Cannabidiol for Reduction of Brain Neuroinflammation
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorMassachusetts General Hospital
About this trial
This study will investigate whether cannabidiol (CBD), the primary centrally and peripherally active non-intoxicating compound in the cannabis plant, exerts anti-neuroinflammatory effects in patients with chronic low back pain (cLBP) with or without mild-to-moderate depression.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 and ≤ 75;
The ability to give written, informed consent;
Fluency in English;
Average worst daily pain of at least 4 on a 0-10 scale of pain intensity, during a typical day. Pain needs to be present for at least 50% of days during a typical week;
Disqualifiers
Outpatient surgery within 2 weeks and inpatient surgery within 1 month of the time of scanning (this timeframe may be extended if they are not fully recovered from the surgery);
Elevated baseline transaminase (ALT and AST) levels above 3 times the Upper Limit of Normal (ULN), accompanied by elevations in bilirubin above 2 times the ULN;
Any interventional pain procedures within 6 weeks prior to scanning procedure or at any point during study enrollment;
Surgical intervention or introduction/change in opioid regimen at any point during study enrollment;
Trial design
Design model
Parallel
Treatments tested in this trial
CBD
DrugEpidiolex, an agent within the anti-epileptic drug class, will be used. Epidiolex, Greenwich Biosciences Inc.'s CBD formulation, is a 100 mg/mL purified oral solution, dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring. The drug is formulated from extracts prepared from Cannabis sativa L. plants that have a defined chemical profile and contain consistent levels of CBD as the principal phytocannabinoid. Extracts from these plants are processed to yield pure (\>95%) CBD that typically contains less than 0.5% (w/w) THC. Cannabidiol is the active ingredient in Epidiolex; inactive ingredients include dehydrated alcohol, sesame seed oil, strawberry flavor, and sucralose. Of note, CBD has no psychoactive properties.
Placebo
Other interventionPlacebo CBD will be identical to the active CBD, a 100 mg/mL purified oral solution, dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring, but with no CBD.
Treatment groups
80 Participants
are divided into 2 treatment groupsGroup A: Cannabidiol (CBD)Experimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Changes in Neuroinflammation in the Thalamus
The investigators will test for the presence of a significant treatment effect in the brain \[11C\]PBR28 signal in the thalamus, in order to test whether patients in the CBD arm will demonstrate significantly larger treatment-related reductions in neuroinflammation, compared to patients in the placebo arm.
Time frame
Change from Baseline to Week 4Secondary outcomes
1
Changes in Neuroinflammation in Limbic Regions
The investigators will test for the presence of a significant treatment effect in the brain \[11C\]PBR28 in limbic regions (pgACC, aMCC), in order to test whether patients in the CBD arm will demonstrate significantly larger treatment-related reductions in neuroinflammation, compared to patients in the placebo arm.
Time frame
Change from Baseline to Week 42
Correlation Between Reductions in Thalamic [11C]PBR28 PET Signal and Reductions in Clinical Pain Ratings
The investigators will test whether reductions in thalamic \[11C\]PBR28 PET signal correlate with reductions in clinical pain ratings, as assessed by the "worst pain" item of the Brief Pain Inventory - Short Form. The "worst pain" item's scale ranges from 0 - 10, with a higher score indicating worse pain intensity.
Time frame
Change from Baseline to Week 43
Correlation Between Reductions in Limbic [11C]PBR28 PET Signal and Reductions in Depressive Symptoms
The investigators will test whether reductions in pgACC/aMCC \[11C\]PBR28 PET signal (as measured by Standardized Uptake Value Ratio) correlate with reductions in depressive symptoms, as measured by the Beck Depression Inventory-II. The Beck Depression Inventory-II scale ranges from 0 - 63, with a higher score indicating greater depression.
Time frame
Change from Baseline to Week 44
Change in Clinical Pain Ratings
The "worst pain" item of the Brief Pain Inventory - Short Form will be used daily to assess pain intensity. The scale ranges from 0 - 10, with a higher score indicating worse pain intensity.
Time frame
Change from average score during the 7 days prior to treatment (Baseline) to average score during the final week of treatmentOther outcomes
1
Change in Functional Brain Reward Circuitry [Exploratory]
The Monetary Incentive Delay task will be used to assess striatal response to the anticipation and/or consumption of rewards/losses.
Time frame
Change from Baseline to Week 42
Change in Pain Severity & Interference with Daily Functioning [Exploratory]
The full Brief Pain Inventory - Short Form will be used to assess pain severity and its interference with daily functioning. Pain severity is assessed on a scale from 0 - 10, with a higher score indicating more severe pain. Daily functioning is also assessed on a scale from 0 - 10, with a higher score indicating that pain more greatly interferes with functioning.
Time frame
Change from Baseline to Week 43
Change in Pain Catastrophizing [Exploratory]
The Pain Catastrophizing Scale will be used to assess pain catastrophizing. The scale ranges from 0 - 52, with a higher score indicating greater catastrophic thinking.
Time frame
Change from Baseline to Week 44
Change in Neuropathic Pain Components [Exploratory]
The PainDETECT questionnaire will be used to assess neuropathic components of pain. The scale ranges from -1 to 38, with a higher score indicating more neuropathic-like symptoms.
Time frame
Change from Baseline to Week 4Sponsors and contacts
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Source ClinicalTrials.gov