Cannabidiol for Postoperative Opioid Reduction in Primary Total Knee Arthroplasty

NCT06234631 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: HUM002397151U01AR083132-01
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 2

Brief 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. 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

Keywords

Epidiolex; Pain medication

Outcome Measures

Primary Outcomes (1)

• Total postoperative opioid consumption (measured in oral morphine equivalents) during the 28 days after surgery

  28 days (after surgery)

Secondary Outcomes (15)

• The number of treatment-emergent adverse events (TEAEs)

  Five weeks of study treatment (Days 1 - 36)

• Proportion of participants with at least one treatment-emergent adverse events (TEAEs)

  Five weeks of study treatment (Days 1 - 36)

• The Number of serious adverse events (SAEs)

  Five weeks of study treatment (Days 1 - 36)

• Proportion of participants with at least one serious adverse event (SAE)

  Five weeks of study treatment (Days 1 - 36)

• Number of deaths due to any cause

  Five weeks of study treatment (Days 1 - 36)

Study Arms (4)

Pre - and post-operative CBD

EXPERIMENTAL

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

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 \[b.i.d.\])

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 \[b.i.d.\]

Drug: Epidiolex oral solution; Other: Placebo

Pre- and post-operative placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Epidiolex oral solution DRUG

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.

Also known as: Cannabidiol

Pre - and post-operative CBD; Pre-operative CBD plus post-operative placebo; Pre-operative placebo plus post-operative CBD

Placebo OTHER

Participants will be instructed to take one hour before or two hours after eating a meal.

Pre- and post-operative placebo; Pre-operative CBD plus post-operative placebo; Pre-operative placebo plus post-operative CBD

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• Self-reported use of cannabis products within the 7 days prior to starting study drug
• 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 \[abnormal levels to be reviewed by the Principal Investigator or prescribing provider\])
• 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.

Sponsors & Collaborators

• Chad Brummett: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (2)

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Henry Ford Health System

Detroit, Michigan, 48202, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Chad Brummett, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Kevin F Boehnke

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kendall Dubois

CONTACT

734-232-0324; kendalld@med.umich.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The participants and the study team at each site will be blinded except for the site research pharmacist and the site project manager (PM) and/or PM delegate.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Anesthesiology Research, Associate Chair for Research

Model Details: Participants will be randomized once before surgery and once the day of surgery.

Study Record Dates

• First Submitted: January 22, 2024
• First Posted: January 31, 2024
• Study Start: March 13, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be made available by request 5 years after the completion of the primary endpoint.
• Access Criteria: Access may be requested by contacting PI, Dr. Chad Brummett at cbrummet@umich.edu or the University of Michigan repository. A data use agreement may also be required.

Locations

US (2)