We are investigating the effects of Simvastatin 80mg on neutrophil function (using in vitro studies of neutrophil function), in healthy elderly subjects as there is evidence to suggest that Simvastatin may improve neutrophil responses to inflammation in this population. Clinical and experimental data have suggested that response to infection is improved in patients receiving statins. Our own preliminary in vitro data suggest that this may be due to enhance neutrophil migration.
Conditions
Interventions
Trade Name: Simastatin 80mg once daily
Product Name: Simvastatin
Product Code: PL0025/0366
Pharmaceutical Form: Tablet
INN or Proposed INN: Simvastatin
CAS Number: 79902-63
Other descriptive name: Sim
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria 1. Age > 60 years 2. Competent to provide informed consent and participate 3. MRC Dyspnoea scale 80% predicted, FVC > 80% predicted) 5. Normal peripheral oxygenation (as assessed by pulse oximetry, with oxygen saturations above 92%) 6. Free from medications known to alter immune cell function (as outlined in protocol) 7. No clinical evidence of acute infection or chronic illness. 8. Normal liver and kidney function as assessed by peripheral blood liver function tests, urea and creatinine and urinary dipstick. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 33
Exclusion criteria
Exclusion criteria: Exclusion criteria 1. Unable to provide informed written consent 2. History of significant chronic illness including Diabetes, COPD, Asthma, TB, Bronchiectasis, Malignancy, Auto immune disease, Cardiovascular disease. 3. Clinical evidence of acute viral or bacterial infection 4. Any regular medical therapies that may alter immune function 5. Declines to provide permission for GP to be informed 6. Any contraindications for statin therapy (hypersensitivity or abnormal renal or liver function tests)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Hypothesis. The age-related loss of neutrophil function contributes to delayed resolution of infection and inflammation. These changes in neutrophil function with advanced age are a result of alterations in signal transduction pathways due to altered membrane cholesterol levels and can be corrected using simvastatin. In vitro studies have confirmed that neutrophils isolated from elderly subjects respond differently to those from young donors in terms of migration, phagocytosis and superoxide production when pre-treated with physiological concentrations of Simvastatin. Question: Is this clinically relevant in vivo? Does a course of treatment with simvastatin improve migratory dynamics, phagocytosis and superoxide generation of neutrophils isolated from the peripheral blood of older subjects and is this associated with altered membrane cholesterol levels?;Secondary Objective: There are no secondary questions.;Primary end point(s): 1. Assessment of adhesion, chemokinesis and chemotaxis by neutrophils Neutrophil adhesion and migration will be assessed in a microscopy slide based system using established methodology (35). Chemoattractants used will be those that act via CXC receptors (CXCL8 and GROa), those that act through other receptors (e.g., fMLP). 2. Cell surface receptors. Isolated neutrophils from both media will also be used to measure surface expression of receptors known to be important in chemotaxis, including CXCR1, CXCR2, CD11, CD18, CD44, CD47 and CD55, using FACS analysis, to assess differences in migratory receptor and opsonisation receptor expression. 3. Assessment of bacterial killing The phagocytic function and superoxide production of neutrophils will be examined using standard assays. Respiratory burst in response to fMLP will be determined in isolated neutrophils by measuring the generation of superoxide in a lucigenin-based assay. Phagocytosis of E Coli by neutrophils will be measured using a commercially available kit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Nil;Timepoint(s) of evaluation of this end point: N/A | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trials Coordinator
Queen Elizabeth Hospital Birmingham NHS Trust
Outcome results
None listed