Chronic Obstructive Pulmonary DiseasePhase 2NCT03651895
Metformin to Reduce Airway Glucose in COPD Patients
A Phase 2 study testing Metformin in people with Chronic Obstructive Pulmonary Disease, run by Imperial College London at 1 site in United Kingdom.
Trial summary
Chronic obstructive pulmonary disease (COPD) is the 4th leading cause of death worldwide and affects 1.2 million people in the UK, costing the NHS >£800 million annually. COPD patients are more susceptible to bacterial infections and both chronic and acute infections are common. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Metformin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 17 May 2022to 1 Jun 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 40 and 75 years
- Clinical diagnosis of COPD confirmed with spirometry (Post-bronchodilator FEV1/FVC <70%).
- Smoking history >15 pack years
- Absence of infection >8 weeks prior to study entry
- No use of antibiotics and/or oral corticosteroids >8 weeks prior to study entry
- Able to understand and consent to the study procedures
Who cannot join
- Diabetes including diabetes diagnosed at screening
- History of hepatic or renal impairment or diagnosed on screening bloods
- Patients already taking metformin irrespective of indication
- Known allergy or hypersensitivity to metformin
- Pregnancy or breastfeeding
- Any other significant medical condition likely to interfere with the study
Show all 9Show fewer
- Unable to provide informed consent
- Excessive alcohol intake (>21 units/week)
- BMI < 18.5kg/m2
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial College Respiratory Research Unit, St Mary's Hospital
London, Greater London, W2 1NY
About this study
Chronic obstructive pulmonary disease (COPD) is the 4th leading cause of death worldwide and affects 1.2 million people in the UK, costing the NHS >£800 million annually. COPD patients are more susceptible to bacterial infections and both chronic and acute infections are common. COPD patients with chronic lung bacterial infection have worse quality of life, faster disease progression, more symptoms and frequent exacerbations. Acute infections are the main cause of COPD exacerbations which cause COPD patients to become acutely unwell and often result in hospitalisation especially in the winter. Antibiotics are frequently used to treat COPD exacerbations and this contributes to the development of antibiotic resistance. Therefore there is a need to develop antibiotic-independent approaches to reducing or preventing bacterial infection in COPD.
The investigators have carried out work in in animal studies and in humans showing that there is a link between high levels of glucose in the lung and bacterial lung infection. Levels of glucose in the lung are higher in COPD patients compared with people without COPD. These higher glucose levels support greater bacterial growth probably because glucose is a nutrient for bacteria. Therefore reducing airway glucose has the potential to inhibit bacterial growth in COPD patients.
In animal studies the investigators have demonstrated that the diabetic drug metformin decreases airway glucose and bacterial growth. The investigators wish to determine if metformin can achieve the same effects in COPD patients. Metformin is safe and cheap, and has been extensively used in COPD patients with diabetes with an excellent safety record. The primary aim of this study will be to determine whether metformin reduces lung glucose in a small group of non-diabetic COPD patients. If it demonstrates that metformin reduces lung glucose concentrations it will justify a larger clinical trial of metformin as a treatment for COPD.
Read the detailed description
Chronic obstructive pulmonary disease (COPD) is the 4th leading cause of death worldwide and affects 1.2 million people in the UK, costing the NHS >£800 million annually. COPD patients are more susceptible to both chronic and acute bacterial infections. Patients with chronic lung bacterial infection have worse quality of life, faster disease progression, more symptoms and frequent exacerbations. Acute infections are the main cause of acute COPD exacerbations which cause COPD patients to become acutely unwell and often result in hospitalisation especially in the winter. Bacteria are detected in 50-60% of COPD exacerbations. Antibiotics are frequently used to treat COPD exacerbations and this contributes to the development of antibiotic resistance. Therefore any intervention that prevents or reduces bacterial infection in COPD, especially if it is not an antibiotic, will have major benefits for COPD patients, the NHS and for society as a whole.
It is likely that there are many reasons why COPD patients are more susceptible to bacterial infections. From experimental work the investigators have carried out one of the reasons may be high glucose concentrations in the lung.
In healthy lungs glucose levels are kept low and this may be a mechanism that inhibits bacterial growth by depriving them of an essential nutrient. In animal studies the investigators have demonstrated that when levels of glucose in the lung are high, bacterial lung infection is more common. The investigators measured lung glucose concentrations in COPD patients and found that they are higher compared with people without COPD. COPD patients with higher levels of glucose also had more bacteria in their lungs and sputum samples from COPD patients with higher glucose concentrations supported greater bacterial growth in the laboratory.
Therefore this study was the first to link elevated glucose in the lung to bacterial infection in COPD. Therefore reducing airway glucose has the potential to inhibit bacterial growth in COPD patients.
Study Design The proposed study will be a randomised, double-blinded, placebo-controlled, cross-over study of metformin in COPD patients. The primary outcome will be sputum glucose after 3 months' treatment with metformin compared with sputum glucose in those taking placebo. In order to account for potential withdrawals 40 subjects will be recruited.
