Cannabidiol for Pain Management After Knee Replacement (CORK Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Chad Brummett
Prior Safety Data
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this 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.
Is cannabidiol (CBD) safe for use in humans?
Research shows that cannabidiol (CBD) is generally safe for human use, with studies indicating no significant difference in adverse events between CBD and placebo groups. However, more research is needed to fully understand its safety profile, especially in the context of pain management after knee replacement.
5891013How does the drug Cannabidiol (CBD) differ from other treatments for pain management after knee replacement?
Cannabidiol (CBD) is unique because it is a non-psychoactive compound derived from cannabis, and it is being explored for its potential to manage pain without the side effects associated with opioids. Unlike traditional pain medications like opioids or NSAIDs, CBD is thought to work by interacting with the body's endocannabinoid system, which may help reduce inflammation and pain.
2361012Will 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.
What data supports the effectiveness of the drug Cannabidiol (CBD) for pain management after knee replacement?
The study titled 'Topical Cannabidiol (CBD) After Total Knee Arthroplasty Does Not Decrease Pain or Opioid Use' found that CBD did not provide pain relief or reduce opioid use after knee replacement surgery.
1471011Eligibility Criteria
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.
Exclusion Criteria
I have a severe physical condition like blindness or paralysis.
I take a high dose of painkillers daily before surgery.
I am not taking medication that strongly affects certain liver enzymes.
I cannot use opioids for pain due to severe side effects or have decided not to use them after surgery.
I am having or have had a knee replacement on both knees or a redo.
I am currently taking valproate, clobazam, or warfarin.
I have been diagnosed with liver cirrhosis.
I have diabetes that is not well-controlled.
I have active hepatitis.
I do not have severe heart problems like unstable chest pain or heart failure.
Participant Groups
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.
4Treatment groups
Experimental Treatment
Placebo Group
Group I: Pre-operative placebo plus post-operative CBDExperimental Treatment2 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 placeboExperimental Treatment2 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 CBDExperimental Treatment1 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 placeboPlacebo Group1 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
University of MichiganAnn Arbor, MI
Henry Ford Health SystemDetroit, MI
Loading ...
Who is running the clinical trial?
Chad BrummettLead Sponsor
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)Collaborator
References
Analgesic efficacy of the intra-articular administration of high doses of morphine in patients undergoing total knee arthroplasty. [2019]Although the efficacy of intraarticular (IA) morphine is still controversial, it has been shown that higher doses promote better results and consequently decrease postoperative analgesic consumption, characterizing a dose-dependent peripheral action. A controlled, randomized, double-blind study was undertaken to evaluate the efficacy of the intra-articular administration of 10 mg of morphine in patients undergoing total knee arthroplasty.
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. [2022]Pain after knee surgery, if not relieved, it would lead to a more severe and prolonged pain that can delay the patients recovery and rehabilitation. The effect of pain relief by some drugs after intra-articular injection has been shown. This study compared the effect of intra-articular injection of opioids (morphine, pethidine, methadone, and tramadol) on postoperative relieving pain after arthroscopic anterior cruciate ligament (ACL) reconstruction.
The effect of addition of pregabalin and s-ketamine to local infiltration analgesia on the knee function outcome after total knee arthroplasty. [2015]Pain reduction is important for early mobilization after total knee arthroplasy. Recent studies show that local infiltration analgesia and addition of anti-hyperalgesic drugs (pregabalin and s-ketamine) may improve postoperative analgesia and mobilization. This pilot study was meant to evaluate if this new method of analgesia might improve patients' ability to exercise in the first postoperative days. The secondary goal was to determine what side effects could be expected by using this drug combination. A pilot study showed that patients achieved knee flexion of 88.5 degrees (SD 9.6) already on the second postoperative day. The side effects were mild and mostly self-limiting.
