Morrissey Erin J, Alshelh Zeynab, Knight Paulina C, Saha Atreyi, Kim Minhae, Torrado-Carvajal Angel, Zhang Yi, Edwards Robert R, Pike Chelsea, Locascio Joseph J, Napadow Vitaly, Loggia Marco L
MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Medical Image Analysis and Biometry Laboratory, Universidad Rey Juan Carlos, Madrid, Spain.
Contemp Clin Trials. 2023 Mar;126:107087. doi: 10.1016/j.cct.2023.107087. Epub 2023 Jan 16.
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.
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 [C]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.
ClinicalTrials.gov (NCT03106740).
临床前研究以及最近的临床影像学研究均表明，胶质细胞介导的神经炎症可能与慢性疼痛有关，因此可能是一个潜在的治疗靶点。然而，目前尚不清楚调节神经炎症是否能有效减轻人类的疼痛。本试验检验了以下假设：米诺环素，一种美国食品药品监督管理局（FDA）批准的四环素类抗生素，在动物体内是有效的胶质细胞抑制剂，可减轻神经炎症，并可能减轻慢性下腰痛患者的疼痛症状。
本研究是一项随机、双盲、安慰剂对照的临床试验。通过书面知情同意，招募年龄在18至75岁之间、确诊为慢性（≥6个月）下腰痛（cLBP）且自我报告的疼痛评分至少为十分之四（平均每周至少一半天数）的受试者。符合条件的受试者被随机分配接受为期14天的活性药物（米诺环素）或安慰剂治疗。治疗前后，使用[C]PBR28对受试者进行正电子发射断层扫描/磁共振成像（PET/MRI）联合扫描，[C]PBR28是一种用于18 kDa转位蛋白（TSPO）的第二代放射性示踪剂，在胶质细胞中高度表达，因此是神经炎症的一个假定标志物。通过在开始用药前7天以及整个14天治疗期间收集的每日调查来评估疼痛水平。将使用一般线性模型来评估疼痛水平，并确定治疗对脑（和脊髓）TSPO信号的影响。
ClinicalTrials.gov（NCT03106740）。
