Cannabidiol (CBD) in Pain Reduction for Knee Osteoarthritis

• ClinicalTrials.gov Identifier: NCT05020028
• Recruitment Status: Recruiting
• First Posted: August 25, 2021
• Last Update Posted: May 24, 2023
• Sponsor: NYU Langone Health
• Collaborator: Orcosa Inc.
• Information provided by (Responsible Party): NYU Langone Health

Study Description

Brief Summary:

The purpose of this study is to see if cannabidiol (CBD) orally dissolving tablets (ODTs) can lessen pain, improve function, and improve patient satisfaction in cases of knee osteoarthritis. CBD comes from the cannabis plant and is non-psychoactive (i.e. does not produce a 'high' or altered mental state) as compared to tetrahydrocannabinol (THC), another compound found in cannabis. Researchers are studying different forms of CBD for potential use in treating pain, inflammation, and illnesses.

Condition or disease	Intervention/treatment	Phase
Knee Arthritis	Drug: Cannabidiol (CBD); Drug: Placebo	Phase 2; Phase 3

Detailed Description:

This will be a multi-center, double-blinded, randomized, placebo-controlled study. The study is comparing pain, outcomes, and patient satisfaction in two cohorts: patients with knee OA undergoing physiotherapy/home exercises who receive CBD and a placebo group with PT/home exercise program. Patients will be asked on treatment Day 1, 2, 7, and 14, 28, 42, and 84 to rate their pain according to the VAS scale. Additionally, patient satisfaction and clinical outcomes will be measured.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: The Use of Cannabidiol (CBD) in Pain Reduction for Knee Osteoarthritis. A Double-Blind, Randomized Control Study
• Actual Study Start Date: June 22, 2022
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: June 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: CBD Group; The first cohort will take two 25mg cannabidiol (total dose: 50mg) Orally Disintegrating Tablets (CBD ODT) three times daily for a maximum dose of 150mg per day.	Drug: Cannabidiol (CBD); Patients will be dispensed enough 25mg cannabidiol (CBD) Orally Disintegrating Tablets (ODT) to take a standard dose of 50mg three times daily for 84 days.; Other Name: Cannabidiol
Placebo Comparator: Placebo Group; Cohort 2 will receive the same instructions, but with the placebo Orally Disintegrating Tablets (ODT) instead.	Drug: Placebo; 25mg Placebo ODT looks like the cannabidiol (CBD) Orally Disintegrating Tablets (ODT), but contains no active ingredients.

Outcome Measures

Primary Outcome Measures :

1. VAS Pain Severity Score [ Time Frame: Day 1 ]
   A Visual Analogue Scale (VAS) will be used to measure differences in pain between patients receiving CBD with knee OA undergoing physiotherapy compared to patients who do not receive CBD. Patients rate their pain on a scale ranging from 0 (no pain) to 10 (worst pain imaginable). Total scores range from 0-10; higher scores indicates greater pain intensity.
2. VAS Pain Severity Score [ Time Frame: Day 2 ]
   A Visual Analogue Scale (VAS) will be used to measure differences in pain between patients receiving CBD with knee OA undergoing physiotherapy compared to patients who do not receive CBD. Patients rate their pain on a scale ranging from 0 (no pain) to 10 (worst pain imaginable). Total scores range from 0-10; higher scores indicates greater pain intensity.
3. VAS Pain Severity Score [ Time Frame: Day 7 ]
   A Visual Analogue Scale (VAS) will be used to measure differences in pain between patients receiving CBD with knee OA undergoing physiotherapy compared to patients who do not receive CBD. Patients rate their pain on a scale ranging from 0 (no pain) to 10 (worst pain imaginable). Total scores range from 0-10; higher scores indicates greater pain intensity.
4. VAS Pain Severity Score [ Time Frame: Day 14 ]
   A Visual Analogue Scale (VAS) will be used to measure differences in pain between patients receiving CBD with knee OA undergoing physiotherapy compared to patients who do not receive CBD. Patients rate their pain on a scale ranging from 0 (no pain) to 10 (worst pain imaginable). Total scores range from 0-10; higher scores indicates greater pain intensity.
5. VAS Pain Severity Score [ Time Frame: Day 28 ]
   A Visual Analogue Scale (VAS) will be used to measure differences in pain between patients receiving CBD with knee OA undergoing physiotherapy compared to patients who do not receive CBD. Patients rate their pain on a scale ranging from 0 (no pain) to 10 (worst pain imaginable). Total scores range from 0-10; higher scores indicates greater pain intensity.
6. VAS Pain Severity Score [ Time Frame: Day 42 ]
   A Visual Analogue Scale (VAS) will be used to measure differences in pain between patients receiving CBD with knee OA undergoing physiotherapy compared to patients who do not receive CBD. Patients rate their pain on a scale ranging from 0 (no pain) to 10 (worst pain imaginable). Total scores range from 0-10; higher scores indicates greater pain intensity.
7. VAS Pain Severity Score [ Time Frame: Day 84 ]
   A Visual Analogue Scale (VAS) will be used to measure differences in pain between patients receiving CBD with knee OA undergoing physiotherapy compared to patients who do not receive CBD. Patients rate their pain on a scale ranging from 0 (no pain) to 10 (worst pain imaginable). Total scores range from 0-10; higher scores indicates greater pain intensity.

