Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia

孟鲁司特治疗镰状细胞性贫血的 2 期研究

• 批准号: 9405682
• 负责人: Michael R. DeBaun
• 金额: $ 63.26万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9405682
• 关键词: Phase; Study; Montelukast; Treatment; Sickle

DESCRIPTION (provided by applicant): This proposal is for a randomized, double-blind, placebo-controlled Phase 2 trial of montelukast (a cysteinyl leukotriene receptor 1 antagonist) combined with hydroxyurea (HU) for the prevention of vaso-occlusive pain episodes in adolescents and adults with sickle cell disease (SCD). The investigative team has generated clinical and pre-clinical data implicating cysteinyl leukotrienes (CysLTs) in the pathogenesis of vaso-occlusion. In separate cohorts of children and adults with SCD, baseline levels of CysLTs were associated with the rate of hospitalizations for pain. Further, murine models of SCD treated with montelukast showed decreased vascular congestion and lower levels of the inflammatory marker soluble vascular cell adhesion molecule-1 (sVCAM-1) compared to untreated SCD mice. Montelukast is an FDA-approved therapy that is already used in individuals with SCD who also have asthma. The hypothesis to be tested is that montelukast adds efficacy to HU therapy for improving vaso-occlusion when compared to HU alone. In this proposal, participants treated with montelukast and HU will be compared to those treated with placebo and HU for a total of 8 weeks. The following specific aims will be tested in adolescents and adults with SCD: Aim 1. To determine whether montelukast versus placebo added to HU will improve markers of vaso-occlusion-associated tissue injury in adolescents and adults with SCD, and Aim 2. To evaluate physiologic effects of montelukast versus placebo added to HU in adolescents and adults with SCD, specifically (Subaim 2A) to determine if montelukast versus placebo added to HU will improve lung function in adolescents and adults with SC; (Subaim 2B) to determine if montelukast versus placebo added to HU will improve forearm microvascular blood flow in adolescents and adults with SCD, respectively. Anticipating a 20 percent dropout rate, 63 participants will be enrolled with the expectation that 50 participants will receive montelukast or placebo therapy for 8 weeks.

描述（由申请人提供）： 该提议是针对蒙特鲁卡斯特（CySteinyl Leukotriene受体1拮抗剂）的随机，双盲，安慰剂对照的2期试验，结合了羟基脲（HU），用于预防青少年和成人小镰状细胞病（SCD）的血管核酸止痛事件（SCD）。调查小组已经产生了临床和临床前数据，这涉及白细胞三烯（CYSLT）在血管封闭的发病机理中。在单独的患有SCD的儿童和成人同类中，基线水平的Cyslt水平与住院治疗率有关。此外，与未处理的SCD小鼠相比，用Montelukast处理的SCD的鼠模型显示出降低的血管充血和炎症标记可溶性血管细胞粘附分子1（SVCAM-1）的降低。 Montelukast是一种由FDA批准的疗法，已经用于患有哮喘的SCD患者。 要检验的假设是，与单独使用HU相比，Montelukast增加了HU疗法改善血管含量的功效。 在此提案中，将接受Montelukast和HU治疗的参与者与安慰剂和HU治疗的参与者总计8周。 The following specific aims will be tested in adolescents and adults with SCD: Aim 1. To determine whether montelukast versus placebo added to HU will improve markers of vaso-occlusion-associated tissue injury in adolescents and adults with SCD, and Aim 2. To evaluate physiologic effects of montelukast versus placebo added to HU in adolescents and adults with SCD, specifically (Subaim 2A) to确定在HU中添加的Montelukast和安慰剂是否会改善SC的青少年和成年人的肺功能； （Subaim 2b）确定在HU中添加的Montelukast和安慰剂是否会分别改善SCD的青少年和成年人的前臂微血管血流。预计将有20％的辍学率，有63名参与者将被招募，希望有50名参与者将在8周内接受Montelukast或安慰剂疗法。