Therapeutic Response of Cannabidiol in Rheumatoid Arthritis

• ClinicalTrials.gov Identifier: NCT04911127
• Recruitment Status: Recruiting
• First Posted: June 2, 2021
• Last Update Posted: November 9, 2022
• Sponsor: University of California, Los Angeles
• Information provided by (Responsible Party): Veena Ranganath, MD, MS, University of California, Los Angeles

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis; Cannabis	Drug: 200mg Cannabidiol by capsules twice daily; Drug: 400mg Cannabidiol by capsules twice daily; Drug: Placebo capsules	Phase 1; Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Double Blind, Placebo-Controlled Trial to Evaluate the Safety and Tolerability of Cannabidiol (CBD) in Moderate to Severe Rheumatoid Arthritis
• Actual Study Start Date: October 5, 2021
• Estimated Primary Completion Date: June 10, 2024
• Estimated Study Completion Date: June 10, 2025

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Participants will take capsules containing medium chain triglyceride (MCT) oil	Drug: Placebo capsules; MCT oil capsules as placebo for CBD; Other Name: Placebo
Experimental: 200mg CBD twice daily; Participants will take capsules containing cannabidiol amounting to 200mg CBD twice daily	Drug: 200mg Cannabidiol by capsules twice daily; 200mg twice daily via 50mg capsules; Other Name: CBD
Experimental: 400 mg CBD twice daily; Participants will take capsules containing cannabidiol amounting to 400mg CBD twice daily	Drug: 400mg Cannabidiol by capsules twice daily; 400mg twice daily via 50mg capsules; Other Name: CBD

Outcome Measures

Primary Outcome Measures :

1. Change from Baseline in Disease Activity Score (DAS28/ESR) [ Time Frame: Baseline, 12 Weeks ]
   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.
2. Tolerability as assessed by participant attrition [ Time Frame: 12 weeks ]
   Tolerability will be evaluated based on the number of participants that drop out due to treatment emergent adverse events or serious adverse events.

Secondary Outcome Measures :

1. Change in Power Doppler Synovitis Score (PDUS) [ Time Frame: Baseline, 12 weeks ]
   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.
2. Change in Grey Scale Synovial Hypertrophy Score (GSUS) [ Time Frame: Baseline, 12 weeks ]
   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.

Other Outcome Measures:

1. Change in inflammatory cytokine and chemokine concentrations [ Time Frame: Baseline, 12 weeks ]
   Inflammatory cytokines and chemokine concentrations from plasma will be evaluated using multiplex cytokine array.
2. Change in white blood cell (WBC) subset percentages [ Time Frame: Baseline, 12 weeks ]
   WBC subset percentages will be assessed via flow cytometry.
3. Change in Clinical Disease Activity Index (CDAI) [ Time Frame: Baseline, 12 weeks ]
   CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. The total CDAI score range is 0-76, where higher scores indicate increased disease activity.
4. Change in Health Assessment Questionnaire - Disability Index (HAQ-DI) [ Time Frame: Baseline, 12 weeks ]
   The HAQ-DI is a patient-reported assessment of physical function that includes 20 items in eight categories representing a comprehensive set of functional activities, including dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Patients are asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst), with a higher score representing a high-dependency disability.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Study Coordinator; 310-825-9956; vranganath@mednet.ucla.edu

Locations

United States, California

UCLA David Geffen School of Medicine, Division of Rheumatology; Recruiting

Los Angeles, California, United States, 90095

Contact: Nicolette Morris 310-825-9956

Principal Investigator: Veena K Ranganath, M.D.

Principal Investigator: Ziva Cooper, PhD

Sponsors and Collaborators

University of California, Los Angeles

Investigators

• Principal Investigator: Ziva Cooper, PhD; University of California, Los Angeles
• Principal Investigator: Veena Ranganath, MD, MS; University of California, Los Angeles

More Information

• Responsible Party: Veena Ranganath, MD, MS, Principal Investigator, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT04911127
• Other Study ID Numbers: 19-01551; P64-01-003 ( Other Grant/Funding Number: CMCR )
• First Posted: June 2, 2021
• Last Update Posted: November 9, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Cannabidiol; Anticonvulsants