Department of Cardiology, Maastricht University Medical Center+ and CARIM, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands.
Department of Clinical Chemistry, Maastricht University Medical Center+, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands.
Nutrients. 2018 Mar 21;10(4):386. doi: 10.3390/nu10040386.
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-sodiumfluoride (F-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-NaF PET/MR after 6 months and CT after 6 and 18 months. The primary endpoint is the change in PET/MR F-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).
BASIK2 是一项前瞻性、双盲、随机安慰剂对照试验,旨在研究维生素 K2(甲萘醌-7;MK7)对二叶式主动脉瓣(BAV)和钙化性主动脉瓣狭窄(CAVS)中钙化成像测量的影响。BAV 与 CAVS 的早期发展有关。病理生理机制尚未完全明确,唯一的治疗方法是在进展为严重症状性狭窄时进行瓣膜置换。推测基质 Gla 蛋白(MGP)失活参与了进展过程。由于 MGP 是一种维生素 K 依赖性蛋白,MK7 的补充是激活 MGP 并干预 CAVS 进展的一种药理学选择。该研究将纳入 44 例 BAV 合并轻中度 CAVS 患者,基线 F-锝氟化物(F-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,患者将被随机(1:1)分为 MK7(360 mcg/天)或安慰剂组。在 18 个月的随访期间,患者每 6 个月到医院就诊,在 6 个月后进行第二次 F-NaF PET/MR,在 6 个月和 18 个月后进行 CT。主要终点是与安慰剂组相比,PET/MR F-NaF 摄取(6 个月减去基线)的变化。主要次要终点是钙评分(CT)的变化、左心室重构反应的进展和 CAVS 严重程度(超声心动图)。我们还将检查早期钙化活性(PET)与后期钙评分(CT)变化之间的相关性。
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