Secondary Outcome Measures :

1. Knee Injury and Osteoarthritis Outcome Score (KOOS) [ Time Frame: Baseline ]

   KOOS is a knee-specific instrument, developed to assess patients' opinion about their knee and associated problems. The five patient-relevant subscales of KOOS are scored separately: Pain (9 items); Symptoms (7 items); ADL Function (17 items); Sport and Recreation Function (5 items); Quality of Life (4 items).

   Patients rank each item using a 5-piont Likert scale ranging from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores are calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems.

2. Knee Injury and Osteoarthritis Outcome Score (KOOS) [ Time Frame: Week 6 ]

   KOOS is a knee-specific instrument, developed to assess patients' opinion about their knee and associated problems. The five patient-relevant subscales of KOOS are scored separately: Pain (9 items); Symptoms (7 items); ADL Function (17 items); Sport and Recreation Function (5 items); Quality of Life (4 items).

   Patients rank each item using a 5-piont Likert scale ranging from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores are calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems.

3. Knee Injury and Osteoarthritis Outcome Score (KOOS) [ Time Frame: Week 12 ]

   KOOS is a knee-specific instrument, developed to assess patients' opinion about their knee and associated problems. The five patient-relevant subscales of KOOS are scored separately: Pain (9 items); Symptoms (7 items); ADL Function (17 items); Sport and Recreation Function (5 items); Quality of Life (4 items).

   Patients rank each item using a 5-piont Likert scale ranging from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores are calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems.

4. Knee Injury and Osteoarthritis Outcome Score (KOOS) [ Time Frame: Week 60 ]

   KOOS is a knee-specific instrument, developed to assess patients' opinion about their knee and associated problems. The five patient-relevant subscales of KOOS are scored separately: Pain (9 items); Symptoms (7 items); ADL Function (17 items); Sport and Recreation Function (5 items); Quality of Life (4 items).

   Patients rank each item using a 5-piont Likert scale ranging from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores are calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems.

5. VAS Satisfaction with Pain Management Score [ Time Frame: Day 1 ]
   A Visual Analogue Scale (VAS) will be used to measure patient satisfaction with pain management. Patients rate their satisfaction on a scale ranging from 0 (no satisfaction) to 10 (as satisfied as possible). Total scores range from 0-10; higher scores indicates greater satisfaction with pain management.
6. VAS Satisfaction with Pain Management Score [ Time Frame: Day 2 ]
   A Visual Analogue Scale (VAS) will be used to measure patient satisfaction with pain management. Patients rate their satisfaction on a scale ranging from 0 (no satisfaction) to 10 (as satisfied as possible). Total scores range from 0-10; higher scores indicates greater satisfaction with pain management.
7. VAS Satisfaction with Pain Management Score [ Time Frame: Day 7 ]
   A Visual Analogue Scale (VAS) will be used to measure patient satisfaction with pain management. Patients rate their satisfaction on a scale ranging from 0 (no satisfaction) to 10 (as satisfied as possible). Total scores range from 0-10; higher scores indicates greater satisfaction with pain management.
8. VAS Satisfaction with Pain Management Score [ Time Frame: Day 14 ]
   A Visual Analogue Scale (VAS) will be used to measure patient satisfaction with pain management. Patients rate their satisfaction on a scale ranging from 0 (no satisfaction) to 10 (as satisfied as possible). Total scores range from 0-10; higher scores indicates greater satisfaction with pain management.
9. VAS Satisfaction with Pain Management Score [ Time Frame: Day 28 ]
   A Visual Analogue Scale (VAS) will be used to measure patient satisfaction with pain management. Patients rate their satisfaction on a scale ranging from 0 (no satisfaction) to 10 (as satisfied as possible). Total scores range from 0-10; higher scores indicates greater satisfaction with pain management.
10. VAS Satisfaction with Pain Management Score [ Time Frame: Day 42 ]
    A Visual Analogue Scale (VAS) will be used to measure patient satisfaction with pain management. Patients rate their satisfaction on a scale ranging from 0 (no satisfaction) to 10 (as satisfied as possible). Total scores range from 0-10; higher scores indicates greater satisfaction with pain management.
11. VAS Satisfaction with Pain Management Score [ Time Frame: Day 84 ]
    A Visual Analogue Scale (VAS) will be used to measure patient satisfaction with pain management. Patients rate their satisfaction on a scale ranging from 0 (no satisfaction) to 10 (as satisfied as possible). Total scores range from 0-10; higher scores indicates greater satisfaction with pain management.
12. Number of Patients Requiring Rescue Corticosteroid Use [ Time Frame: Up to Week 60 ]

