology, including infectious, autoimmune, or alcohol-related)
- Blood pressure at screening above 180 millimeters of mercury (mmHg) systolic and/or 120 mmHg diastolic; if value exceeds the set point, potential participants will have repeat assessment within 5 minutes for up to two additional measurements.
- Resting heart rate at screening less than 50 beats per minute (bpm) or greater than 100 bpm; if value exceeds the set point, potential participants will have repeat assessment within 5 minutes for up to two additional measurements.
- Elevated liver enzymes and bilirubin (measured by blood test at screening)
- Serum total bilirubin ≥ 2.5 milligrams (mg) per deciliter (dL) (mg/dL); or,
- Alanine transaminase (ALT) or Alanine transaminase (AST) ≥ 3x upper limit normal (ULN); or,
- Alkaline phosphatase ≥ 2x ULN
- Severe cardiovascular disease (e.g., current unstable angina, current congestive heart failure, or current severe valvular abnormalities) that is self-reported by patient or in medical record
- Current valproate, clobazam, or warfarin use per self-report or medical records
- Current use of strong inducers of cytochrome p450 (CYP) enzymes CYP3A4 and CYP2C19, or CYP2C19 substrates with a narrow therapeutic index
- Self-reported allergies to sesame oil, strawberries, opioids, or cannabis/cannabinoids and confirmed by the investigator during screening
- Any impairment, activity, behavior, or situation that in the judgment of the study team would prevent satisfactory completion of the study protocol
- Self-reported severe side effects to opioids precluding the use of opioids for post-surgical pain and/or clear plan not to use any opioids after surgery and confirmed by the investigator during screening
- Participation in other clinical trials over the course of this study (note: outside of active period is permissible as determined by the investigator during screening)
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Kendall Dubois, 734-232-0324, kendalld@med.umich.edu
Chad Brummet, MD
- Not yet recruiting
Henry Ford Health System
Detroit, Michigan, 48202
Katherine Nowak, 313-771-7128
Lara Zador, MD, lzador1@hfhs.org
About this study
Official title: Cannabidiol for Postoperative Opioid Reduction in Primary Total Knee Arthroplasty - a Randomized, Two by Two Factorial, Double-blind, Placebo-controlled Clinical Trial
The goal of this study is to better understand how daily treatment with cannabidiol (CBD) affects the need for opioid pain medication, as well as pain, inflammation and other related symptoms, after knee replacement surgery. The information collected in this study is necessary to help understand whether CBD may be a useful medication before and/or after surgery.
The study hypothesis is that CBD exerts opioid-sparing effects through anti-inflammatory, analgesic, and anxiolytic mechanisms.
- Conditions
- Knee Replacement Surgery, Osteoarthritis, Knee
- Being tested
- Epidiolex oral solution, Placebo
- Keywords
- Epidiolex, Pain medication
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epidiolex oral solutionDrug
Also called Cannabidiol
Participants assigned to CBD will take the medication one hour before or two hours after eating a meal.
If participants can't tolerate the full-strength dose, the participant can decrease the dosing to 0.75 milliliter twice a day. If this is still not well tolerated, dosing can further be decreased to 0.75 milliliter once per day in the evening.
PlaceboOther
Participants will be instructed to take one hour before or two hours after eating a meal.
| Study group | Role | What they receive |
|---|---|---|
| Pre - and post-operative CBD | Experimental | Participants will take 300 milligrams (mg)/day on days 1-36 (150mg twice a day [b.i.d.]) Receives: Drug: Epidiolex oral solution |
| Pre-operative placebo plus post-operative CBD | Experimental | Participants will take placebo prior to surgery days 1-7, then days 8-36 participants will take CBD 300 milligrams (150mg twice a day [b.i.d.]) Receives: Drug: Epidiolex oral solution; Other: Placebo |
| Pre-operative CBD plus post-operative placebo | Experimental | Participants will take CBD 300 milligrams (mg) /day prior to surgery on days 1-7 (150mg twice a day [b.i.d.]), then days 8-36 will take placebo twice a day [b.i.d.] Receives: Drug: Epidiolex oral solution; Other: Placebo |
| Pre- and post-operative placebo | Placebo comparator | Participants will take placebo on days 1-36 twice a day [b.i.d.] Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total postoperative opioid consumption (measured in oral morphine equivalents) during the 28 days after surgery
Measured: 28 days (after surgery)
Secondary outcomes (15)
The number of treatment-emergent adverse events (TEAEs)
Measured: Five weeks of study treatment (Days 1 - 36)
Proportion of participants with at least one treatment-emergent adverse events (TEAEs)
Measured: Five weeks of study treatment (Days 1 - 36)
The Number of serious adverse events (SAEs)
Measured: Five weeks of study treatment (Days 1 - 36)
Proportion of participants with at least one serious adverse event (SAE)
Measured: Five weeks of study treatment (Days 1 - 36)
Number of deaths due to any cause
Measured: Five weeks of study treatment (Days 1 - 36)
Frequency of deaths due to any cause
Measured: Five weeks of study treatment (Days 1 - 36)
Proportion of participants that prematurely discontinue study medications because of TEAE
Measured: Five weeks of study treatment (Days 1 - 36)
Percentage of participants that meet or exceed the thresholds of liver enzymes
Protocol eligibility exclusion includes:
- Serum total bilirubin ≥ 2.5 milligrams (mg) per deciliter (dL) (mg/dL)
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3x upper limit normal (ULN)
- Alkaline phosphatase ≥ 2x ULN
Measured: Five weeks of study treatment (Days 1 - 36)
Total postoperative opioid consumption (measured in oral morphine equivalents (OME)) during the 28 days after surgery and the pre-operative phase
This is the same outcome as the primary outcome but this secondary endpoint will address the effect of pre-operatively administered CBD and Placebo.
