Improving neutrophil responses in pneumonia using simvastatin

• Research type

  Research Study

• Full title

  Simvastatin as adjuvant therapy to correct neutrophil dysfunction in older pneumonia patients - a randomised double blind placebo controlled trial

• IRAS ID

  110966

• Contact name

  David Thickett

• Eudract number

  2012-003343-29

• ISRCTN Number

  N/A

• Clinicaltrials.gov Identifier

  N/A

• Research summary

  The efficiency of the immune system declines with age (immunosenescence) with an increased risk of morbidity and mortality from infection in the elderly. The increased incidence of bacterial infections in older adults is particularly suggestive of a sub-optimal neutrophil response, as these leucocytes form the primary cellular response to bacterial infections. Comparison of neutrophils from healthy young and older adults has shown that bactericidal (superoxide generation), phagocytic function and neutrophil migration (movement towards inflammation and infection) are dramatically reduced in neutrophils from older adults, even during health. Pneumonia is the commonest infective cause of death in older adults worldwide, and mortality rates have not improved over the last 10 years. New treatment strategies are required. HMGCoA reductase inhibitors (commonly known as statins) are well-tolerated medications taken by millions of people worldwide to reduced cholesterol levels in the blood. Experimental and clinical research suggests that statins may improve outcomes after severe infections including during pneumonia. Our data suggest a mechanism for this. Statins improve neutrophil functions vital in clearing bacteria (with more accurate migration and increased phagocytosis) but are more effective in older subjects (where neutrophil function is reduced). This is highly important. Improving neutrophil functions could lead to more controlled and effective immune responses during infective episodes in older subjects, potentially improving clinical outcomes. Statins may represent a well-tolerated and safe means to optimise neutrophil functions. We would like to study the effects of taking statins on neutrophil function during pneumonia, in a randomised, double blind placebo controlled trial. Patients admitted with pneumonia would be placed on Simvastatin or placebo, with blood neutrophil function being compared before and after treatment. We will test if neutrophil responses improve on Statin therapy, in terms of migration, and clearance of bacteria (as our preliminary data predicts).

• REC name

  Yorkshire & The Humber - Leeds West Research Ethics Committee

• REC reference

  12/YH/0375

• Date of REC Opinion

  17 Oct 2012

• REC opinion

  Further Information Favourable Opinion