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

• ClinicalTrials.gov Identifier: NCT03891264
• Recruitment Status: Recruiting
• First Posted: March 27, 2019
• Last Update Posted: November 2, 2020
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Jodi Gilman, Massachusetts General Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Back Pain, Low	Drug: Cannabidiol	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Investigation of Cannabidiol for Reduction of NeuroInflammation
• Actual Study Start Date: November 19, 2019
• Estimated Primary Completion Date: June 2021
• Estimated Study Completion Date: June 2021

Arms and Interventions

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 Name: Epidiolex

Outcome Measures

Primary Outcome Measures :

1. Changes in brain PET signal [ Time Frame: 4 weeks ]
   The investigators will test for the presence of a significant treatment effect in the brain [11C]PBR28 signal.

Secondary Outcome Measures :

1. Changes in pain outcomes as measured by self report on a 0-100 numerical pain rating scale. [ Time Frame: 4 weeks ]
   The investigators will test for the presence of a significant treatment effect in pain outcomes on a self reported numerical (0-100) pain rating scale.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 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);
• 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

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Contact: Jodi Gilman, PhD 617-643-7293 jgilman1@partners.org

Principal Investigator: Jodi M Gilman, PhD

Sponsors and Collaborators

Massachusetts General Hospital

More Information

• Responsible Party: Jodi Gilman, Associate Professor, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03891264
• Other Study ID Numbers: CBD_Pain_PET Trial
• First Posted: March 27, 2019
• Last Update Posted: November 2, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

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

• 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

Additional relevant MeSH terms:

Back Pain; Low Back Pain; Pain; Neurologic Manifestations; Epidiolex; Anticonvulsants