Measured: 36 days (pre-post operative)
Worst pain intensity for surgical site between groups during 7-day epochs from day of surgery through end of active intervention
This is a scale from 0-10 (numerical rating scale, 10 worse pain) in which the participants rate the worse pain.
Measured: Days 8-36 (post-surgery)
Anxiety based on the Patient-Reported Outcomes Measurement Information System (PROMIS)-29+2 profile v2.1
There are 4-questions on this survey regarding anxiety. Participants answer the questions from never (1) to always (5). Scores range from 4-20 with a higher score indicating higher levels of anxiety.
Measured: pre-op days 1-7
Anxiety based on the Patient-Reported Outcomes Measurement Information System (PROMIS)-29+2 profile v2.1
There are 4-questions on this survey regarding anxiety. Participants answer the questions from never (1) to always (5). Scores range from 4-20 with a higher score indicating higher levels of anxiety.
Measured: post-op days 8-36
Sleep disturbance on the PROMIS-29+2 v.2.1
There are 4-questions on this survey regarding sleep disturbance with a likert type scale.
Scores range from 4-20 with a higher score indicating higher levels of sleep disturbance.
Measured: pre-op days 1-7
Sleep disturbance on the PROMIS-29+2 v.2.1
There are 4-questions on this survey regarding sleep disturbance with a likert type scale.
Scores range from 4-20 with a higher score indicating higher levels of sleep disturbance.
Measured: post-op days 8-36
Change in Interleukin-6 (IL-6) levels in the blood (University of michigan site only)
Measured: Baseline, up to day 36 (post -surgery)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2024
- Study start13 Mar 2024
- Primary completionJan 2029 (estimated)
- Study completionJan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Knee Replacement SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- Participants will be randomized once before surgery and once the day of surgery.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 380 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chad Brummett
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Sponsor-investigator, Chad Brummett, University of Michigan
- Investigators
- Chad Brummett, MD, Principal investigator, University of MichiganKevin F Boehnke, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06234631
- Sponsor's protocol ID
- HUM00239715
- Other IDs
- 1U01AR083132-01
- Acronym
- CORK
- Status last verified
- Apr 2026
- First submitted
- 22 Jan 2024
- Last updated
- 15 Apr 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The final de-identified, anonymized dataset or the minimum necessary will be available upon request or from a University of Michigan repository. The final dataset will include demographics, perioperative medical record data, patient-reported outcomes, daily pain and medication diary data, functional testing scores, and biomarkers of inflammation and pharmacokinetics. The study team anticipates 1 data file with baseline, day of surgery, 2 week, 1-month, 3-month, and 6-month follow-up data.
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cannabidiol for Postoperative Opioid Reduction in Primary Total Knee Arthroplasty - a Randomized, Two by Two Factorial, Double-blind, Placebo-controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT06234631
- Acronym / sponsor ID
- CORK / HUM00239715
- Conditions
- Knee Replacement Surgery, Osteoarthritis, Knee
- Keywords
- Epidiolex, Pain medication
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 380 participants (estimated)
- Lead sponsor
- Chad BrummettUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- 13 Mar 2024 (actual)
- Primary completion
- Jan 2029 (estimated)
- Study completion
- Jan 2029 (estimated)
- First posted
- 31 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to better understand how daily treatment with cannabidiol (CBD) affects the need for opioid pain medication, as well as pain, inflammation and other related symptoms, after knee replacement surgery. The information collected in this study is necessary to help understand whether CBD may be a useful medication before and/or after surgery.
The study hypothesis is that CBD exerts opioid-sparing effects through anti-inflammatory, analgesic, and anxiolytic mechanisms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- Model description
- Participants will be randomized once before surgery and once the day of surgery.
