Cannabidiol for Pain Management After Knee Replacement

(CORK Trial)

Recruiting at 1 trial location

Overseen By Katherine Nowak

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Chad Brummett

Must not be taking: Valproate, Clobazam, Warfarin, others

Disqualifiers: Illicit drug use, Neurological disorders, Cancer, Uncontrolled diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

380 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how cannabidiol (CBD) might help manage pain and reduce the need for opioid medications after knee replacement surgery. Researchers aim to determine if CBD can ease pain, reduce inflammation, and improve recovery. Participants will receive CBD either before and after surgery, only before, only after, or a placebo (a substance with no therapeutic effect). Suitable candidates for this trial are those scheduled for knee replacement surgery due to osteoarthritis who do not use cannabis products or have high preoperative opioid use. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those using certain drugs like valproate, clobazam, warfarin, and strong inducers of specific liver enzymes. It's best to discuss your current medications with the study team to see if they might affect your eligibility.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that cannabidiol (CBD) is generally safe for people. In a study with 36 patients using CBD after surgery, most did not experience significant side effects. This study examined whether CBD could help reduce pain and the need for opioids and found no major safety issues. Additionally, the FDA has approved CBD for certain uses, indicating its safety when used correctly. Overall, these findings suggest that CBD is relatively safe for managing post-surgical pain, though individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about using cannabidiol (CBD) for pain management after knee replacement because it offers a potential alternative to traditional pain relief methods like opioids and NSAIDs. Unlike these standard treatments, CBD is derived from cannabis and may provide pain relief without the risk of addiction and severe side effects associated with opioids. Additionally, CBD has anti-inflammatory properties, which could aid in reducing swelling and promoting quicker recovery. This trial explores various ways CBD can be used, such as pre-surgery, post-surgery, or throughout the entire recovery period, to determine the most effective approach.

What evidence suggests that cannabidiol could be an effective treatment for pain management after knee replacement?

This trial will evaluate the effectiveness of cannabidiol (CBD) for pain management after knee replacement surgery. Research has shown that CBD might help with pain and swelling without causing a "high." Some studies suggest that CBD can reduce pain, calm anxiety, and decrease inflammation, which could aid in post-surgery pain relief. However, other studies, such as one using CBD cream after knee surgery, did not find significant differences in pain relief or the need for painkillers. Despite these mixed results, more than 80% of patients surveyed believe CBD is effective for managing pain. Many people trust its benefits, even though scientific evidence varies. Participants in this trial will be assigned to different arms, receiving either CBD or a placebo at various stages to assess its impact on post-operative pain. ^{2 4 6 7 8}

Who Is on the Research Team?

Chad Brummett, MD

Principal Investigator

University of Michigan

Kevin F Boehnke

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for adults who have had a knee replacement surgery due to osteoarthritis and are in need of pain management. Participants should not be currently using CBD or cannabis products, must not have allergies to cannabinoids, and should not be on certain medications that could interact with CBD.

Inclusion Criteria

My main diagnosis is knee osteoarthritis.

I am scheduled for a first-time knee replacement surgery.

Willing and able to read, understand, and sign the informed consent (English)

Exclusion Criteria

I have a serious illness or significant lab results.

Medical or psychiatric conditions that in the judgment of study personnel would preclude participation in this study

Any impairment, activity, behavior, or situation that in the judgment of the study team would prevent satisfactory completion of the study protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Treatment

Participants receive either CBD or placebo prior to surgery

1 week

1 visit (in-person)

Post-operative Treatment

Participants receive either CBD or placebo after surgery

5 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol

Trial Overview The study is testing whether taking cannabidiol (CBD) orally can reduce the need for opioid painkillers after knee surgery. Patients will either receive Epidiolex, a CBD solution, or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Pre-operative placebo plus post-operative CBD Experimental Treatment 2 Interventions

Participants will take placebo prior to surgery days 1-7, then days 8-36 participants will take CBD 300 milligrams (150mg twice a day \[b.i.d.\])

Group II: Pre-operative CBD plus post-operative placebo Experimental Treatment 2 Interventions

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 \[b.i.d.\]

Group III: Pre - and post-operative CBD Experimental Treatment 1 Intervention

Participants will take 300 milligrams (mg)/day on days 1-36 (150mg twice a day \[b.i.d.\])

Group IV: Pre- and post-operative placebo Placebo Group 1 Intervention

Participants will take placebo on days 1-36 twice a day \[b.i.d.\]

Cannabidiol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in Canada as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Who Is Running the Clinical Trial?

Chad Brummett

Lead Sponsor

Trials

1

Recruited

380+

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Collaborator

Trials

508

Recruited

1,090,000+

Published Research Related to This Trial

In a study of 109 patients who underwent total hip or knee replacement surgeries, 22% reported using cannabidiol (CBD) during their treatment period.

