Clinical trial NCT01247870: Metformin in Chronic Obstructive Pulmonary Disease
Official title: A Randomised, Double-blind, Placebo-controlled Trial of Metformin in Chronic Obstructive Pulmonary Disease (COPD) Exacerbations: a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: Chronic obstructive pulmonary disease, COPD, metformin
Lead sponsor: St George's, University of London
Sponsor class: OTHER
Collaborators: name: Medical Research Council
name: British Lung Foundation
First posted: 2010-11-24
Enrollment: 52
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Capillary glucose concentration
timeFrame: During hospitalisation period
Secondary outcomes:
measure: COPD Assessment Test score
timeFrame: Study entry, hospital discharge, and follow-up
measure: Exacerbation of Chronic Pulmonary Disease Tool (EXACT) score
timeFrame: Days 5, 10 and 28
measure: Time to discharge
timeFrame: Hospital discharge
measure: Recurrent exacerbation, readmission, and death rate
timeFrame: 3 months
measure: Insulin requirement during hospitalisation period
timeFrame: During hospitalisation period following study entry
measure: Haemoglobin A1c
timeFrame: Follow-up (one month post study entry)
measure: C-reactive protein concentration
timeFrame: Days 7 and follow-up (one month)
measure: Body mass index
timeFrame: Follow-up (one month)
measure: Waist circumference
timeFrame: Follow-up (one month)
measure: Forced expiratory volume in 1 second
timeFrame: At hospital discharge and follow-up (one month)
measure: Fructosamine
timeFrame: At hospital discharge and follow-up (one month)
measure: Interleukin 6
timeFrame: At hospital discharge and follow-up (one month)
measure: Interleukin 8
timeFrame: At hospital discharge and follow-up (one month)
measure: Tumor necrosis factor alpha
timeFrame: At hospital discharge and follow-up (one month)
measure: Interferon gamma
timeFrame: At hospital discharge and follow-up (one month)
measure: 8-isoprostane
timeFrame: At hospital discharge and follow-up (one month)
measure: Total carbonyl stress
timeFrame: At hospital discharge and follow-up (one month)
measure: Glutathione reduced vs oxidised
timeFrame: At hospital discharge and follow-up (one month)
Other outcomes:
Locations:
city: Hartlepool
country: United Kingdom
facility: North Tees and Hartlepool NHS Trust
state: Cleveland
city: Lancaster
country: United Kingdom
facility: University Hospitals of Morecambe Bay NHS Trust
state: Cumbria
city: Hastings
country: United Kingdom
facility: East Sussex Healthcare NHS Trust
state: East Sussex
city: Blackpool
country: United Kingdom
facility: Blackpool Teaching Hospitals NHS Trust
state: Lancashire
city: Preston
country: United Kingdom
facility: Lancashire Teaching Hospitals NHS Trust
state: Lancashire
city: Sutton-in-Ashfield
country: United Kingdom
facility: Sherwood Forest Hospitals NHS Trust
state: Nottinghamshire
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital
city: London
country: United Kingdom
facility: St George's Hospital
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
Study officials:
affiliation: St George's, University of London
name: Emma H Baker, MBChB PhD
role: STUDY_CHAIR
affiliation: St George's Healthcare NHS Trust
name: Andrew W Hitchings, BSc MBBS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.