Metformin in Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

A Randomised, Double-blind, Placebo-controlled Trial of Metformin in Chronic Obstructive Pulmonary Disease (COPD) Exacerbations: a Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01247870
• Other study ID #: 10.0086
• Secondary ID: 2010-020818-28
• Status: Completed
• Phase: Phase 4
• First received: November 23, 2010
• Last updated: May 6, 2015
• Start date: January 2011
• Est. completion date: May 2014

Study information

• Verified date: May 2015
• Source: St George's, University of London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics CommitteeUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: May 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Metformin
Metformin 1 g twice daily for 28-35 days
• Placebo
Placebo

Locations

Country	Name	City	State
United Kingdom	Blackpool Teaching Hospitals NHS Trust	Blackpool	Lancashire
United Kingdom	North Tees and Hartlepool NHS Trust	Hartlepool	Cleveland
United Kingdom	East Sussex Healthcare NHS Trust	Hastings	East Sussex
United Kingdom	University Hospitals of Morecambe Bay NHS Trust	Lancaster	Cumbria
United Kingdom	Chelsea and Westminster Hospital	London
United Kingdom	St George's Hospital	London
United Kingdom	Freeman Hospital	Newcastle
United Kingdom	Lancashire Teaching Hospitals NHS Trust	Preston	Lancashire
United Kingdom	Sherwood Forest Hospitals NHS Trust	Sutton-in-Ashfield	Nottinghamshire

Sponsors (3)

Lead Sponsor	Collaborator
St George's, University of London	British Lung Foundation, Medical Research Council

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Capillary glucose concentration	The mean capillary glucose concentration during hospitalisation period following study entry, as a measure of both efficacy and safety.	During hospitalisation period	Yes
Secondary	COPD Assessment Test score		Study entry, hospital discharge, and follow-up	No
Secondary	Exacerbation of Chronic Pulmonary Disease Tool (EXACT) score		Days 5, 10 and 28	No
Secondary	Time to discharge	Number of days from hospital admission to hospital discharge	Hospital discharge	No
Secondary	Recurrent exacerbation, readmission, and death rate	Rates of recurrent exacerbation (defined as treatment with antibiotics and/or systemic corticosteroids for breathlessness, cough or wheeze), readmission to hospital, or death	3 months	No
Secondary	Insulin requirement during hospitalisation period	Mean daily insulin use during hospitalisation period following study entry	During hospitalisation period following study entry	No
Secondary	Haemoglobin A1c	Mean haemoglobin A1c concentration	Follow-up (one month post study entry)	No
Secondary	C-reactive protein concentration	Mean concentration of C-reactive protein in the blood	Days 7 and follow-up (one month)	No
Secondary	Body mass index		Follow-up (one month)	No
Secondary	Waist circumference		Follow-up (one month)	No
Secondary	Forced expiratory volume in 1 second	Mean forced expiratory volume in 1 second (FEV1) expressed as a percentage of predicted value	At hospital discharge and follow-up (one month)	No
Secondary	Fructosamine	Mean serum fructosamine concentration	At hospital discharge and follow-up (one month)	No
Secondary	Interleukin 6	Serum concentration of IL-6 (absolute value and change from baseline)	At hospital discharge and follow-up (one month)	No
Secondary	Interleukin 8	Serum concentration of IL-8 (absolute value and change from baseline)	At hospital discharge and follow-up (one month)	No
Secondary	Tumor necrosis factor alpha	Serum concentration of TNF-alpha (absolute value and change from baseline)	At hospital discharge and follow-up (one month)	No
Secondary	Interferon gamma	Serum concentration of IFN-gamma (absolute value and change from baseline)	At hospital discharge and follow-up (one month)	No
Secondary	8-isoprostane	Serum concentration of 8-isoprostane (absolute value and change from baseline)	At hospital discharge and follow-up (one month)	No
Secondary	Total carbonyl stress	Total carbonyl stress, measured in serum (absolute value and change from baseline)	At hospital discharge and follow-up (one month)	No
Secondary	Glutathione reduced vs oxidised	Glutathione reduced vs oxidised, measured in serum (absolute value and change from baseline)	At hospital discharge and follow-up (one month)	No