Despite the prevalence of CBD use, there was no significant difference in pain satisfaction between those who used CBD and those who did not, indicating a need for further research on the safety and efficacy of CBD in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rates of self-directed perioperative cannabidiol use in patients undergoing total hip or knee arthroplasty. Yu, JS., Premkumar, A., Liu, S., et al.[2021]

In a study of 160 patients undergoing total knee arthroplasty, the transdermal buprenorphine (TDB) patch provided significantly better pain relief compared to oral celecoxib, as indicated by lower visual analogue scale (VAS) scores during rest and activity at multiple time points post-surgery.

Patients using the TDB patch required less morphine for pain management and showed improved functional recovery, with greater range of motion and higher Lysholm scores, all without an increase in adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal buprenorphine patch versus oral celecoxib for pain management after total knee arthroplasty: An open- label, randomized controlled trial. Xu, X., Xie, L., Liu, H., et al.[2021]

In a pilot study, patients who received local infiltration analgesia combined with anti-hyperalgesic drugs (pregabalin and s-ketamine) achieved an average knee flexion of 88.5 degrees by the second postoperative day, indicating effective pain management and improved mobility after total knee arthroplasty.

The side effects of this drug combination were mild and mostly self-limiting, suggesting that the method is safe for patients in the early postoperative period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of addition of pregabalin and s-ketamine to local infiltration analgesia on the knee function outcome after total knee arthroplasty. Kadic, L., Niesten, E., Heijnen, I., et al.[2015]

Intra-articular administration of 10 mg of morphine after total knee arthroplasty significantly reduced pain severity in the first 6 hours post-surgery compared to a control group receiving saline.

Patients receiving morphine also experienced a longer time before needing additional pain relief and consumed less analgesics in the first 24 hours, with no increase in side effects compared to the control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic efficacy of the intra-articular administration of high doses of morphine in patients undergoing total knee arthroplasty. Garcia, JB., Barbosa Neto, JO., Vasconcelos, JW., et al.[2019]

In a study involving 80 patients who underwent total knee arthroplasty, topical CBD did not provide additional pain relief or reduce opioid consumption compared to a placebo, indicating it may not be effective for postoperative pain management.

The CBD group actually reported higher pain scores on postoperative day 2 compared to the essential oil group, suggesting that topical CBD may not be beneficial in the context of multimodal analgesia following surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Cannabidiol (CBD) After Total Knee Arthroplasty Does Not Decrease Pain or Opioid Use: A Prospective Randomized Double-Blinded Placebo-Controlled Trial. Haffar, A., Khan, IA., Abdelaal, MS., et al.[2022]

Oral dexamethasone significantly reduced postoperative pain scores in patients undergoing total knee arthroplasty, particularly on postoperative days 2, 3, and 4, compared to a placebo group.

Despite the pain reduction, there were no significant differences in opioid usage, nausea, vomiting, or other complications between the dexamethasone and placebo groups, suggesting a favorable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The AAHKS Clinical Research Award: Oral Dexamethasone Following Total Knee Arthroplasty: A Double-Blind, Randomized Controlled Trial. Shaw, JH., Wesemann, LD., Banka, TR., et al.[2023]

Applying a buprenorphine transdermal patch directly to the knee of osteoarthritis patients resulted in a significant reduction in pain, as measured by the Numeric Rating Scale (NRS), compared to applying the patch on the chest.

The knee application method also had fewer adverse effects (19.32% vs. 64.00% for chest application) and higher patient compliance (82.95% vs. 37.60%), suggesting it is a safer and more effective option for managing knee OA pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Application of Buprenorphine Transdermal Patch to Relieve Pain in the Knee Joint of Knee Osteoarthritis Patients: A Retrospective Case-Control Study. Gil, HY., Park, S., Kim, NE., et al.[2020]

Cannabidiol (CBD) has shown potential therapeutic effects for pain and inflammation, but the evidence is inconclusive due to variations in study methods, including different routes of administration and types of pain assessed, with most studies involving small participant numbers.

Positive results were consistently observed in studies focusing on the effects of CBD on arthritis, suggesting it may be particularly beneficial for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Cannabidiol in Inflammation: A Review of Pre-clinical and Clinical Findings. Sklenárová, M., Šíma, M., Slanař, O.[2023]

In a study of 150 patients undergoing arthroscopic ACL reconstruction, intra-articular injection of 5 mg morphine significantly reduced postoperative pain compared to a placebo, leading to lower analgesic requirements in the first 12 hours after surgery.

