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

当脑内的血管破裂时，会发生SAH；在英国，每年有多达6000人受到影响。它通常是由于血管壁的弱化（动脉瘤），并且可以在没有警告的情况下发生。在所有SAH患者中，有多达一半的患者无法存活到接受医院治疗。在那些存活下来的病人中，流向大脑的血流量可能会减少，因为出血的血液刺激了大脑动脉的外表面，导致它们痉挛和变窄。血流量减少会阻止氧气到达脑细胞，导致脑细胞死亡。这被称为脑缺血（CI），导致患者出现类似中风的症状。然而，这些症状可能不会立即显现，因为它们通常在初次出血后3-15天之间出现。这被称为迟发性脑缺血（DCI）。一种叫做白细胞介素-1 （IL-1）的蛋白质是脑损伤后发生损伤的重要触发因素。在SAH之后，IL-1会导致其他蛋白质的释放，从而在循环和大脑中引起炎症。IL-1可以被我们体内天然存在的另一种蛋白质阻断、限制甚至逆转；白细胞介素1受体拮抗剂（IL-1RA）。公司有重复的IL-1RA；作为类风湿性关节炎（Kineret?）的抗炎药物进行营销。我们小组已经成功地测试了Kineret？发现在CI发作时给予高剂量；它能减少炎症和缺血。由于SAH的缺血延迟，可能会给予Kineret？作为一种预防措施而不是治疗；允许使用更小的剂量。我们想确定注射Kineret？少量给予，可减少脑血管炎症和随后的DCI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）招募140名SAH患者，时间超过2个月。年。患者将由独立的第三方随机分配，接受Kineret？或者在出血后的21天内每天注射两次安慰剂。我们将在预先确定的时间点进行一些评估和血液检查。患者将继续接受SAH的标准治疗，参与本研究不会影响或延迟这种治疗。在整个研究过程中，我们将在以往工作的基础上，与患者-公众参与小组进行磋商，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.