Metformin to Reduce Airway Glucose in COPD Patients

NCT03651895 | Completed Phase 2 Results

• 2 other identifiers: 18SM48192018-001755-12
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• Sputum Glucose Concentration

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

  3 months

Secondary Outcomes (6)

• Nasal Glucose Concentrations

  3 months

• Sputum Bacterial Load

  3 months

• Sputum Inflammatory Markers

  3 months

• Quality of Life Score (COPD Assessment Test)

  1 month

• Quality of Life Score (St George's Respiratory Questionnaire)

  1 month

Study Arms (2)

Treatment Group

ACTIVE COMPARATOR

Metformin 500mg/1g bd

Drug: Metformin

Placebo Group

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Metformin DRUG

The Drug was administered 500 mg twice daily for one week and increased to 1g twice daily for the reminder of the 3 months.

Treatment Group

Placebo DRUG

Placebo

Placebo Group

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Unable to provide informed consent
• Excessive alcohol intake (\>21 units/week)
• BMI \< 18.5kg/m2

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Imperial College Respiratory Research Unit, St Mary's Hospital

London, Greater London, W2 1NY, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Metformin

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Farne Hugo
• Organization: Imperial College

h.farne@imperial.ac.uk

+44 (0)20 7589 5111

Study Officials

• Sebastian Johnston

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2018
• First Posted: August 29, 2018
• Study Start: May 17, 2022
• Primary Completion: May 31, 2023
• Study Completion: June 1, 2023
• Last Updated: February 18, 2025
• Results First Posted: February 18, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)