A Novel Application of Buprenorphine Transdermal Patch to Relieve Pain in the Knee Joint of Knee Osteoarthritis Patients: A Retrospective Case-Control Study. [2020]Osteoarthritis (OA) is considered to be one of the most disabling diseases. The intra-articular opioid injection has been widely studied for its simplicity, safety, and efficacy in OA. In this study, however, we suggest a novel method of buprenorphine transdermal patch (BTDP) to painful knee joints of OA patients, instead of intra-articular opioid injection, and subsequently compared the knee application with conventional chest application. We retrospectively enrolled 213 patients with knee OA who did not respond to conventional therapy. The Numeric Rating Scale (NRS), adverse effects, and compliance were recorded before and after the application of the BTDP. All parameters were compared between the knee applied group and the chest applied group. After the BTDP application, the NRS score in the knee applied group was lower than that of the chest applied group (p = 0.007). NRS scores after buprenorphine patch decreased to 2.21 ± 0.77, and 2.55 ± 0.71 in the chest applied group and the knee applied group, respectively. The adverse effects were 19.32% in the knee applied group, and 64.00% in the chest applied group. The compliances were 82.95% and 37.60% in the knee applied group and chest applied group, respectively. This novel application of BTDP directly to the painful knee joint of knee OA patients led to a decrease in the NRS score, adverse effects, and an increase in compliance compared with the chest application method.
Use of Tetrahydrocannabinol and Cannabidiol Products in the Perioperative Period Around Primary Unilateral Total Hip and Knee Arthroplasty. [2021]Given the opioid crisis in America, patients are trying alternative medications including tetrahydrocannabinol (THC) and other cannabidiol (CBD) containing products in the perioperative period, especially in states where these products are legal. This study sought to analyze usage rates of CBD/THC products in the perioperative period for primary unilateral total hip and knee arthroplasty (THA/TKA) patients and identify a possible association with post-operative opioid use.
Transdermal buprenorphine patch versus oral celecoxib for pain management after total knee arthroplasty: An open- label, randomized controlled trial. [2021]This study was performed to evaluate the analgesic efficacy and safety of transdermal buprenorphine (TDB) patched for post-operative pain control after total knee arthroplasty (TKA). The hypothesis was that patients receiving the TDB patch would have less pain in comparison to those treated with the oral COX-2 inhibitor celecoxib without increasing side effects.
Effect of Steroid in Local Infiltration Analgesia in One-Stage Bilateral Total Knee Arthroplasty: A Paired-Randomized Controlled Study. [2022]Although local infiltration analgesia (LIA) is effective in relieving pain after total knee arthroplasty (TKA), its effect is short lasting and the optimal combination of drugs is unknown. Steroids being a potent and long-acting anti-inflammatory drug might extend LIA's effect. This study aims to evaluate the role of steroids in LIA. This is a paired-randomized controlled study involving one-stage bilateral TKA patients. LIA containing ropivacaine, ketorolac, and adrenaline with or without triamcinolone was given. One knee was randomized to receive LIA with steroids, while the other received LIA without steroids. The primary outcome was knee pain in terms of the visual analog scale (VAS). Secondary outcomes were rehabilitation progress, functional scores, and complications. Outcomes were compared between the knees of the same patient and documented up to 1 year. A total of 45 patients (90 TKAs) were included. LIA with steroid knees showed lower VAS score at rest and during activity from postoperation day 1 to 5 and at 6 weeks (p < 0.05). Passive and active range of movement was also greater in LIA with steroid group from day 1 to 7 and day 2 to 5, respectively (p < 0.05). Steroid-treated knees also achieved active straight leg raise earlier (1.2 vs. 2.0 days, p < 0.05). No differences in Knee Society Score and complication rates between both groups. Steroids in LIA offer additional and extended benefit in pain control and rehabilitation after TKA, while no adverse effects were found up to 1-year follow-up.
Rates of self-directed perioperative cannabidiol use in patients undergoing total hip or knee arthroplasty. [2021]Aim: To evaluate the prevalence of self-directed cannabidiol (CBD) use in patients with end-stage degenerative hip and knee arthritis who underwent total hip arthroplasty and total knee arthroplasty. Materials & methods: Anonymous surveys for 109 patients were completed at 6 weeks follow-up after either total hip arthroplasty or total knee arthroplasty at a single tertiary care US orthopedic hospital. Results: Within the perioperative window encompassing both preoperative and postoperative periods, 22% (95% CI: 14-30%) of patients used CBD. Conclusion: There was no difference in pain satisfaction between patients who used CBD and patients who did not. Given high rates of self-directed perioperative CBD use and the mixed body of evidence, further research is needed to better understand whether CBD is safe and effective.
