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

• ClinicalTrials.gov Identifier: NCT03891264
• Recruitment Status: Terminated
• First Posted: March 27, 2019
• Results First Posted: April 13, 2022
• Last Update Posted: May 4, 2022
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Jodi Gilman, Massachusetts General Hospital

Tracking Information

• First Submitted Date: March 25, 2019
• First Posted Date: March 27, 2019
• Results First Submitted Date: January 7, 2022
• Results First Posted Date: April 13, 2022
• Last Update Posted Date: May 4, 2022
• Actual Study Start Date: November 13, 2019
• Actual Primary Completion Date: November 23, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 9, 2022)

Changes in Brain Positron Emission Tomography Signal [ Time Frame: 4 weeks ]

The investigators will test for the presence of a significant treatment effect in the brain [11C]PBR28 signal.

Original Primary Outcome Measures (submitted: March 25, 2019)

Glial activation [ Time Frame: 4 weeks ]

Brain levels of the 18kDa translocator protein (TSPO)

Current Secondary Outcome Measures (submitted: March 22, 2022)

Changes in Pain Outcomes as Measured by Self Report on a 0-10 Numerical Pain Rating Scale (Worst Pain in the Past 24 Hours). [ Time Frame: 4 weeks ]

The investigators will test for the presence of a significant treatment effect in pain outcomes on a self reported numerical (0-10) pain rating scale. Higher number indicates worse pain.

Original Secondary Outcome Measures (submitted: March 25, 2019)

Pain Scores [ Time Frame: 4 weeks ]

PCS Pain Scale

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Investigation of Cannabidiol for Reduction of NeuroInflammation in Chronic Back Pain
• Official Title: Investigation of Cannabidiol for Reduction of NeuroInflammation in Chronic Back Pain
• 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.

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
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Back Pain, Low

Intervention

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

Study Arms

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.

Intervention: Drug: Cannabidiol

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 28, 2021): 7
• Original Estimated Enrollment (submitted: March 25, 2019): 20
• Actual Study Completion Date: November 23, 2020
• Actual Primary Completion Date: November 23, 2020 (Final data collection date for primary outcome measure)

Eligibility 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 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03891264
• Other Study ID Numbers: 2019P000852
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

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

• Current Responsible Party: Jodi Gilman, Massachusetts General Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Massachusetts General Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jodi Gilman, PhD; Massachusetts General Hospital

• PRS Account: Massachusetts General Hospital
• Verification Date: April 2022