A Randomised, Double-blind, Placebo-controlled Trial of Metformin in Chronic Obstructive Pulmonary Disease (COPD) Exacerbations: a Pilot Study
Overview
- Phase
- Phase 4
- Intervention
- Metformin
- Conditions
- Chronic Obstructive Pulmonary Disease
- Sponsor
- St George's, University of London
- Enrollment
- 52
- Locations
- 9
- Primary Endpoint
- Capillary glucose concentration
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The purpose of this study is to determine the effect of a tablet medication, called metformin, in flare-ups (exacerbations) of chronic obstructive pulmonary disease. The investigators believe that metformin may effectively control the blood sugar level during COPD exacerbations. This is important because there is evidence that a high blood sugar level during exacerbations may be linked with a worse prognosis. The investigators also think that metformin may have other potentially useful effects on inflammation, antioxidant levels, the effectiveness of steroid treatment, and recovery.
Detailed Description
Does metformin lower the blood sugar level in patients suffering from exacerbations of chronic obstructive pulmonary disease (COPD)? COPD is the fourth leading cause of death worldwide, and a major cause of ill health. In the UK, it affects some 3.7 million people and causes over 30,000 deaths per year. It is usually, but not always, caused by smoking. Most people affected are over 65-years-old. Sufferers experience progressively worsening cough, sputum production, breathlessness and exercise limitation. This is punctuated by 'flare-ups' (exacerbations), when their symptoms worsen substantially. Approximately 25% of patients hospitalised for exacerbations die within a year, and over 50% within 5 years. There is a pressing need for new and improved treatments for COPD exacerbations. This study will assess the effect of metformin, a tablet medication, in COPD exacerbations. Metformin has been in common use for over 50 years in patients with diabetes, to lower the blood sugar level. In COPD exacerbations, the blood sugar level is often high, and the higher it is, the more likely the patient will have a poor outcome. This led us to speculate that lowering the sugar level with metformin may improve outcomes from COPD exacerbations. However, COPD and diabetes are quite different diseases, and the investigators do not know whether metformin will work as a sugar-lowering medicine in COPD exacerbations. The investigators need to confirm this before the investigators can perform larger studies to assess its effect on outcomes such as readmission and mortality rates. The investigators will test this medicine in a 1-month trial in patients hospitalised for COPD exacerbations. The target sample size is 69 patients, with a minimum of 48 patients required for primary endpoint analysis. Two-thirds of the patients will take metformin, and one-third a dummy (placebo) tablet. Neither the patients nor the researchers know who is taking which. The investigators will measure their sugar levels by regular finger-prick tests, and then compare the average readings in the two groups. The investigators will also assess the medicine's effects on other markers of blood sugar level, and carry out additional exploratory investigations on the effect of the medicine on clinical outcomes, markers of inflammation, and markers of oxidative/carbonyl stress and steroid responsiveness.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of COPD
- •Hospitalisation for exacerbation of COPD
- •Age ≥35 years
- •Expected to remain in hospital for at least 48 hours
Exclusion Criteria
- •Prior diagnosis of diabetes mellitus requiring insulin or oral hypoglycaemic therapy
- •Hypersensitivity to metformin hydrochloride or to any of the excipients
- •Renal impairment
- •Severe sepsis
- •Metabolic acidosis
- •Decompensated type 2 respiratory failure
- •Severe congestive cardiac failure
- •Acute coronary syndrome
- •Hepatic insufficiency
- •Excessive alcohol consumption
Arms & Interventions
Metformin
Metformin 1 g twice daily for 28-35 days
Intervention: Metformin
Placebo
Matched placebo capsules
Intervention: Placebo
Outcomes
Primary Outcomes
Capillary glucose concentration
Time Frame: During hospitalisation period
The mean capillary glucose concentration during hospitalisation period following study entry, as a measure of both efficacy and safety.
Secondary Outcomes
- Fructosamine(At hospital discharge and follow-up (one month))
- Exacerbation of Chronic Pulmonary Disease Tool (EXACT) score(Days 5, 10 and 28)
- Haemoglobin A1c(Follow-up (one month post study entry))
- C-reactive protein concentration(Days 7 and follow-up (one month))
- Body mass index(Follow-up (one month))
- Waist circumference(Follow-up (one month))
- Interleukin 8(At hospital discharge and follow-up (one month))
- Tumor necrosis factor alpha(At hospital discharge and follow-up (one month))
- Insulin requirement during hospitalisation period(During hospitalisation period following study entry)
- COPD Assessment Test score(Study entry, hospital discharge, and follow-up)
- Time to discharge(Hospital discharge)
- Recurrent exacerbation, readmission, and death rate(3 months)
- Forced expiratory volume in 1 second(At hospital discharge and follow-up (one month))
- Interleukin 6(At hospital discharge and follow-up (one month))
- Interferon gamma(At hospital discharge and follow-up (one month))
- 8-isoprostane(At hospital discharge and follow-up (one month))
- Total carbonyl stress(At hospital discharge and follow-up (one month))
- Glutathione reduced vs oxidised(At hospital discharge and follow-up (one month))