THANOS
Research type
Research Study
Full title
Targeting Human AMPK: a New Observational Study
IRAS ID
268260
Contact name
James Chalmers
Contact email
Sponsor organisation
University of Dundee / NHS Tayside
Duration of Study in the UK
0 years, 11 months, 30 days
Research summary
Bronchiectasis is a disease characterised by daily cough, sputum production and frequent chest infections with no medications currently licensed. The vicious cycle of bronchiectasis is dominated by neutrophilic inflammation. Neutrophils are short lived inflammatory cells which migrate to the lungs and are designed to rapidly eliminate bacterial pathogens. In bronchiectasis, however, neutrophilic inflammation persists despite a failure to resolve bacterial infection leading to chronic inflammation and long term infections. The reasons for the failure of neutrophil function are unknown.
Previous studies have given conflicting data on whether neutrophils in bronchiectasis are abnormal in the blood and airways. Few studies have compared function between a patients and a matched cohort of healthy subjects.
Recently the concept of metabolic reprogramming of neutrophils and other inflammatory cells has been suggested as a mechanism of chronic inflammation. It has been suggested that inflammatory cells become dysfunctional in their utilisation of energy leading to poor function and prolonged lifespan. The role of metabolic reprograming in bronchiectasis cells has not been investigated.
In this study we will take approximately 50ml of blood, urine and a sputum sample from up to 40 patients with bronchiectasis and blood, urine and a nasal brushing from up to 40 age and sex matched healthy controls without bronchiectasis or any other respiratory or chronic inflammatory disease. The data generated from the study will be used to test whether patients with bronchiectasis show neutrophil dysfunction in the blood and airways, and secondly whether AMPK activator drugs which are potentially able to reverse metabolic reprogramming, enhancing phagocytosis and bacterial killing, can demonstrate benefits ex-vivo.
REC name
West of Scotland REC 1
REC reference
19/WS/0173
Date of REC Opinion
12 Nov 2019
REC opinion
Further Information Favourable Opinion