Study Procedures Potential participants will attend for a screening visit where they will have a full medical history, a physical examination and spirometry carried out to confirm the diagnosis of COPD. A blood test will also be done to measure kidney and liver function and blood glucose to exclude undiagnosed diabetes, kidney disease or liver disease.
If they fulfil the entry criteria and consent to taking part in the study they will have a baseline visit prior to being randomised.
The baseline visit will include:
- Physical examination and measurement of vital signs
- Completion of quality of life (St George's Respiratory Questionnaire (SGRQ)) and symptom questionnaires (COPD Assessment Test (CAT))
- Collection of samples. The samples collected will include blood samples, nose samples collected using nasal synthetic absorption matrix (SAM) strips and induced sputum.
After baseline assessment, subjects will either be commenced on metformin (500mg twice a day after meals) or placebo for 3 months during which time the participants will have monthly visits. At these visits the same assessments and sampling as the baseline will be carried out, together with collection of data regarding exacerbations and adverse events. Following a 2 week washout period the subjects will crossover to the other study arm for another 3 months and follow the same study protocol.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Metformin, Placebo
- Keywords
- Chronic Obstructive Pulmonary Disease
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
The Drug was administered 500 mg twice daily for one week and increased to 1g twice daily for the reminder of the 3 months.
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group | Active comparator | Metformin 500mg/1g bd Receives: Drug: Metformin |
| Placebo Group | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sputum Glucose Concentration
The median concentration of glucose in sputum following 3 months treatment with metformin or placebo.
Measured: 3 months
Secondary outcomes (6)
Nasal Glucose Concentrations
The median concentration of glucose in nasal samples following 3 months treatment with metformin or placebo.
Measured: 3 months
Sputum Bacterial Load
The bacterial load in sputum using qPCR was not measured. Therefore, data were not collected
Measured: 3 months
Sputum Inflammatory Markers
The median concentration of inflammatory cells and cytokines in sputum was not measured. Therefore, data were not collected.
Measured: 3 months
Quality of Life Score (COPD Assessment Test)
The COPD Assessment Test (CAT): the CAT features 8 questions ranked from 0-5 with a minimum score of 0 and maximum possible score of 40. Higher scores indicate a greater impact on patient health due to their COPD, a difference of ≥2 is considered meaningful.
The questionnaire's were completed by every participant at every visit up to 8 times: V1 is at the baseline, then V2-4 are at monthly intervals. V5 is at the baseline after crossing arms -1 month washout, V6-8 are monthly after that.
Measured: 1 month
Quality of Life Score (St George's Respiratory Questionnaire)
St George's Respiratory Questionnaire (SGRQ): the SGRQ contains 50 items with a minimum score of 0 and a maximum score of 100. Higher scores indicate a greater impact on quality of life due to COPD and a difference of ≥4 is meaningful
The questionnaire's were completed by every participant at every visit up to 8 times: V1 is at the baseline, then V2-4 are at monthly intervals. V5 is at the baseline after crossing arms -1 month washout, V6-8 are monthly after that.
Measured: 1 month
Lung Function
FEV1(Forced Expiratory Volume Test) was performed up to 8 times: V1 is at the baseline, then V2-4 are at monthly intervals. V5 is at the baseline after crossing arms -1 month washout, V6-8 are monthly after that.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2018
- Study start17 May 2022
- Primary completion31 May 2023
- Study completion1 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sebastian Johnston, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03651895
- Sponsor's protocol ID
- 18SM4819
- Other IDs
- 2018-001755-12, 2018
- Status last verified
- Feb 2025
- First submitted
- 2 Aug 2018
- Last updated
- 18 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin to Reduce Airway Glucose in COPD Patients
- ClinicalTrials.gov ID
- NCT03651895
- Acronym / sponsor ID
- 18SM4819
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- Chronic Obstructive Pulmonary Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 17 May 2022 (actual)
- Primary completion
- 31 May 2023 (actual)
- Study completion
- 1 Jun 2023 (actual)
- First posted
- 29 Aug 2018 (actual)
- Results
- Posted 18 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic obstructive pulmonary disease (COPD) is the 4th leading cause of death worldwide and affects 1.2 million people in the UK, costing the NHS >£800 million annually. COPD patients are more susceptible to bacterial infections and both chronic and acute infections are common. COPD patients with chronic lung bacterial infection have worse quality of life, faster disease progression, more symptoms and frequent exacerbations. Acute infections are the main cause of COPD exacerbations which cause COPD patients to become acutely unwell and often result in hospitalisation especially in the winter. Antibiotics are frequently used to treat COPD exacerbations and this contributes to the development of antibiotic resistance. Therefore there is a need to develop antibiotic-independent approaches to reducing or preventing bacterial infection in COPD.
The investigators have carried out work in in animal studies and in humans showing that there is a link between high levels of glucose in the lung and bacterial lung infection. Levels of glucose in the lung are higher in COPD patients compared with people without COPD. These higher glucose levels support greater bacterial growth probably because glucose is a nutrient for bacteria. Therefore reducing airway glucose has the potential to inhibit bacterial growth in COPD patients.
