Investigation of Cannabidiol for Reduction of NeuroInflammation in Chronic Back Pain (CBD)

In this research, the study team will use brain imaging to evaluate the presence of neuroinflammation in the brains and spinal cords of patients with low back pain, and whether CBD effects levels of neuroinflammation. The efficacy of CBD use for low back pain treatment will also be evaluated by observing whether CBD administration will reduce neuroinflammation and low back pain symptoms.

Study Overview

• Status: Terminated
• Conditions: Back Pain, Low
• Intervention / Treatment: Drug: Cannabidiol

Detailed Description

The goal of this research study is to test whether "glial cells" (the immune cells of the brain and spinal cord) that are active in patients with low back pain can be reduced with CBD. Previous studies have showed that patients with chronic low back pain demonstrated elevations in brain levels of the 18kDa translocator protein (TSPO), a marker of glial activation.

To test this hypothesis, the study team will image the brains and spinal cords of patients suffering from low back pain using integrated magnetic resonance- positron emission tomography (MR-PET), and a radiotracer called [11C]PBR28, which tracks levels of glial activation.

The efficacy of CBD as a treatment for chronic low back pain will be evaluated. The study team will observe whether 4 weeks of CBD treatment may reduce glial activation along with self-reported low back pain symptoms. To this end, patients will be evaluated clinically and/or re-scanned after completing the 4-week trial of minocycline.

This study will be enrolling individuals who have been suffering from chronic low back pain.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age ≥ 18 and ≤ 75;
• the ability to give written, informed consent;
• ongoing pain that averaged at least 4, on a 0-10 scale of pain during a typical week, and present for at least 50% of days during a typical week;
• fluency in English;
• on a stable pain treatment (pharmacological or otherwise) for the previous four weeks.
• Medical records confirming diagnosis of low back pain
• Chronic low back pain, ongoing for at least 6 months prior to enrollment.

Exclusion Criteria:

• outpatient surgery within 2 months and inpatient surgery within 6 months from the time of scanning;
• 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
• contraindications to functional magnetic resonance imaging scanning and positron emission tomography 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);
• current or past history within the last 5 years of major medical illness not affecting the central nervous system, other than chronic pain;
• implanted spinal cord stimulator (SCS) for pain treatment;
• any history of neurological illness or major medical illness affecting the central nervous system, unless clearly resolved without long-term consequences;
• current or past history of major psychiatric illness;
• PTSD, depression, and anxiety are exclusion criteria only if the conditions were so severe as to require hospitalization in the past year.
• pregnancy or breast feeding;
• history of head trauma requiring hospitalization;
• major cardiac event within the past 10 years;
• any use of recreational drugs in the past 3 months
• any marijuana use, medical or recreational, in the past 3 months
• an abnormal physical exam (e.g., peripheral edema);
• routine use of opioids ≥ 60 mg morphine equivalents;
• use of immunosuppressive medications, such as prednisone, TNF medications within 2 weeks of the visit;
• current bacterial or viral infection;
• Any other contraindications to CBD administration noted by the study physician.
• If undergoing blood draws through an arterial line during scan, contraindications to placement of arterial line, such as abnormal result on modified Allen's test on both hands; Raynaud syndrome; bleeding disorder; use of anticoagulants such as Coumadin, Plavix or Lovenox

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CBD Arm; Evaluation with Magnetic Resonance-Positron Emission Tomography Imaging and/or behavioral pain assessment before and after a 4-week trial of a liquid formulation of CBD.

Drug: Cannabidiol; 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. The recommended starting dosage is 2.5mg/kg taken twice daily (5mg/kg/day). After one week, the dosage will be increased to a maintenance dosage of 10 mg/kg twice daily (20 mg/kg/day). At the end of the first week, the patient will increase the dose to 10 mg/kg twice daily for the following week.; Other Names: Epidiolex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Brain Positron Emission Tomography Signal	The investigators will test for the presence of a significant treatment effect in the brain [11C]PBR28 signal.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Pain Outcomes as Measured by Self Report on a 0-10 Numerical Pain Rating Scale (Worst Pain in the Past 24 Hours).	The investigators will test for the presence of a significant treatment effect in pain outcomes on a self reported numerical (0-10) pain rating scale. Higher number indicates worse pain.	4 weeks

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Jodi Gilman, PhD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2019
• Primary Completion (Actual): November 23, 2020
• Study Completion (Actual): November 23, 2020

Study Registration Dates

• First Submitted: March 25, 2019
• First Submitted That Met QC Criteria: March 25, 2019
• First Posted (Actual): March 27, 2019

Study Record Updates

• Last Update Posted (Actual): May 4, 2022
• Last Update Submitted That Met QC Criteria: April 12, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: 2019P000852

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: We will make this data available upon request
• IPD Sharing Time Frame: Data will become available after 2 years
• IPD Sharing Access Criteria: Researchers, not for commercial use
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes