Clinical trial NCT03106740: Evaluating the Role of Neuroinflammation in Low Back Pain
Official title: Imaging Glia-mediated NeuroInflammation and Treatment Efficacy (the IGNITE Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Low Back Pain
Back Pain With Radiation
Back Pain Without Radiation
Back Pain Lower Back Chronic
Back Ache
Pain, Chronic
Keywords: Microglia
Minocycline
Magnetic Resonance Imaging
Positron Emission Tomography
Pain
Astrocytes
Glia
Human
Back Pain
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2017-04-10
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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. The efficacy of minocycline use for low back pain treatment will also be evaluated by observing whether short-term minocycline administration will reduce neuroinflammation and low back pain symptoms.

Detailed description: The goal of this research study is to evaluate whether the central nervous systems of those with low back pain are different from those of healthy, pain-free individuals. Specifically, the researchers will test whether "glial cells" (the immune cells of the brain and spinal cord) are more active in patients with low back pain than in healthy volunteers. The investigators' previous study 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 minocycline as a treatment for chronic low back pain will also be evaluated. A recent study demonstrated a statistically significant reduction in pain in those with lumbar radiculopathy after treatment with minocycline, leading the investigators of this study to believe that minocycline may have potential efficacy in treating other back pain populations.

The study team will observe whether a short course of minocycline hydrochloride 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 a 2-week trial of minocycline or placebo (a sugar pill).

This study will be enrolling individuals who have been suffering from sub-acute (short-term) and chronic low back pain.

Eligibility criteria: Inclusion Criteria:

* the ability to give written informed consent
* fluency in English
* on a stable pain treatment
* Chronic or sub-acute low back pain

Exclusion Criteria:

* no interventional pain procedures during drug trial
* contraindications to MRI 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)
* pregnancy or breast feeding
* any use of recreational drugs in the past 6 months
* allergy to minocycline or other tetracyclines, or taking medications known to interact with minocycline
* any other contraindications to minocycline administration

Primary outcomes:
measure: Changes in Thalamic Standardized Uptake Value Ratio (SUVR)
timeFrame: The outcome measure was assessed in two time points, before and after a two-week treatment period.
Secondary outcomes:
measure: Changes in Spinal PET Signal
timeFrame: 2 weeks
measure: Daily Pain Ratings (as Measured by the Modified Brief Pain Inventory (BPI) Severity Subscale)
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Charlestown
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Marco L Loggia, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Loggia ML, Chonde DB, Akeju O, Arabasz G, Catana C, Edwards RR, Hill E, Hsu S, Izquierdo-Garcia D, Ji RR, Riley M, Wasan AD, Zurcher NR, Albrecht DS, Vangel MG, Rosen BR, Napadow V, Hooker JM. Evidence for brain glial activation in chronic pain patients. Brain. 2015 Mar;138(Pt 3):604-15. doi: 10.1093/brain/awu377. Epub 2015 Jan 12.
citation: Vanelderen P, Van Zundert J, Kozicz T, Puylaert M, De Vooght P, Mestrum R, Heylen R, Roubos E, Vissers K. Effect of minocycline on lumbar radicular neuropathic pain: a randomized, placebo-controlled, double-blind clinical trial with amitriptyline as a comparator. Anesthesiology. 2015 Feb;122(2):399-406. doi: 10.1097/ALN.0000000000000508.