Developmental Clinical Studies - A clinical trial of metformin in COPD exacerbations

慢性阻塞性肺疾病(COPD)是一种通常由吸烟引起的肺部疾病。慢性阻塞性肺病患者会感到呼吸急促，并有慢性咳嗽。病情不断恶化，限制了运动和正常活动。这些症状是由将空气输送到肺部的呼吸管和氧气从空气进入血液的气囊受损引起的。在英国，慢性阻塞性肺病影响着大约370万人，每年导致超过3万人死亡。慢性阻塞性肺疾病是世界上第四大常见死因。慢性阻塞性肺病患者时不时会发作，感觉更喘不过气来或咳出更多痰(痰)。这些发作被称为病情加重，通常由感染引发。病情恶化是慢性阻塞性肺疾病患者的主要事件。在病情恶化期间，COPD患者需要更多的治疗，并可能需要入院治疗。病情恶化可能需要数周时间才能完全恢复，有些人永远也无法恢复到病情恶化前的状态。不幸的是，尽管目前是最好的治疗方法，但许多人在病情恶化后的几周、几个月甚至几年内死亡。需要新的治疗方法来预防死亡和加速病情恶化后的恢复。目的我们研究的总体目标是看看一种名为二甲双胍的药物是否可以帮助COPD患者在病情恶化后更快地恢复或存活更长时间。二甲双胍通常用于降低糖尿病患者的血糖。我们发现，大多数因COPD加重而住院的患者都有高血糖。他们的血糖越高，他们从病情恶化中恢复的情况就越差。因此，我们认为在慢性阻塞性肺疾病急性加重期使用二甲双胍降低血糖可以促进康复。二甲双胍还可以抑制炎症，清除被称为自由基的有害物质。这些效应对COPD恶化患者可能是有益的。为了验证我们的理论，我们回顾了COPD患者的医院记录。我们发现，服用二甲双胍出院的患者比没有服用二甲双胍的患者存活时间更长。这一发现令人鼓舞，但必须谨慎解读，因为有几种可能的解释。我们现在需要在临床试验中测试二甲双胍的益处。住院的COPD恶化患者将被邀请参加试验。那些同意的人将接受COPD恶化的所有常规治疗。此外，他们还将以胶囊的形式进行学习治疗，每天两次，为期一个月。参与者将随机分配(随机)服用二甲双胍或不服用药物(安慰剂)。我们和参与者都不知道谁在服用什么。这将使我们能够对二甲双胍的疗效做出公正的评估。我们将通过比较住院患者和整个研究期间的血糖，使用一种名为果糖胺的测试来评估二甲双胍的益处。我们将检查服用二甲双胍的人是否会变得更加不适或产生危险的副作用，以及他们是否能够耐受这些药片。我们还将了解二甲双胍是否有助于他们更快地从COPD恶化中恢复过来。然而，这将需要在未来更多的患者中进行更彻底的测试。潜在的BENEFIT在这项试验结束时，我们将知道二甲双胍是否可以安全地降低COPD恶化患者的血糖。下一步将是在更多的COPD患者身上测试二甲双胍，看看它是否可以帮助他们更快地从病情恶化中恢复过来。二甲双胍价格便宜，而且随处可得。如果它有效，它可能很快就会被采用为这些患者的一种新疗法。

CONTEXTChronic obstructive pulmonary disease (COPD) is a lung disease that is usually caused by smoking. People with COPD feel short of breath and have a chronic cough. The condition worsens steadily, limiting exercise and normal activities. These symptoms are caused by damage to the breathing tubes which carry air into the lungs and to the air sacs where oxygen crosses from the air into the blood. In the UK, COPD affects around 3.7 million people and causes over 30,000 deaths per year. It is the fourth most common cause of death worldwide.From time to time, COPD patients experience attacks, where they feel more breathless or cough up more phlegm (sputum). These attacks are called exacerbations and are often set off by infection. Exacerbations are major events for people with COPD. During an exacerbation, COPD patients need more treatment and may require admission to hospital. It can take weeks to recover fully from an exacerbation and some people never get back to how they were before the exacerbation. Unfortunately, despite current best treatment, many people die during the weeks, months and years after an exacerbation. New treatments are required to prevent deaths and speed up recovery after exacerbations.AIMThe overall aim of our research is to see whether a drug called metformin can help COPD patients recover more quickly or survive longer after an exacerbation.Metformin is usually used to lower blood sugar in patients with diabetes. We have found that most patients admitted to hospital for COPD exacerbations have high blood sugar. The higher their blood sugar, the less well they recover from their exacerbation. We therefore think that using metformin to lower blood sugar in COPD patients during exacerbations could improve recovery. Metformin can also dampen down inflammation and mop-up harmful substances called free radicals. These effects could be beneficial for COPD patients with exacerbations. To test our theory we looked back at hospital records of COPD patients. We found that patients leaving hospital on metformin survived longer than those without metformin. This finding is encouraging, but must be interpreted cautiously, as there are several possible explanations. We now need to test the benefits of metformin in clinical trials.THE STUDYPatients admitted to hospital with COPD exacerbations will be invited to take part in the trial. Those who agree will receive all the usual treatments for COPD exacerbations. In addition, they will take a study treatment as a capsule twice daily for 1 month. Participants will be allocated by chance (randomisation) to receive metformin or no medicine (placebo) in the capsule. Neither we nor the participants will know who is taking what. This will allow us to make an unbiased assessment of the effects of metformin.We will assess the benefits of metformin by comparing blood glucose between patients during hospital admission and over the whole study using a test called fructosamine. We will check that people taking metformin don't become more unwell or develop dangerous side effects and that they can tolerate the tablets. We will also get some idea of whether metformin helps them recover more quickly from their COPD exacerbations. However this will need to be tested more thoroughly in the future in a larger group of patients.POTENTIAL BENEFITSAt the end of this trial we will know whether metformin can lower blood sugar safely in patients with COPD exacerbations. The next step will be to test metformin in a larger number of COPD patients to see if it can help them to recover more quickly from their exacerbations. Metformin is cheap and widely available. If it works it could quickly be adopted as a new treatment for these patients.