CBD for Chronic Radicular Pain on Chronic Opioid Therapy (COT)

Study Overview
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Brief Summary
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This double-blind, placebo-controlled, exploratory trial is designed to compare effects of oral CBD 600mg to placebo (PCB) in 20 outpatients with chronic spinal radiculopathies (without co-occurring Opioid Use Disorder), maintained on stable opioid analgesics for a minimum of 1 month. The trial duration will be approximately 2 weeks (from the point of randomization) of daily CBD 600mg vs placebo. Safety and tolerability of CBD will be assessed throughout the trial. The secondary efficacy outcome is change in pain outcomes from baseline to end of the treatment period at 2-weeks post-randomization/initiation of treatment with a Mixed Model for Repeated Measures (MMRM) statistical analysis performed to assess between group treatment effects of CBD relative to placebo.

Official Title
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A Phase I/II, Randomized, Double-blind, Placebo-controlled, Single-center Study of the Effects of Cannabidiol (CBD) on Opioid Plasma Levels in Participants With Chronic Radiculopathic Pain Syndromes Maintained on Chronic Opioid Therapy (COT)

Conditions
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Radiculopathy

Intervention / Treatment
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* Drug: Cannabidiol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged ≥18 Diagnosis of radicular CNCP (i.e. lumbar, cervical, thoracic) Maintained on stable dose opioid therapy for a minimum of 1 month o Note: Morphine Equivalent Daily Dose (MEDD) will be calculated using 2 reference documents: Guideline and conversion table to calculate MEDD from Centers for Medicaid and Medicare Services (CMS); Guidelines from the Centers for Disease Control and Prevention (CDC) intended for calculating total daily dose of opioids for safer dosage of opioid pharmacotherapy Able to provide voluntary informed consent If a woman of childbearing potential or a man, are willing to use approved form of contraception from screening for duration of the trial Exclusion Criteria: Exclusionary medical conditions (e.g., unstable cardiac, hepatic, renal, neurologic illness) or any medical illness that in the opinion of the study physician poses a potential medical danger to the participant Exclusionary laboratory abnormalities (clinically significant abnormalities of complete blood count or chemistries, significantly impaired liver function) Current substance use disorder (including Opioid Use Disorder) other than nicotine or caffeine At screening, a positive urine toxicology test for: amphetamines (AMP), barbiturates (BAR), buprenorphine (BUP), benzodiazepines (BZO), cocaine (COC), 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (MET), methadone (MTD), phencyclidine (PCP), and tetrahydrocannabinol (THC) At screening, an alcohol level greater than 0 on a breathalyzer Severe psychiatric conditions including past or current DSM5 diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder Current significant suicidality (assessed using the C-SSRS), any suicidal behavior in the past 12 months, or any history of suicide attempts Current use of recreational or medical cannabis or any product containing CBD Pregnancy or lactation Current use of concomitant medications metabolized primarily by CYP2C19 isoenzymes Current use of concomitant medications significantly or primarily metabolized by CYP3A4 with the potential for adverse drug-drug interactions with CBD (i.e., ketoconazole, rifampicin) Current use of concomitant medications with a narrow therapeutic window significantly or primarily metabolized by CYP2C9 with the potential for adverse drug-drug interactions with CBD (i.e., warfarin) Current use of concomitant medications known to have adverse drug-drug interactions with CBD (i.e., valproate) or the potential to cause significant drug-drug interactions (i.e., clobazam). Known allergy to CBD or any ingredient of the study compound Currently enrolled in a clinical trial assessing the effects of an anti-pain intervention

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cannabidiol (CBD)<br> | Drug: Cannabidiol<br>* 600 mg oral daily use (each capsule of active drug contains 50 mg of CBD)<br>|
| Placebo Comparator: Placebo (PCB)<br> | Drug: Placebo<br>* identical capsules containing placebo (taken daily by mouth)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Opioid Analgesic Plasma Levels | Opioid (i.e. the particular opioid used by a participant) analgesic plasma levels will be determined via High Performance Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS). | Baseline, Week 2 Post-Initiation of Treatment | 
| Change in CBD Plasma Levels | CBD plasma levels will be determined via High Performance Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS). | Day 1 Post-Initiation of Treatment, Week 2 Post-Initiation of Treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Score on Pain Catastrophizing Scale (PCS) | PCS consists of 13 statements describing different thoughts and feelings that may be associated with pain. The degree to which one has these thoughts and feelings when experiencing pain is indicated on a scale of 0 (not at all) to 4 (all the time). The total range of score is 0-52, with a higher score indicating more frequent negative thoughts. | Baseline, Week 2 Post-Initiation of Treatment | 
| Change in Brief Pain Inventory (BPI) Score | BPI - Short Form is a self-administered questionnaire. It evaluates: Pain intensity: 4 questions answered on a Likert scale of 0 (no pain) to 10 (pain as bad as you can imagine). Pain-related interference: 7 categories answered on a Likert scale of 0 (does not interfere) to 10 (completely interferes). The composite mean of these scores is used as the total pain interference score: the total score ranges from 0-55; higher scores indicate greater pain interference. | Baseline, Week 2 Post-Initiation of Treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cannabidiol