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Metformin in Chronic Obstructive Pulmonary Disease

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Medical Research Council
British Lung Foundation
Information provided by (Responsible Party):
St George's, University of London
ClinicalTrials.gov Identifier:
NCT01247870
First received: November 23, 2010
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: Metformin
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Placebo-controlled Trial of Metformin in Chronic Obstructive Pulmonary Disease (COPD) Exacerbations: a Pilot Study

Resource links provided by NLM:


Further study details as provided by St George's, University of London:

Primary Outcome Measures:
  • Capillary glucose concentration [ Time Frame: During hospitalisation period ] [ Designated as safety issue: Yes ]
    The mean capillary glucose concentration during hospitalisation period following study entry, as a measure of both efficacy and safety.


Secondary Outcome Measures:
  • COPD Assessment Test score [ Time Frame: Study entry, hospital discharge, and follow-up ] [ Designated as safety issue: No ]
  • Exacerbation of Chronic Pulmonary Disease Tool (EXACT) score [ Time Frame: Days 5, 10 and 28 ] [ Designated as safety issue: No ]
  • Time to discharge [ Time Frame: Hospital discharge ] [ Designated as safety issue: No ]
    Number of days from hospital admission to hospital discharge

  • Recurrent exacerbation, readmission, and death rate [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Rates of recurrent exacerbation (defined as treatment with antibiotics and/or systemic corticosteroids for breathlessness, cough or wheeze), readmission to hospital, or death

  • Insulin requirement during hospitalisation period [ Time Frame: During hospitalisation period following study entry ] [ Designated as safety issue: No ]
    Mean daily insulin use during hospitalisation period following study entry

  • Haemoglobin A1c [ Time Frame: Follow-up (one month post study entry) ] [ Designated as safety issue: No ]
    Mean haemoglobin A1c concentration

  • C-reactive protein concentration [ Time Frame: Days 7 and follow-up (one month) ] [ Designated as safety issue: No ]
    Mean concentration of C-reactive protein in the blood

  • Body mass index [ Time Frame: Follow-up (one month) ] [ Designated as safety issue: No ]
  • Waist circumference [ Time Frame: Follow-up (one month) ] [ Designated as safety issue: No ]
  • Forced expiratory volume in 1 second [ Time Frame: At hospital discharge and follow-up (one month) ] [ Designated as safety issue: No ]
    Mean forced expiratory volume in 1 second (FEV1) expressed as a percentage of predicted value

  • Fructosamine [ Time Frame: At hospital discharge and follow-up (one month) ] [ Designated as safety issue: No ]
    Mean serum fructosamine concentration

  • Interleukin 6 [ Time Frame: At hospital discharge and follow-up (one month) ] [ Designated as safety issue: No ]
    Serum concentration of IL-6 (absolute value and change from baseline)

  • Interleukin 8 [ Time Frame: At hospital discharge and follow-up (one month) ] [ Designated as safety issue: No ]
    Serum concentration of IL-8 (absolute value and change from baseline)

  • Tumor necrosis factor alpha [ Time Frame: At hospital discharge and follow-up (one month) ] [ Designated as safety issue: No ]
    Serum concentration of TNF-alpha (absolute value and change from baseline)

  • Interferon gamma [ Time Frame: At hospital discharge and follow-up (one month) ] [ Designated as safety issue: No ]
    Serum concentration of IFN-gamma (absolute value and change from baseline)

  • 8-isoprostane [ Time Frame: At hospital discharge and follow-up (one month) ] [ Designated as safety issue: No ]
    Serum concentration of 8-isoprostane (absolute value and change from baseline)

  • Total carbonyl stress [ Time Frame: At hospital discharge and follow-up (one month) ] [ Designated as safety issue: No ]
    Total carbonyl stress, measured in serum (absolute value and change from baseline)

  • Glutathione reduced vs oxidised [ Time Frame: At hospital discharge and follow-up (one month) ] [ Designated as safety issue: No ]
    Glutathione reduced vs oxidised, measured in serum (absolute value and change from baseline)


Estimated Enrollment: 52
Study Start Date: January 2011
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin
Metformin 1 g twice daily for 28-35 days
Drug: Metformin
Metformin 1 g twice daily for 28-35 days
Placebo Comparator: Placebo
Matched placebo capsules
Drug: Placebo
Placebo

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

Ages Eligible for Study:   35 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01247870

Locations
United Kingdom
North Tees and Hartlepool NHS Trust
Hartlepool, Cleveland, United Kingdom, TS24 9AH
University Hospitals of Morecambe Bay NHS Trust
Lancaster, Cumbria, United Kingdom, LA9 7RG
East Sussex Healthcare NHS Trust
Hastings, East Sussex, United Kingdom, TN37 7PT
Blackpool Teaching Hospitals NHS Trust
Blackpool, Lancashire, United Kingdom, FY3 8NR
Lancashire Teaching Hospitals NHS Trust
Preston, Lancashire, United Kingdom, PR2 9HT
Sherwood Forest Hospitals NHS Trust
Sutton-in-Ashfield, Nottinghamshire, United Kingdom, NG17 4JL
Chelsea and Westminster Hospital
London, United Kingdom, SW10 9NH
St George's Hospital
London, United Kingdom, SW17 0QT
Freeman Hospital
Newcastle, United Kingdom, NE7 7DN
Sponsors and Collaborators
St George's, University of London
Medical Research Council
British Lung Foundation
Investigators
Study Chair: Emma H Baker, MBChB PhD St George's, University of London
Principal Investigator: Andrew W Hitchings, BSc MBBS St George's Healthcare NHS Trust
  More Information

No publications provided

Responsible Party: St George's, University of London
ClinicalTrials.gov Identifier: NCT01247870     History of Changes
Other Study ID Numbers: 10.0086, 2010-020818-28
Study First Received: November 23, 2010
Last Updated: March 4, 2014
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by St George's, University of London:
Chronic obstructive pulmonary disease, COPD, metformin

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014