Morphine was found to be the most effective pain reliever among the opioids tested, while methadone showed the least response, suggesting that morphine is a valuable addition to local anesthetics for pain management in knee surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The comparison effects of intra-articular injection of different opioids on postoperative pain relieve after arthroscopic anterior cruciate ligament reconstruction: A randomized clinical trial study. Arti, H., Mehdinasab, SA.[2022]

In a study of 60 patients undergoing total knee arthroplasty, both pregabalin and duloxetine significantly reduced pain and the need for additional pain relief within the first 48 hours after surgery compared to a placebo.

However, neither medication had a significant impact on long-term knee mobility, as measured by the WOMAC score six months post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Perioperative Pregabalin and Duloxetine for Pain Management After Total Knee Arthroplasty: A Double-Blind Clinical Trial. Imani, F., Emami, A., Alimian, M., et al.[2023]

In a study of 45 patients undergoing bilateral total knee arthroplasty, the addition of steroids to local infiltration analgesia significantly reduced pain levels and improved rehabilitation outcomes compared to LIA without steroids, particularly in the first week post-surgery.

Steroid-treated knees showed better range of motion and quicker recovery of active straight leg raises, with no increase in complications or adverse effects observed over a 1-year follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Steroid in Local Infiltration Analgesia in One-Stage Bilateral Total Knee Arthroplasty: A Paired-Randomized Controlled Study. Chan, VWK., Chan, PK., Yan, CH., et al.[2022]

In a study of 195 patients undergoing total hip and knee arthroplasty, 16.4% reported using CBD/THC products during the perioperative period, with higher usage in knee arthroplasty patients (22.6%) compared to hip arthroplasty patients (11.7%).

Despite the use of CBD/THC products, there was no significant difference in opioid consumption, pain scores, or length of hospital stay between users and non-users, suggesting that these products may not significantly impact post-operative opioid requirements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Tetrahydrocannabinol and Cannabidiol Products in the Perioperative Period Around Primary Unilateral Total Hip and Knee Arthroplasty. Runner, RP., Luu, AN., Nassif, NA., et al.[2021]

In a randomized, double-blind, placebo-controlled trial involving 136 patients with hand osteoarthritis or psoriatic arthritis, cannabidiol (CBD) did not show a significant reduction in pain intensity compared to placebo after 12 weeks of treatment.

The study found no meaningful effects of CBD on secondary outcomes such as sleep quality, anxiety, or depression, indicating that CBD may not be an effective add-on therapy for pain management in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol treatment in hand osteoarthritis and psoriatic arthritis: a randomized, double-blind, placebo-controlled trial. Vela, J., Dreyer, L., Petersen, KK., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0883540322003837

Topical Cannabidiol (CBD) After Total Knee Arthroplasty ... Utilization of topical CBD in supplement to multimodal analgesia did not reduce pain or opioid consumption, or improve sleep scores following TKA.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11968025/

Cannabidiol Perceptions and Use in the Orthopaedic ... Over 80% of the surveyed patients agreed that CBD might be effective for pain management (p < 0.05). ... efficacy in the management of joint ...

3. trialx.com trialx.com/clinical-trials/listings/246651/cannabinoids-vs-placebo-on-persistent-post-surgical-pain-following-tka-a-pilot-rct/

Cannabinoids vs. Placebo on Persistent Post-surgical Pain ... Studies of CBD have shown analgesic, anti-inflammatory, and anti-anxiety properties, but without the psychoactive effects (feeling 'high') that ...

4. academic.oup.com academic.oup.com/painmedicine/advance-article/doi/10.1093/pm/pnaf110/8238175

Cannabis and cannabidiol for postoperative pain ... Preclinical studies have also shown enhanced bone healing and reduced proinflammatory cytokine release with CBD administration, though data in the human ...

5. withpower.com withpower.com/trial/phase-2-total-knee-replacement-surgery-1-2024-ed78b

Cannabidiol for Pain Management After Knee Replacement In a study involving 80 patients who underwent total knee arthroplasty, topical CBD did not provide additional pain relief or reduce opioid consumption compared ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04749628?term=CBD&cond=bilateral%20knee&rank=1

Cannabidiol for Bilateral Total Knee Arthroplasty 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 ...

7. news.hss.edu news.hss.edu/hss-pilot-study-announced-at-esra-annual-meeting-examines-the-role-of-cannabidiol-in-total-knee-arthroplasty-pain-management/

HSS Pilot Study Announced at ESRA Annual Meeting ... The pilot study, conducted over four years, followed 36 patients who received cannabidiol as a part of their treatment following surgery.

8. trialx.com trialx.com/clinical-trials/listings/302119/cannabidiol-for-postoperative-opioid-reduction-in-primary-total-knee-arthroplasty/

Cannabidiol for Postoperative Opioid Reduction in Primary ... The goal of this study is to better understand how daily treatment with cannabidiol (CBD) affects the need for opioid pain medication, as well ...