Field Joshua J, Kassim Adetola, Brandow Amanda, Embury Stephen H, Matsui Neil, Wilkerson Karina, Bryant Valencia, Zhang Liyun, Simpson Pippa, DeBaun Michael R
Medical Sciences Institute, Versiti Wisconsin, Milwaukee, WI.
Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.
Blood Adv. 2020 Mar 24;4(6):1159-1165. doi: 10.1182/bloodadvances.2019001165.
Cysteinyl leukotrienes (CysLTs) are lipid mediators of inflammation. In patients with sickle cell disease (SCD), levels of CysLTs are increased compared with controls and associated with a higher rate of hospitalization for pain. We tested the hypothesis that administration of the CysLT receptor antagonist montelukast would improve SCD-related comorbidities, including pain, in adolescents and adults with SCD. In a phase 2 randomized trial, we administered montelukast or placebo for 8 weeks. The primary outcome measure was a >30% reduction in soluble vascular cell adhesion molecule 1 (sVCAM), a marker of vascular injury. Secondary outcome measures were reduction in daily pain, improvement in pulmonary function, and improvement in microvascular blood flow, as measured by laser Doppler velocimetry. Forty-two participants with SCD were randomized to receive montelukast or placebo for 8 weeks. We found no difference between the montelukast and placebo groups with regard to the levels of sVCAM, reported pain, pulmonary function, or microvascular blood flow. Although montelukast is an effective treatment for asthma, we did not find benefit for SCD-related outcomes. This clinical trial was registered at www.clinicaltrials.gov as #NCT01960413.
半胱氨酰白三烯（CysLTs）是炎症的脂质介质。在镰状细胞病（SCD）患者中，与对照组相比，CysLTs水平升高，且与更高的疼痛住院率相关。我们检验了以下假设：给予半胱氨酰白三烯受体拮抗剂孟鲁司特可改善SCD相关的合并症，包括疼痛，该研究针对患有SCD的青少年和成人。在一项2期随机试验中，我们给予孟鲁司特或安慰剂，为期8周。主要结局指标是可溶性血管细胞黏附分子1（sVCAM）降低>30%，sVCAM是血管损伤的一个标志物。次要结局指标包括每日疼痛减轻、肺功能改善以及通过激光多普勒测速仪测量的微血管血流改善。42名SCD参与者被随机分组，接受孟鲁司特或安慰剂治疗8周。我们发现孟鲁司特组和安慰剂组在sVCAM水平、报告的疼痛、肺功能或微血管血流方面没有差异。尽管孟鲁司特是哮喘的有效治疗药物，但我们未发现其对SCD相关结局有益。该临床试验已在www.clinicaltrials.gov上注册，编号为#NCT01960413。