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients presenting with knee osteoarthritis (KL Grade II-III)
• Knee pain for at least three months, occurring in at least half of the days in that period
• VAS ≥ 4
• Patients ages 40-75, inclusive
• If female patients are pre-menopausal they must be currently practicing effective forms of two types of birth control, which are defined as those, alone or in combination, that result in a low failure rate (less than 1% per year) when used consistently and correctly
• Male patients must be using an effective form of contraception

Exclusion Criteria:

• Knee Injections within the last 3 months (cortisone, PRP, hyaluronic acid)
• Legally incompetent or mentally impaired (e.g., minors, Alzheimer's subjects, dementia, etc.)
• Younger than 40 years of age
• Older than 75 years of age
• Any patient considered a vulnerable subject: pregnant women or fetuses, children, cognitively impaired adults, prisoners
• History of cannabis abuse or dependence
• History of coagulation abnormalities and thromboembolic disease or current abnormal coagulation test values
• History of stroke or acute coronary syndromes within 3 months
• Abnormal coagulation profile
• Renal failure (serum creatinine > 250 μmol/L [2.83 mg/dL]) or liver cirrhosis
• Patients that have been on opioid management for any reason just prior to the study
• Patients with known inflammatory arthritis (such as rheumatoid arthritis, gout, pseudogout etc)
• Patients with a large effusion
• Patients with a BMI > 35
• Patients meeting the DSM-V for major psychiatric illness, such as bipolar disorder
• Patients diagnosed with major depression, psychosis, or substance abuse disorder
• Patients with current or a history of suicidal ideation
• Breastfeeding females
• Abnormal LFTs
• Patients with major neurological disorders, such as dementia, Parkinson's disease, cognitive impairment, epilepsy, history of traumatic brain/head injury, or seizures
• Patients with moderate (Child-Pugh B) and severe hepatic impairment (Child-Pugh C).
• Patients taking moderate or strong inhibitors of CYP3A4 and CYP2C19 (listed below) concomitantly will be considered for exclusion if determined to be clinically significant by the treating physicians
• Patients taking strong CYP3A4 and CYP2C19 inducers (listed below) concomitantly will be considered for exclusion if determined to be clinically significant by the treating physicians
• Patients taking substrates of UTG1A9, UTGB17, CYP2A1, CYP2B6, CYP2C8, CYP2C9 and CYP2C19 (listed below) concomitantly will be considered for exclusion if determined to be clinically significant by the treating physicians

Contacts and Locations

Contacts

Contact: Michael J Alaia, MD; 646-501-7223; michael.alaia@nyulangone.org

Contact: Isabel Chalem; isabel.chalem@nyulangone.org

Locations

United States, New York

NYU Langone Health; Recruiting

New York, New York, United States, 10016

Principal Investigator: Michael Alaia, MD

Sponsors and Collaborators

NYU Langone Health

Orcosa Inc.

Investigators

• Principal Investigator: Michael J Alaia, MD; NYU Langone Health

More Information

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT05020028
• Other Study ID Numbers: 21-00334
• First Posted: August 25, 2021
• Last Update Posted: May 24, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: The data will only be available to the researchers involved in this study.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Cannabidiol; Anticonvulsants