Metformin in Chronic Obstructive Pulmonary Disease

NCT ID: NCT01247870

Last Updated: 2015-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2014-05-31

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.

Conditions

Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Metformin

Metformin 1 g twice daily for 28-35 days

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Metformin 1 g twice daily for 28-35 days

Placebo

Matched placebo capsules

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Metformin

Metformin 1 g twice daily for 28-35 days

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

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
• 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

• Minimum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical Research Council

OTHER_GOV

Sponsor Role: collaborator

British Lung Foundation

OTHER

Sponsor Role: collaborator

St George's, University of London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emma H Baker, MBChB PhD

Role: STUDY_CHAIR

St George's, University of London

Andrew W Hitchings, BSc MBBS

Role: PRINCIPAL_INVESTIGATOR

St George's Healthcare NHS Trust

Locations

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

St George's Hospital

London, , United Kingdom

Freeman Hospital

Newcastle, , United Kingdom

Countries

United Kingdom

References

Hitchings AW, Baker EH, Jones PW. Handling missing items in the Exacerbations of Chronic Pulmonary Disease Tool. Eur Respir J. 2016 Aug;48(2):564-6. doi: 10.1183/13993003.00269-2016. Epub 2016 May 12. No abstract available.

Reference Type: DERIVED

PMID: 27174882 (View on PubMed)

Hitchings AW, Lai D, Jones PW, Baker EH; Metformin in COPD Trial Team. Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial. Thorax. 2016 Jul;71(7):587-93. doi: 10.1136/thoraxjnl-2015-208035. Epub 2016 Feb 25.

Reference Type: DERIVED

PMID: 26917577 (View on PubMed)

Other Identifiers

2010-020818-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

10.0086

Identifier Type: -

Identifier Source: org_study_id