Back Pain, Depressive Symptoms
Conditions
Keywords
back pain, depression, depressive symptoms, cannabis, cannabidiol
Brief summary
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.
Detailed description
This is a randomized, double-blind, 2-arm mechanistic trial that seeks to assess the effects of CBD and placebo in patients with cLBP with and without mild-to-moderate depression, using integrated positron emission tomography / magnetic resonance imaging (PET/MRI) scans. The use of integrated PET/MRI will make it possible to simultaneously evaluate neuroinflammation (using \[11C\]PBR28, a second-generation radioligand for TSPO) and striatal function (using the Monetary Incentive Delay task, a validated fMRI task that probes behavioral and neural responses to rewards and losses).
Interventions
DRUGCBD
Epidiolex, 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.
OTHERPlacebo
Placebo 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.
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 and ≤ 75; 2. The ability to give written, informed consent; 3. Fluency in English; 4. 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; 5. On a stable pain treatment (pharmacological or otherwise) for the previous four weeks; 6. Diagnosis of chronic low back pain, ongoing for at least 6 months prior to enrollment. 7. High or mixed affinity binding to \[11C\]PBR28 identified by the Ala147Thr TSPO polymorphism in the TSPO gene (rs6971)
Exclusion criteria
1. 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); 2. 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; 3. Any interventional pain procedures within 6 weeks prior to scanning procedure or at any point during study enrollment; 4. Surgical intervention or introduction/change in opioid regimen at any point during study enrollment; 5. Contraindications to fMRI scanning and PET scanning (including presence of a cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head or previous neurosurgery, prosthetic heart valves, claustrophobia); 6. Implanted spinal cord stimulator (SCS) for pain treatment; 7. Any history of neurological illness or major medical illness, unless clearly resolved without long-term consequences; 8. Current or past history of major psychiatric illness (PTSD, depression, and anxiety are
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Neuroinflammation in the Thalamus | Change from Baseline to Week 4 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Neuroinflammation in Limbic Regions | Change from Baseline to Week 4 | 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. |
| Correlation Between Reductions in Thalamic [11C]PBR28 PET Signal and Reductions in Clinical Pain Ratings | Change from Baseline to Week 4 | 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. |
| Correlation Between Reductions in Limbic [11C]PBR28 PET Signal and Reductions in Depressive Symptoms | Change from Baseline to Week 4 | 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. |
| Change in Clinical Pain Ratings | Change from average score during the 7 days prior to treatment (Baseline) to average score during the final week of treatment | 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. |
| Change in Pain Bothersomeness | Change from average score during the 7 days prior to treatment (Baseline) to average score during the final week of treatment | Pain bothersomeness will be assessed daily on a scale from 0 - 10, with a higher score indicating greater bothersomeness. |
| Change in Depressive Symptoms | Change from Baseline to Week 4 | The Beck Depression Inventory-II will be used to assess symptoms of depression. The scale ranges from 0 - 63, with a higher score indicating greater depression. |
| Patient Global Impression of Change | Week 4 | The Patient Global Impression of Change scale will be used to assess participants' perceptions about their global improvement related to their low back pain. The scale ranges from 0 - 7, with a higher score indicating greater overall improvement. |
Countries
United States
Contacts
CONTACTJodi M Gilman, PhD
Outcome results
None listed