Therapeutic Response of Cannabidiol in Rheumatoid Arthritis

Study Overview
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Brief Summary
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The study will randomly assign Rheumatoid Arthritis (RA) patients on stable RA therapy to either placebo or cannabidiol (CBD). The overall goal of this proposal is to examine the efficacy and safety of CBD treatment as adjunctive to the medical management of RA patients.

Detailed Description
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This is a randomized, placebo-controlled, double-blind clinical trial at the University of California, Los Angeles evaluating the efficacy, safety, and tolerability of oral cannabidiol (CBD) as adjunctive for rheumatoid arthritis (RA) patients on stable therapy. Patients with moderate to severe RA meeting study inclusion criteria will be randomly assigned to one of three treatment groups (CBD 200 mg BID, CBD 400 mg BID, or placebo). Patients in all groups will receive CBD or placebo under observation for 12 weeks with an additional follow-up phone call occurring 4 weeks after.

Official Title
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Randomized, Double Blind, Placebo-Controlled Trial to Evaluate the Safety and Tolerability of Cannabidiol (CBD) in Moderate to Severe Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis, Cannabis

Intervention / Treatment
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* Drug: 200mg Cannabidiol by capsules twice daily
* Drug: 400mg Cannabidiol by capsules twice daily
* Drug: Placebo capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 Classification Criteria for Rheumatoid Arthritis Disease activity score (DAS28) >= 3.2 Age >= 18 Stable RA therapy for 12 weeks prior to baseline Power Doppler Score >= 5 (for the PDUS 34 joint score) Must use at least one highly effective method of contraception Written informed consent Exclusion Criteria: Prior exposure to cannabis <= 28 days prior to baseline Current diagnosed substance use disorders (including Alcohol Use Disorder) Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment Chronic infections >10mg of prednisone daily use Daily use of central nervous system (CNS) depressant medications (e.g. sedatives, hypnotics [zolpidem, temazepam, alprazolam, lorazepam, diphenhydramine etc.]) Women who are pregnant, planning to become pregnant, or breast feeding Sexually active subjects and their partners who are of childbearing potential (ie, neither surgically sterile nor postmenopausal) and not agreeing to use adequate contraception Deemed unsafe by the investigator History of an allergic reaction or adverse reaction to cannabis is exclusionary.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will take capsules containing medium chain triglyceride (MCT) oil | Drug: Placebo capsules<br>* MCT oil capsules as placebo for CBD<br>* Other names: Placebo;|
| Experimental: 200mg CBD twice daily<br>Participants will take capsules containing cannabidiol amounting to 200mg CBD twice daily | Drug: 200mg Cannabidiol by capsules twice daily<br>* 200mg twice daily via 50mg capsules<br>* Other names: CBD;|
| Experimental: 400 mg CBD twice daily<br>Participants will take capsules containing cannabidiol amounting to 400mg CBD twice daily | Drug: 400mg Cannabidiol by capsules twice daily<br>* 400mg twice daily via 50mg capsules<br>* Other names: CBD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Disease Activity Score (DAS28/ESR) | The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes swollen joint counts (SJC) and tender joint counts (TJC), both scored 0-28 (higher scores indicate higher disease activity), as well as acute phase response (APR) determined as erythrocyte sedimentation rate (ESR), and general health (GH), both scored 1-100 (higher scores indicate higher disease activity). DAS28 was calculated according to the following formula: DAS28 equals (=) [0.56 multiplied by (*) the square root (√) of TJC] plus (+) [0.28 * √ of SJC] + (0.70 * the natural logarithm (ln) ESR in millimeters per hour (mm/h)] + [0.014 * GH in mm visual analogue assessment (VAS)]. A negative change from randomization indicated improvement. | Baseline, 12 Weeks | 
| Tolerability as assessed by participant attrition | Tolerability will be evaluated based on the number of participants that drop out due to treatment emergent adverse events or serious adverse events. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Power Doppler Synovitis Score (PDUS) | 34 joints will be evaluated using a 0 to 3 point scale for each joint and the sum of these represents PDUS. PDUS ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. A higher value of the total score for PDUS represents more severe disease level. | Baseline, 12 weeks | 
| Change in Grey Scale Synovial Hypertrophy Score (GSUS) | 34 joints will be evaluated using a 0 to 3 point scale for each joint and the sum of these represents GSUS. GSUS ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. A higher value of the total score for GSUS represents more severe disease level. | Baseline, 12 weeks |