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

慢性阻塞性肺疾病（COPD）是一种肺部疾病，通常由吸烟引起。COPD患者感觉呼吸急促，并有慢性咳嗽。病情稳定，限制了运动和正常活动。这些症状是由将空气带入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，COPD影响约370万人，每年导致超过30，000人死亡。慢性阻塞性肺疾病是世界上第四大常见的死亡原因。慢性阻塞性肺疾病患者会不时发作，感到呼吸困难或咳出更多痰。这些发作被称为急性加重，通常由感染引起。急性加重是COPD患者的主要事件。在急性加重期间，COPD患者需要更多的治疗，并可能需要住院。它可能需要几个星期才能从恶化中完全恢复，有些人永远不会回到恶化前的状态。不幸的是，尽管目前最好的治疗，许多人在恶化后的几周，几个月和几年内死亡。需要新的治疗方法来预防死亡和加速加重后的恢复。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患者在加重后更快地恢复或生存更长时间。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急性加重而入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得越差。因此，我们认为在COPD患者急性加重期使用二甲双胍降低血糖可以改善恢复。蛋氨酸还可以抑制炎症，清除被称为自由基的有害物质。这些作用可能对COPD急性加重患者有益。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，出院时服用二甲双胍的患者比未服用二甲双胍的患者生存时间更长。这一发现令人鼓舞，但必须谨慎解释，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。同意的患者将接受COPD急性加重的所有常规治疗。此外，他们将接受研究治疗胶囊，每日两次，持续1个月。受试者将随机分配（随机化）接受二甲双胍或胶囊中无药物（安慰剂）。我们和参与者都不知道谁在拿什么。这将使我们能够对二甲双胍的作用进行无偏倚的评估。我们将通过使用果糖胺测试比较患者入院期间和整个研究期间的血糖来评估二甲双胍的益处。我们将检查服用二甲双胍的人不会变得更加不适或产生危险的副作用，并且他们可以耐受片剂。我们还将了解二甲双胍是否有助于他们更快地从COPD加重中恢复。然而，这将需要在未来更大的患者群体中进行更彻底的测试。潜在的益处在本试验结束时，我们将知道二甲双胍是否可以安全地降低COPD急性加重患者的血糖。下一步将是在更多的COPD患者中测试二甲双胍，看看它是否可以帮助他们更快地从病情加重中恢复过来。甲硫氨酸价格便宜，而且随处可得。如果它有效，它可以很快被采用作为这些患者的新治疗方法。

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.