Assessing the potential anti-neuroinflammatory effect of minocycline in chronic low back pain: Protocol for a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Both preclinical studies, and more recent clinical imaging studies, suggest that glia-mediated neuroinflammation may be implicated in chronic pain, and therefore might be a potential treatment target. However, it is currently unknown whether modulating neuroinflammation effectively alleviates pain in humans. This trial tests the hypothesis that minocycline, an FDA-approved tetracycline antibiotic and effective glial cell inhibitor in animals, reduces neuroinflammation and may reduce pain symptoms in humans with chronic low back pain. METHODS AND ANALYSIS: This study is a randomized, double-blind, placebo-controlled clinical trial. Subjects, aged 18-75, with a confirmed diagnosis of chronic (≥ six months) low back pain (cLBP) and a self-reported pain rating of at least four out of ten (for at least half of the days during an average week) are enrolled via written, informed consent. Eligible subjects are randomized to receive a 14-day course of either active drug (minocycline) or placebo. Before and after treatment, subjects are scanned with integrated Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) using [11C]PBR28, a second-generation radiotracer for the 18 kDa translocator protein (TSPO), which is highly expressed in glial cells and thus a putative marker of neuroinflammation. Pain levels are evaluated via daily surveys, collected seven days prior to the start of medication, and throughout the 14 days of treatment. General linear models will be used to assess pain levels and determine the treatment effect on brain (and spinal cord) TSPO signal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03106740).

Repurposing minocycline for COVID-19 management: mechanisms, opportunities, and challenges.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly grown into a public health emergency that has placed the national health systems as well as scientific research communities under enormous pressures. Drug repurposing or repositioning is a well-known strategy that seeks to deploy existing licensed drugs for newer indications and provides the quickest possible transition from bench to clinics for unmet therapeutic needs. Given the current, urgent, and dire need for effective therapies against novel coronavirus-19, this approach is particularly appealing. AREAS COVERED: Here, we review the significant anti-inflammatory, immunomodulatory, and antiviral properties of minocycline as potential mechanisms for efficacy against the novel coronavirus and highlight the promises and pitfalls of this approach. EXPERT OPINION: As compared to other agents being investigated for COVID-19, minocycline offers distinct advantages in terms of potential efficacy in patients with life-threatening acute respiratory distress syndrome (ARDS) and myocardial injury, well-known safety and interaction profile, relatively low costs, and widespread availability. We call upon public and private funders to facilitate urgent and rigorous research efforts before evidence-based recommendations for its widespread use can be made.