Bicuspid Aortic Valve Stenosis and the Effect of Vitamin K2 on Calcification Using 18F-Sodium Fluoride Positron Emission Tomography/Magnetic Resonance: The BASIK2 Rationale and Trial Design
Bicuspid Aortic Valve Stenosis and the Effect of Vitamin K2 on Calcification Using 18F-Sodium Fluoride Positron Emission Tomography/Magnetic Resonance: The BASIK2 Rationale and Trial Design
复制标题
DOI：
10.3390/nu10040386
复制
发表时间：
2018-04-01
期刊：
影响因子：
5.9
通讯作者：
Kietselaer, Bas L. J. H.
中科院分区：
文献类型：
--
作者：
Peeters, Frederique E. C. M.;van Mourik, Manouk J. W.;Kietselaer, Bas L. J. H.
BASIK2 是一项前瞻性、双盲、随机安慰剂对照试验，研究维生素 K2（menaquinone-7；MK7）对二叶式主动脉瓣 (BAV) 钙化和钙化性主动脉瓣狭窄 (CAVS) 成像测量的影响。 BAV 与 CAVS 的早期发展相关。病理生理机制尚未完全确定，唯一可用的治疗方法是进展为严重症状性狭窄时进行瓣膜置换。基质 Gla 蛋白 (MGP) 失活被认为与进展有关。作为一种维生素 K 依赖性蛋白质，补充 MK7 是激活 MGP 和干预 CAVS 进展的一种药理学选择。该研究将包括 44 名患有 BAV 和轻中度 CAVS 的受试者，并将进行基线 F-18-氟化钠 (F-18-NaF) 正电子发射断层扫描 (PET)/磁共振 (MR) 和计算机断层扫描 (CT) 评估。此后，受试者将被随机 (1:1) 接受 MK7（360 微克/天）或安慰剂。在 18 个月的随访期间，受试者每 6 个月去医院一次，在 6 个月后接受第二次 F-18-NaF PET/MR，并在 6 个月和 18 个月后接受 CT。主要终点是与安慰剂组中的增量变化相比，PET/MR F-18-NaF 摄取的变化（6 个月减去基线）。主要的次要终点是钙评分 (CT) 的变化、左心室重塑反应的进展和 CAVS 严重程度（超声心动图）。我们还将检查早期钙化活动 (PET) 与后期钙评分 (CT) 变化之间的关联。
BASIK2 is a prospective, double-blind, randomized placebo-controlled trial investigating the effect of vitamin K2 (menaquinone-7;MK7) on imaging measurements of calcification in the bicuspid aortic valve (BAV) and calcific aortic valve stenosis (CAVS). BAV is associated with early development of CAVS. Pathophysiologic mechanisms are incompletely defined, and the only treatment available is valve replacement upon progression to severe symptomatic stenosis. Matrix Gla protein (MGP) inactivity is suggested to be involved in progression. Being a vitamin K dependent protein, supplementation with MK7 is a pharmacological option for activating MGP and intervening in the progression of CAVS. Forty-four subjects with BAV and mild-moderate CAVS will be included in the study, and baseline F-18-sodiumfluoride (F-18-NaF) positron emission tomography (PET)/ magnetic resonance (MR) and computed tomography (CT) assessments will be performed. Thereafter, subjects will be randomized (1:1) to MK7 (360 mcg/day) or placebo. During an 18-month follow-up period, subjects will visit the hospital every 6 months, undergoing a second F-18-NaF PET/MR after 6 months and CT after 6 and 18 months. The primary endpoint is the change in PET/MR F-18-NaF uptake (6 months minus baseline) compared to this delta change in the placebo arm. The main secondary endpoints are changes in calcium score (CT), progression of the left ventricularremodeling response and CAVS severity (echocardiography). We will also examine the association between early calcification activity (PET) and later changes in calcium score (CT).