Developmental Clinical Studies - Does subcutaneous IL-1RA reduce inflammation following subarachnoid haemorrhage?

当大脑中的血管破裂时，就会发生SAH；在英国，每年有多达6000人受到影响。这通常是由于血管壁变弱(动脉瘤)，并可在没有征兆的情况下发生。多达一半患有SAH的患者无法存活足够长的时间接受医院治疗。在那些幸存下来的人中，流向大脑的血液可能会减少，因为出血的血液刺激了脑动脉的外表面，导致它们痉挛和变窄。血流量的减少会阻止氧气进入脑细胞，导致脑细胞死亡。这被称为脑缺血(CI)，会导致患者经历类似中风的症状。然而，这些症状可能不会立即显现，因为它们通常发生在最初出血后3-15天。这就是所谓的迟发性脑缺血(DCI)。一种名为白介素1(IL-1)的蛋白质是脑梗塞后损伤发生的重要触发因素。在SAH后，IL-1会导致其他蛋白质的释放，从而导致循环和大脑的炎症。IL-1可以被体内天然存在的另一种蛋白质--白介素1受体拮抗剂(IL-1RA)所阻断、限制甚至逆转。一家公司复制了IL-1RA；将其作为类风湿性关节炎的抗炎疗法(Kineet？)进行营销。我们的团队已经成功测试了Kineet？研究发现，当在脑梗塞开始时给予高剂量的药物时，它可以减少炎症和缺血。由于SAH中的缺血被延迟，有可能给Kineet？作为预防措施而不是治疗；允许使用较小的剂量。我们想要确定注射少量的Kineet？是否可以减少脑血管炎症和随后的DCI的发生率。为此，我们将从我们的神经外科中心(索尔福德皇家NHS基金会信托基金)招募多达140名SAH患者。好几年了。患者将由独立的第三方随机接受Kineet？或安慰剂，在出血后每天注射两次，最多21天。我们将在预定的时间点进行多次评估和血液测试。患者将继续接受SAH的标准护理，参与这项研究不会影响或推迟这种护理。在整个研究过程中，我们将咨询患者-公众参与团体，在以前工作的基础上发展，并加强我们与非专业社区的关系。

SAH occurs when a blood vessel within the brain bursts; affecting up to 6,000 people every year in the UK. It is often due to a weakening in the blood vessel wall (aneurysm) and can occur without warning. Up to half of all patients who have a SAH do not survive long enough to receive hospital treatment. Of those who survive, blood flow to the brain may be reduced due to blood from the haemorrhage irritating the outer surface of brain arteries causing them to spasm and become narrower. Reduction in blood flow prevents oxygen reaching brain cells causing them to die. This is known as cerebral ischaemia (CI) and causes patients to experience symptoms similar to a stroke. However, these symptoms may not be immediately apparent as they commonly occur between 3-15 days after the initial haemorrhage. This is known as Delayed Cerebral Ischaemia (DCI).A protein called interleukin-1 (IL-1) is an important trigger for damage happening after CI. After SAH, IL-1 causes the release of other proteins which cause inflammation in the circulation and the brain. IL-1 can be blocked, limited or even reversed by another protein present naturally in our body; interleukin-1 receptor antagonist (IL-1RA). A company has duplicated IL-1RA; marketing it as an anti-inflammatory treatment for rheumatoid arthritis (Kineret?). Our group has successfully tested Kineret? and found that when given in high doses at the onset of CI; it reduces inflammation and ischaemia. As ischaemia in SAH is delayed, it may be possible to give Kineret? as a preventative measure rather than a treatment; allowing smaller doses to be used. We want to establish whether injections of Kineret?, given in small amounts, reduces inflammation in brain blood vessels and the subsequent incidence of DCI. To do this, we will recruit up to 140 SAH patients from our neurosurgical centre (Salford Royal NHS Foundation Trust) over 2? years. Patients will be randomised by an independent third party to receive either Kineret? or placebo in twice daily injections for up to 21 days after the bleed. We will perform a number of assessments and blood tests at pre-determined time points. Patients will continue to receive the standard care for SAH and participation in this study will not affect or delay this care. Throughout the study we will consult with Patient-Public Involvement groups, building on previous work and strengthening our relationship with the lay community.