In animal studies the investigators have demonstrated that the diabetic drug metformin decreases airway glucose and bacterial growth. The investigators wish to determine if metformin can achieve the same effects in COPD patients. Metformin is safe and cheap, and has been extensively used in COPD patients with diabetes with an excellent safety record. The primary aim of this study will be to determine whether metformin reduces lung glucose in a small group of non-diabetic COPD patients. If it demonstrates that metformin reduces lung glucose concentrations it will justify a larger clinical trial of metformin as a treatment for COPD.
Detailed description
Chronic obstructive pulmonary disease (COPD) is the 4th leading cause of death worldwide and affects 1.2 million people in the UK, costing the NHS >£800 million annually. COPD patients are more susceptible to both chronic and acute bacterial infections. Patients with chronic lung bacterial infection have worse quality of life, faster disease progression, more symptoms and frequent exacerbations. Acute infections are the main cause of acute COPD exacerbations which cause COPD patients to become acutely unwell and often result in hospitalisation especially in the winter. Bacteria are detected in 50-60% of COPD exacerbations. Antibiotics are frequently used to treat COPD exacerbations and this contributes to the development of antibiotic resistance. Therefore any intervention that prevents or reduces bacterial infection in COPD, especially if it is not an antibiotic, will have major benefits for COPD patients, the NHS and for society as a whole.
It is likely that there are many reasons why COPD patients are more susceptible to bacterial infections. From experimental work the investigators have carried out one of the reasons may be high glucose concentrations in the lung.
In healthy lungs glucose levels are kept low and this may be a mechanism that inhibits bacterial growth by depriving them of an essential nutrient. In animal studies the investigators have demonstrated that when levels of glucose in the lung are high, bacterial lung infection is more common. The investigators measured lung glucose concentrations in COPD patients and found that they are higher compared with people without COPD. COPD patients with higher levels of glucose also had more bacteria in their lungs and sputum samples from COPD patients with higher glucose concentrations supported greater bacterial growth in the laboratory.
Therefore this study was the first to link elevated glucose in the lung to bacterial infection in COPD. Therefore reducing airway glucose has the potential to inhibit bacterial growth in COPD patients.
Study Design The proposed study will be a randomised, double-blinded, placebo-controlled, cross-over study of metformin in COPD patients. The primary outcome will be sputum glucose after 3 months' treatment with metformin compared with sputum glucose in those taking placebo. In order to account for potential withdrawals 40 subjects will be recruited.
Study Procedures Potential participants will attend for a screening visit where they will have a full medical history, a physical examination and spirometry carried out to confirm the diagnosis of COPD. A blood test will also be done to measure kidney and liver function and blood glucose to exclude undiagnosed diabetes, kidney disease or liver disease.
If they fulfil the entry criteria and consent to taking part in the study they will have a baseline visit prior to being randomised.
The baseline visit will include:
- Physical examination and measurement of vital signs
- Completion of quality of life (St George's Respiratory Questionnaire (SGRQ)) and symptom questionnaires (COPD Assessment Test (CAT))
- Collection of samples. The samples collected will include blood samples, nose samples collected using nasal synthetic absorption matrix (SAM) strips and induced sputum.
After baseline assessment, subjects will either be commenced on metformin (500mg twice a day after meals) or placebo for 3 months during which time the participants will have monthly visits. At these visits the same assessments and sampling as the baseline will be carried out, together with collection of data regarding exacerbations and adverse events. Following a 2 week washout period the subjects will crossover to the other study arm for another 3 months and follow the same study protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Group | Active comparator | Drug: MetforminMetformin 500mg/1g bd |
| Placebo Group | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age between 40 and 75 years
- Clinical diagnosis of COPD confirmed with spirometry (Post-bronchodilator FEV1/FVC <70%).
- Smoking history >15 pack years
- Absence of infection >8 weeks prior to study entry
- No use of antibiotics and/or oral corticosteroids >8 weeks prior to study entry
Key exclusion criteria (9 listed)
- Diabetes including diabetes diagnosed at screening
- History of hepatic or renal impairment or diagnosed on screening bloods
- Patients already taking metformin irrespective of indication
- Known allergy or hypersensitivity to metformin
- Pregnancy or breastfeeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminThe Drug was administered 500 mg twice daily for one week and increased to 1g twice daily for the reminder of the 3 months. | Drug | Treatment Group |
| PlaceboPlacebo | Drug | Placebo Group |
Primary outcome
Sputum Glucose Concentration
Time frame: 3 months
The median concentration of glucose in sputum following 3 months treatment with metformin or placebo.
6 secondary outcomes
Nasal Glucose Concentrations
Time frame: 3 months
Sputum Bacterial Load
Time frame: 3 months
Sputum Inflammatory Markers
Time frame: 3 months
Quality of Life Score (COPD Assessment Test)
Time frame: 1 month
Quality of Life Score (St George's Respiratory Questionnaire)
Time frame: 1 month
Lung Function
Time frame: 1 month
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sebastian Johnston principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin in people with Chronic Obstructive Pulmonary Disease, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sputum Glucose Concentration (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2025.