Trial Outcomes & Findings for Metformin to Reduce Airway Glucose in COPD Patients (NCT NCT03651895)

NCT ID: NCT03651895

Last Updated: 2025-02-18

Results Overview

The median concentration of glucose in sputum following 3 months treatment with metformin or placebo.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 14 participants
• Primary outcome timeframe: 3 months
• Results posted on: 2025-02-18

Participant Flow

Overall treatment time 6 months (2 milestones at 1 and 3 months)

14 participants were enrolled but 11 withdrew for lower/upper respiratory tract infections (LRTI/URTI) Cough and Vomiting. At 3 months there was a washout and a crossover thereafter.

Participant milestones

Measure	Metformin First (Before Crossover), Placebo Second (After Crossover) Metformin 500 milligrams (mg)/1 gram (g) twice daily. Metformin: 500mg twice daily was administered for one week and increased to 1g twice daily for the reminder of the 3 months. Placebo Placebo: The drug was administered with the same regime as the metformin.	Placebo First (Before Crossover), Metformin Second (After Crossover) Metformin 500 milligrams (mg)/1 gram (g) twice daily. Metformin: 500mg twice daily was administered for one week and increased to 1g twice daily for the reminder of the 3 months. Placebo Placebo: The drug was administered with the same regime as the metformin.
First Drug Assignment STARTED	7	7
First Drug Assignment 1 Month	6	6
First Drug Assignment 3 Months	3	2
First Drug Assignment COMPLETED	3	2
First Drug Assignment NOT COMPLETED	4	5
Second Drug Assignment - Crossover STARTED	2	3
Second Drug Assignment - Crossover 1 Month	2	2
Second Drug Assignment - Crossover COMPLETED	1	2
Second Drug Assignment - Crossover NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Metformin First (Before Crossover), Placebo Second (After Crossover) Metformin 500 milligrams (mg)/1 gram (g) twice daily. Metformin: 500mg twice daily was administered for one week and increased to 1g twice daily for the reminder of the 3 months. Placebo Placebo: The drug was administered with the same regime as the metformin.	Placebo First (Before Crossover), Metformin Second (After Crossover) Metformin 500 milligrams (mg)/1 gram (g) twice daily. Metformin: 500mg twice daily was administered for one week and increased to 1g twice daily for the reminder of the 3 months. Placebo Placebo: The drug was administered with the same regime as the metformin.
First Drug Assignment Adverse Event	4	5
Second Drug Assignment - Crossover Adverse Event	1	1

Baseline Characteristics

Metformin to Reduce Airway Glucose in COPD Patients

Baseline characteristics by cohort

Measure	Treatment Group & Placebo Group n=14 Participants Placebo Or Metformin 500mg/1g bd Metformin: The Drug was administered 500 mg twice daily for one week and increased to 1g twice daily for the reminder of the 3 months.
Age, Customized Age	67.9 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Race/Ethnicity, Customized White	12 Participants n=5 Participants
Race/Ethnicity, Customized Others	2 Participants n=5 Participants
Region of Enrollment United Kingdom	14 participants n=5 Participants
Forced Expiratory Volume in One Second (FEV1) Percentage (%) Predicted	68.2 Percentage(%) predicted STANDARD_DEVIATION 17.8 • n=5 Participants
Forced Vital Capacity (FVC) Percentage (%) Predicted	100.3 Percentage (%) predicted STANDARD_DEVIATION 15.1 • n=5 Participants
Peak Expiratory Flow (PEF) Percentage (%) Predicted	65.4 Percentage (%) predicted STANDARD_DEVIATION 22.8 • n=5 Participants
COPD Assessment Test (CAT)	15.4 Score on a scale STANDARD_DEVIATION 9.3 • n=5 Participants
St George's Respiratory Questionnaire (SGRQ)	41.8 Score on a scale STANDARD_DEVIATION 16.2 • n=5 Participants
Sputum Glucose Concentration	5.3 µmol n=5 Participants

PRIMARY outcome

Timeframe: 3 months

The median concentration of glucose in sputum following 3 months treatment with metformin or placebo.

Outcome measures

Measure	Treatment Group n=4 Participants Metformin 500mg/1g bd Metformin: The Drug was administered 500 mg twice daily for one week and increased to 1g twice daily for the reminder of the 3 months.	Placebo Group n=4 Participants Placebo Placebo: Placebo
Sputum Glucose Concentration	68.92 µM Interval 16.3 to 131.1	12.2 µM Interval 10.0 to 13.0

SECONDARY outcome

Timeframe: 3 months

The median concentration of glucose in nasal samples following 3 months treatment with metformin or placebo.

