Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
060778SE-A
Study information
Scientific title
Acronym
Study hypothesis
Treatment with a clinically relevant dose of simvastatin will reduce pulmonary inflammation induced by lipopolysaccharide (LPS) inhalation in humans.
Ethics approval
Office for Research Ethics Committees Northern Ireland (ORECNI). Date of approval: 25/10/2006 (ref: 06/NIR02/91)
Study design
Prospective, randomised, double-blind, placebo-controlled trial.
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Acute lung injury (ALI)
Intervention
Subjects will be randomised to the following three arms:
Arm 1: Simvastatin 40 mg enterally for 4 days prior to inhalation of LPS
Arm 2: Simvastatin 80 mg enterally for 4 days prior to inhalation of LPS
Arm 3: Placebo enterally for 4 days prior to inhalation of LPS
Intervention type
Drug
Phase
Not Specified
Drug names
simvastatin
Primary outcome measure
Reduction in broncho alveolar lavage (BAL) Interleukin-8 (IL8) concentration at 6 hours
Secondary outcome measures
1. To investigate whether treatment with simvastatin will modulate the following:
1.1. Alveolar inflammatory response at 6 hours
1.2 Plasma inflammatory response at 24 hours
1.3. Alveolar matrix metalloproteinase activity at 6 hours
1.4. Intracellular signalling in the alveolar space at 6 hours
1.5. Indices of alveolar epithelial and endothelial function and injury at 6 hours
2. To determine the potential mechanisms by which simvastatin may be beneficial in ALI
Overall trial start date
02/08/2006
Overall trial end date
05/11/2009
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Healthy subjects, both males and females
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
30
Participant exclusion criteria
1. Age <18 years
2. Creatinine kinase (CK) >5 times upper limit of normal
3. Known active liver disease
4. Alcohol abuse or abnormal liver function tests: transaminases > 3 times upper limit of normal
5. Renal impairment (calculated creatinine clearance less than 60 mL/minute)
6. History of asthma, known lactose intolerance
7. Participation in other trials within the past 30 days
8. Pregnancy, breast-feeding or women of childbearing potential not using adequate contraception;
9. Current treatment with statins
10. Known hypersensitivity to the study medication
11. Previous adverse reaction to statins
12. Concomitant use of fibrates or other lipid-lowering therapy
13. Concomitant use of itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, grapefruit juice, cyclosporine, danazol, amiodarone, verapamil or diltiazem
14. Consent declined
Recruitment start date
02/08/2006
Recruitment end date
05/11/2009
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Intensive Care Unit
Belfast
BT12 6BA
United Kingdom
Sponsor information
Organisation
Belfast Health and Social Care Trust (UK)
Sponsor details
51 Lisburn Road
Belfast
BT9 7AB
United Kingdom
+44 (0)28 90 329241
rosemary.mcveigh@belfasttrust.hscni.net
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Intensive Care Society, Young Investigator's Award (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
REVIVE (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Northern Ireland Health and Social Services Central Services Agency (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
1. 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19324974
Publication citations
-
Results
Shyamsundar M, McKeown ST, O'Kane CM, Craig TR, Brown V, Thickett DR, Matthay MA, Taggart CC, Backman JT, Elborn JS, McAuley DF, Simvastatin decreases lipopolysaccharide-induced pulmonary inflammation in healthy volunteers., Am. J. Respir. Crit. Care Med., 2009, 179, 12, 1107-1114, doi: 10.1164/rccm.200810-1584OC.