Pauls Mathilde M H, Clarke Natasha, Trippier Sarah, Betteridge Shai, Howe Franklyn A, Khan Usman, Kruuse Christina, Madigan Jeremy B, Moynihan Barry, Pereira Anthony C, Rolfe Debbie, Rostrup Egill, Haig Caroline E, Barrick Thomas R, Isaacs Jeremy D, Hainsworth Atticus H
Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, Cranmer Terrace, London, SW17 0RE, UK.
Cell Biology and Genetics Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, Cranmer Terrace, London, SW17 0RE, UK.
Trials. 2017 May 22;18(1):229. doi: 10.1186/s13063-017-1973-9.
Cerebral small vessel disease is a common cause of vascular cognitive impairment in older people, with no licensed treatment. Cerebral blood flow is reduced in small vessel disease. Tadalafil is a widely prescribed phosphodiesterase-5 inhibitor that increases blood flow in other vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease.
METHODS/DESIGN: Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo.
54 participants are required to detect a 15% increase in cerebral blood flow in subcortical white matter (p < 0.05, 90% power). Primary outcomes are cerebral blood flow in subcortical white matter and deep grey nuclei. Secondary outcomes are cortical grey matter cerebral blood flow and performance on cognitive tests (reaction time, information processing speed, digit span forwards and backwards, semantic fluency).
Recruitment started on 4th September 2015 and 36 participants have completed to date (19th April 2017). No serious adverse events have occurred. All participants have been recruited from one centre, St George's University Hospitals NHS Foundation Trust.
European Union Clinical Trials Register: EudraCT number 2015-001235-20 . Registered on 13 May 2015.
脑小血管病是老年人血管性认知障碍的常见病因，目前尚无获批的治疗方法。脑小血管病患者的脑血流量会减少。他达拉非是一种广泛应用的磷酸二酯酶-5抑制剂，可增加其他血管区域的血流量。本试验的目的是检验他达拉非可增加脑小血管病老年人脑血流量这一假设。
方法/设计：小血管病单次服用他达拉非后的动脉自旋标记灌注试验（PASTIS）是一项II期随机双盲交叉试验。在间隔7 - 30天的两次访视中，参与者在口服他达拉非（20毫克）或安慰剂给药前和给药后接受动脉自旋标记以测量脑血流量，并进行一系列认知测试。
需要54名参与者来检测皮质下白质脑血流量增加15%（p < 0.05，检验效能90%）。主要结局是皮质下白质和深部灰质核团的脑血流量。次要结局是皮质灰质脑血流量和认知测试表现（反应时间、信息处理速度、顺背和倒背数字广度、语义流畅性）。
招募工作于2015年9月4日开始，截至2017年4月19日已有36名参与者完成试验。未发生严重不良事件。所有参与者均从圣乔治大学医院国民保健服务基金会信托这一中心招募。
欧盟临床试验注册库：EudraCT编号2015 - 001235 - 20。于2015年5月13日注册。