| Arm | Type | Receives |
|---|---|---|
| Pre - and post-operative CBD | Experimental | Drug: Epidiolex oral solutionParticipants will take 300 milligrams (mg)/day on days 1-36 (150mg twice a day [b.i.d.]) |
| Pre-operative placebo plus post-operative CBD | Experimental | Drug: Epidiolex oral solution, Other: PlaceboParticipants will take placebo prior to surgery days 1-7, then days 8-36 participants will take CBD 300 milligrams (150mg twice a day [b.i.d.]) |
| Pre-operative CBD plus post-operative placebo | Experimental | Drug: Epidiolex oral solution, Other: PlaceboParticipants will take CBD 300 milligrams (mg) /day prior to surgery on days 1-7 (150mg twice a day [b.i.d.]), then days 8-36 will take placebo twice a day [b.i.d.] |
| Pre- and post-operative placebo | Placebo comparator | Other: PlaceboParticipants will take placebo on days 1-36 twice a day [b.i.d.] |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Willing and able to read, understand, and sign the informed consent (English)
- Willingness to participate in all study measures and restrictions, including patient-reported outcomes and longitudinal follow-up
- Scheduled for surgery: primary total knee arthroplasty
- Primary diagnosis of osteoarthritis of the surgical knee
- Individuals of reproductive potential must agree to use acceptable birth control (defined in manual of operating procedures). This includes currently practicing an effective form of two types of birth control for women of childbearing potential, which are defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly from the screening visit until 28 days after the last study drug administration.
Key exclusion criteria (28 listed)
- Revision or bilateral total knee arthroplasty
- Individuals receiving or actively applying for worker's compensation or disability and other aspects associated with potential secondary gain (postoperative disability for recovery is permitted)
- Severe physical impairment or clinically significant illness (e.g., blindness, paraplegia)
- Co-morbid medical conditions that may significantly impair physical functional status (e.g., current non-skin malignancies, solid organ transplant in the past year)
- Illicit drug use (other than cannabis). Unreported opioid use would be exclusionary but reported prescribed opioid use is allowed (e.g. patient denies opioid use but is found to be positive on the urine drug screen)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Epidiolex oral solutionAlso: CannabidiolParticipants assigned to CBD will take the medication one hour before or two hours after eating a meal. If participants can't tolerate the full-strength dose, the participant can decrease the dosing to 0.75 milliliter twice a day. If this is still not well tolerated, dosing can further be decreased to 0.75 milliliter once per day in the evening. | Drug | Pre - and post-operative CBD, Pre-operative CBD plus post-operative placebo, Pre-operative placebo plus post-operative CBD |
| PlaceboParticipants will be instructed to take one hour before or two hours after eating a meal. | Other | Pre- and post-operative placebo, Pre-operative CBD plus post-operative placebo, Pre-operative placebo plus post-operative CBD |
Primary outcome
Total postoperative opioid consumption (measured in oral morphine equivalents) during the 28 days after surgery
Time frame: 28 days (after surgery)
15 secondary outcomes
The number of treatment-emergent adverse events (TEAEs)
Time frame: Five weeks of study treatment (Days 1 - 36)
Proportion of participants with at least one treatment-emergent adverse events (TEAEs)
Time frame: Five weeks of study treatment (Days 1 - 36)
The Number of serious adverse events (SAEs)
Time frame: Five weeks of study treatment (Days 1 - 36)
Proportion of participants with at least one serious adverse event (SAE)
Time frame: Five weeks of study treatment (Days 1 - 36)
Number of deaths due to any cause
Time frame: Five weeks of study treatment (Days 1 - 36)
Frequency of deaths due to any cause
Time frame: Five weeks of study treatment (Days 1 - 36)
Proportion of participants that prematurely discontinue study medications because of TEAE
Time frame: Five weeks of study treatment (Days 1 - 36)
Percentage of participants that meet or exceed the thresholds of liver enzymes
Time frame: Five weeks of study treatment (Days 1 - 36)
Total postoperative opioid consumption (measured in oral morphine equivalents (OME)) during the 28 days after surgery and the pre-operative phase
Time frame: 36 days (pre-post operative)
Worst pain intensity for surgical site between groups during 7-day epochs from day of surgery through end of active intervention
Time frame: Days 8-36 (post-surgery)
Anxiety based on the Patient-Reported Outcomes Measurement Information System (PROMIS)-29+2 profile v2.1
Time frame: pre-op days 1-7
Anxiety based on the Patient-Reported Outcomes Measurement Information System (PROMIS)-29+2 profile v2.1
Time frame: post-op days 8-36
Sleep disturbance on the PROMIS-29+2 v.2.1
Time frame: pre-op days 1-7
Sleep disturbance on the PROMIS-29+2 v.2.1
Time frame: post-op days 8-36
Change in Interleukin-6 (IL-6) levels in the blood (University of michigan site only)
Time frame: Baseline, up to day 36 (post -surgery)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2026.
- Individual participant dataSharing planned: Yes. The final de-identified, anonymized dataset or the minimum necessary will be available upon request or from a University of Michigan repository. The final dataset will include demographics, perioperative medical record data, patient-reported outcomes, daily pain and medication diary data, functional testing scores, and biomarkers of inflammation and pharmacokinetics. The study team anticipates 1 data file with baseline, day of surgery, 2 week, 1-month, 3-month, and 6-month follow-up data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Chad Brummett, MD principal investigator
University of Michigan
Kevin F Boehnke principal investigator
University of Michigan
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Epidiolex oral solution in people with Knee Replacement Surgery and Osteoarthritis, Knee, run by Chad Brummett at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kendall Dubois (734-232-0324, kendalld@med.umich.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total postoperative opioid consumption (measured in oral morphine equivalents) during the 28 days after surgery (time frame: 28 days (after surgery)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2026.