Metformin in Chronic Obstructive Pulmonary Disease

Phase 4

Completed

• Conditions: Chronic Obstructive Pulmonary Disease
• Interventions: Drug: Placebo; Drug: Metformin

• Registration Number: NCT01247870
• Lead Sponsor: St George's, University of London

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2010-11-23
• Study First Submitted QC: 2010-11-23
• Study First Posted: 2010-11-24
• Study Start: 2011-01
• Primary Completion: 2014-03
• Study Completion: 2014-05
• Status Verified: 2015-05
• Last Update Submitted: 2015-05-06
• Last Update Posted: 2015-05-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

• Diagnosis of COPD
• Hospitalisation for exacerbation of COPD
• Age ≥35 years
• Expected to remain in hospital for at least 48 hours

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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
• Malnourished or at high risk for malnutrition
• Moribund or not for active treatment
• Admitted to critical care unit
• Unable to give informed consent
• Pregnancy or lactation

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matched placebo capsules
Metformin	Metformin	Metformin 1 g twice daily for 28-35 days

Primary Outcome Measures

Name	Time	Method
Capillary glucose concentration	During hospitalisation period	The mean capillary glucose concentration during hospitalisation period following study entry, as a measure of both efficacy and safety.

Secondary Outcome Measures

Name	Time	Method
Body mass index	Follow-up (one month)
Waist circumference	Follow-up (one month)
Fructosamine	At hospital discharge and follow-up (one month)	Mean serum fructosamine concentration
C-reactive protein concentration	Days 7 and follow-up (one month)	Mean concentration of C-reactive protein in the blood
Exacerbation of Chronic Pulmonary Disease Tool (EXACT) score	Days 5, 10 and 28
Haemoglobin A1c	Follow-up (one month post study entry)	Mean haemoglobin A1c concentration
Interleukin 8	At hospital discharge and follow-up (one month)	Serum concentration of IL-8 (absolute value and change from baseline)
Tumor necrosis factor alpha	At hospital discharge and follow-up (one month)	Serum concentration of TNF-alpha (absolute value and change from baseline)
COPD Assessment Test score	Study entry, hospital discharge, and follow-up
Time to discharge	Hospital discharge	Number of days from hospital admission to hospital discharge
Insulin requirement during hospitalisation period	During hospitalisation period following study entry	Mean daily insulin use during hospitalisation period following study entry
Recurrent exacerbation, readmission, and death rate	3 months	Rates of recurrent exacerbation (defined as treatment with antibiotics and/or systemic corticosteroids for breathlessness, cough or wheeze), readmission to hospital, or death
Forced expiratory volume in 1 second	At hospital discharge and follow-up (one month)	Mean forced expiratory volume in 1 second (FEV1) expressed as a percentage of predicted value
Interleukin 6	At hospital discharge and follow-up (one month)	Serum concentration of IL-6 (absolute value and change from baseline)
Interferon gamma	At hospital discharge and follow-up (one month)	Serum concentration of IFN-gamma (absolute value and change from baseline)
8-isoprostane	At hospital discharge and follow-up (one month)	Serum concentration of 8-isoprostane (absolute value and change from baseline)
Total carbonyl stress	At hospital discharge and follow-up (one month)	Total carbonyl stress, measured in serum (absolute value and change from baseline)
Glutathione reduced vs oxidised	At hospital discharge and follow-up (one month)	Glutathione reduced vs oxidised, measured in serum (absolute value and change from baseline)

Trial Locations

Locations (9)

North Tees and Hartlepool NHS Trust; 🇬🇧 Hartlepool, Cleveland, United Kingdom

University Hospitals of Morecambe Bay NHS Trust; 🇬🇧 Lancaster, Cumbria, United Kingdom

East Sussex Healthcare NHS Trust; 🇬🇧 Hastings, East Sussex, United Kingdom

Blackpool Teaching Hospitals NHS Trust; 🇬🇧 Blackpool, Lancashire, United Kingdom

Lancashire Teaching Hospitals NHS Trust; 🇬🇧 Preston, Lancashire, United Kingdom

Sherwood Forest Hospitals NHS Trust; 🇬🇧 Sutton-in-Ashfield, Nottinghamshire, United Kingdom

Chelsea and Westminster Hospital; 🇬🇧 London, United Kingdom

Freeman Hospital; 🇬🇧 Newcastle, United Kingdom

St George's Hospital; 🇬🇧 London, United Kingdom