Cannabidiol treatment in hand osteoarthritis and psoriatic arthritis: a randomized, double-blind, placebo-controlled trial. [2022]Cannabidiol (CBD) is increasingly used as analgesic medication although the recent International Association for the Study of Pain Presidential Task Force on cannabis and cannabinoid analgesia found a lack of trials examining CBD for pain management. This trial examines CBD as add-on analgesic therapy in patients with hand osteoarthritis or psoriatic arthritis experiencing moderate pain intensity despite therapy. Using a randomized, double-blind, placebo-controlled design, patients received synthetic CBD 20 to 30 mg or placebo daily for 12 weeks. The primary outcome was pain intensity during the past 24 hours (0-100 mm); safety outcomes were percentage of patients experiencing adverse events and a characterization of serious adverse events. Explorative outcomes included change in Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale (PCS), and Health Assessment Questionnaire Disability Index. One hundred thirty-six patients were randomized, of which 129 were included in the primary analysis. Between-group difference in pain intensity at 12 weeks was 0.23 mm (95% confidence interval -9.41 to 9.90; P = 0.96). Twenty-two percent patients receiving CBD and 21% receiving placebo experienced a reduction in pain intensity of more than 30 mm. We found neither clinically nor statistically significant effects of CBD for pain intensity in patients with hand osteoarthritis and psoriatic arthritis when compared with placebo. In addition, no statistically significant effects were found on sleep quality, depression, anxiety, or pain catastrophizing scores.
Topical Cannabidiol (CBD) After Total Knee Arthroplasty Does Not Decrease Pain or Opioid Use: A Prospective Randomized Double-Blinded Placebo-Controlled Trial. [2022]Multimodal analgesia has become the standard of care for pain management following total knee arthroplasty (TKA). Cannabidiol (CBD) is increasingly utilized in the postoperative period. The purpose of this study was to analyze the analgesic benefits of topical CBD following primary TKA.
The AAHKS Clinical Research Award: Oral Dexamethasone Following Total Knee Arthroplasty: A Double-Blind, Randomized Controlled Trial. [2023]Intravenous dexamethasone has been shown to reduce pain in total joint arthroplasty. This double-blind, randomized, placebo-controlled trial investigated the postoperative effects and safety of oral dexamethasone as a potential augment to multimodal pain management in outpatient knee arthroplasty.
Comparison of Perioperative Pregabalin and Duloxetine for Pain Management After Total Knee Arthroplasty: A Double-Blind Clinical Trial. [2023]Chronic residual pain after total knee arthroplasty (TKA) is one of the challenges of postoperative pain management. Duloxetine, by controlling neuropathic pain, and pregabalin, by affecting nociceptors, can effectively manage postoperative pain.
Effects of Cannabidiol in Inflammation: A Review of Pre-clinical and Clinical Findings. [2023]Cannabidiol (CBD) is the second most abundant component of the plant Cannabis sativa. Currently, CBD is approved for Lennox-Gastaut and Dravet syndrome and newly for tuberous sclerosis complex. However, based on the available data, CBD migth have a broad spectrum of potential therapeutic uses. Therefore, the aim of this review was to summarize the evidence on the effects of CBD on pain and inflammation of various causes. PubMed and Web of Science databases were searched until January 2023. The medical keyword term "cannabidiol" was combined with "pain", "arthritis", and "inflammation". Based on the initial search for these terms, 9, 5, and 5 relevant publications have been selected. Based on the available data, it is not possible to draw a clear conclusion about the effect of CBD to releave pain, because each study used a different route of administration or treatment regimen. The studies also differed in etiopathogenesis of pain (chronic, neuropathic, and possibly inflammatory pain), and in general included only small number of subjects. In case of anti-inflammatory qualities of CBD, its effect on the intestinal system is negligible. On the other hand, positive treatment results were observed in all publications dealing with the effect of CBD on arthritis.