Outcome measures

Measure	Treatment Group n=4 Participants Metformin 500mg/1g bd Metformin: The Drug was administered 500 mg twice daily for one week and increased to 1g twice daily for the reminder of the 3 months.	Placebo Group n=4 Participants Placebo Placebo: Placebo
Nasal Glucose Concentrations	12.56 µM Interval 5.92 to 28.28	13.5 µM Interval 6.19 to 27.83

SECONDARY outcome

Timeframe: 3 months

Population: Data were not collected. Participants with infection were excluded from the study.

The bacterial load in sputum using qPCR was not measured. Therefore, data were not collected

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3 months

Population: Data were not collected. Participants with infection were excluded from the study.

The median concentration of inflammatory cells and cytokines in sputum was not measured. Therefore, data were not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 month

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.

Outcome measures

Measure	Treatment Group n=8 Participants Metformin 500mg/1g bd Metformin: The Drug was administered 500 mg twice daily for one week and increased to 1g twice daily for the reminder of the 3 months.	Placebo Group n=8 Participants Placebo Placebo: Placebo
Quality of Life Score (COPD Assessment Test)	16.6 Score on a scale Interval 6.4 to 26.8	13.2 Score on a scale Interval 3.3 to 23.1

SECONDARY outcome

Timeframe: 1 month

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.

Outcome measures

Measure	Treatment Group n=8 Participants Metformin 500mg/1g bd Metformin: The Drug was administered 500 mg twice daily for one week and increased to 1g twice daily for the reminder of the 3 months.	Placebo Group n=8 Participants Placebo Placebo: Placebo
Quality of Life Score (St George's Respiratory Questionnaire)	42.7 Score on a scale Interval 24.4 to 61.0	36.4 Score on a scale Interval 18.6 to 54.2

SECONDARY outcome

Timeframe: 1 month

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.

Outcome measures

Measure	Treatment Group n=8 Participants Metformin 500mg/1g bd Metformin: The Drug was administered 500 mg twice daily for one week and increased to 1g twice daily for the reminder of the 3 months.	Placebo Group n=8 Participants Placebo Placebo: Placebo
Lung Function	69.2 Litres (L) Interval 51.0 to 87.4	66.1 Litres (L) Interval 46.7 to 85.5

Adverse Events

Treatment Group

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo Group

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment Group n=14 participants at risk Metformin 500mg/1g bd Metformin: The Drug was administered 500 mg twice daily for one week and increased to 1g twice daily for the reminder of the 3 months.	Placebo Group n=14 participants at risk Placebo Placebo: The Drug was administered 500 mg twice daily for one week and increased to 1g twice daily for the reminder of the 3 months.
Respiratory, thoracic and mediastinal disorders Exacerbation of COPD with hospitalisation	0.00% 0/14 • 1 year Adverse events were reviewed at every study visit.	7.1% 1/14 • 1 year Adverse events were reviewed at every study visit.

Other adverse events

Measure	Treatment Group n=14 participants at risk Metformin 500mg/1g bd Metformin: The Drug was administered 500 mg twice daily for one week and increased to 1g twice daily for the reminder of the 3 months.	Placebo Group n=14 participants at risk Placebo Placebo: The Drug was administered 500 mg twice daily for one week and increased to 1g twice daily for the reminder of the 3 months.
Gastrointestinal disorders Nausea	14.3% 2/14 • 1 year Adverse events were reviewed at every study visit.	0.00% 0/14 • 1 year Adverse events were reviewed at every study visit.
Gastrointestinal disorders Vomiting	7.1% 1/14 • 1 year Adverse events were reviewed at every study visit.	7.1% 1/14 • 1 year Adverse events were reviewed at every study visit.
Gastrointestinal disorders Diarrhoea	14.3% 2/14 • 1 year Adverse events were reviewed at every study visit.	7.1% 1/14 • 1 year Adverse events were reviewed at every study visit.
Gastrointestinal disorders Abdominal cramps	7.1% 1/14 • 1 year Adverse events were reviewed at every study visit.	0.00% 0/14 • 1 year Adverse events were reviewed at every study visit.
Respiratory, thoracic and mediastinal disorders Lower respiratory tract infection	21.4% 3/14 • 1 year Adverse events were reviewed at every study visit.	21.4% 3/14 • 1 year Adverse events were reviewed at every study visit.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	0.00% 0/14 • 1 year Adverse events were reviewed at every study visit.	7.1% 1/14 • 1 year Adverse events were reviewed at every study visit.
Respiratory, thoracic and mediastinal disorders Procedural related adverse event	7.1% 1/14 • 1 year Adverse events were reviewed at every study visit.	21.4% 3/14 • 1 year Adverse events were reviewed at every study visit.

Additional Information

Farne Hugo

Imperial College

Phone: +44 (0)20 7589 5111

Email: h.farne@imperial.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place