Evaluating the Role of Neuroinflammation in Low Back Pain

Phase 2

Completed

Conditions: Back Ache
Pain, Chronic
Back Pain Lower Back Chronic
Back Pain With Radiation
Back Pain Without Radiation
Low Back Pain

Interventions: Drug: Minocycline Hydrochloride 100mg Capsule
Other: Placebo Capsule
Diagnostic Test: Magnetic Resonance-Positron Emission Tomography Imaging

Registration Number: NCT03106740

Lead Sponsor: Marco Loggia

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Minocycline Arm	Minocycline Hydrochloride 100mg Capsule	Evaluation with Magnetic Resonance-Positron Emission Tomography Imaging and/or behavioral pain assessment before and after a 2-week trial of Minocycline Hydrochloride, 100mg capsule
Placebo Arm	Placebo Capsule	Evaluation with Magnetic Resonance-Positron Emission Tomography Imaging and/or behavioral pain assessment before and after 2 weeks of treatment with a placebo capsule.
Minocycline Arm	Magnetic Resonance-Positron Emission Tomography Imaging	Evaluation with Magnetic Resonance-Positron Emission Tomography Imaging and/or behavioral pain assessment before and after a 2-week trial of Minocycline Hydrochloride, 100mg capsule
Placebo Arm	Magnetic Resonance-Positron Emission Tomography Imaging	Evaluation with Magnetic Resonance-Positron Emission Tomography Imaging and/or behavioral pain assessment before and after 2 weeks of treatment with a placebo capsule.

Primary Outcome Measures

Name	Time	Method
Changes in Thalamic Standardized Uptake Value Ratio (SUVR)	The outcome measure was assessed in two time points, before and after a two-week treatment period.	The ratio of the standardized uptake value (SUV; mean radioactivity divided by the injected dose by weight) of the whole thalamus divided by the SUV of the whole brain (i.e., standardized uptake value ratio or SUVR) derived from the translocator protein positron emission tomography (TSPO-PET) signal. Higher SUVR might be indicative of higher neuroinflammation.

Secondary Outcome Measures

Name	Time	Method
Changes in Spinal PET Signal	2 weeks	The investigators will test for the presence of a significant treatment\*time interaction in the spinal \[11C\]PBR28 signal.
Daily Pain Ratings (as Measured by the Modified Brief Pain Inventory (BPI) Severity Subscale)	2 weeks	The investigators will test for the presence of a significant treatment\*time interaction in pain outcomes using the severity subscale of the Brief Pain Intensity, short form (range 0-10)