Investigation of the anti-inflammatory effects of simvastatin in a human lipopolysaccharide induced model of acute lung injury
| ISRCTN | ISRCTN21056528 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN21056528 |
| Secondary identifying numbers | 060778SE-A |
- Submission date
- 29/04/2008
- Registration date
- 09/06/2008
- Last edited
- 30/06/2009
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Danny McAuley
Scientific
Scientific
Intensive Care Unit
Royal Victoria Hospital
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
Study information
| Study design | Prospective, randomised, double-blind, placebo-controlled trial. |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | |
| Study objectives | Treatment with a clinically relevant dose of simvastatin will reduce pulmonary inflammation induced by lipopolysaccharide (LPS) inhalation in humans. |
| Ethics approval(s) | Office for Research Ethics Committees Northern Ireland (ORECNI). Date of approval: 25/10/2006 (ref: 06/NIR02/91) |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | 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 study start date | 02/08/2006 |
| Completion date | 05/11/2009 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 30 |
| Key inclusion criteria | Healthy subjects, both males and females |
| Key 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 |
| Date of first enrolment | 02/08/2006 |
| Date of final enrolment | 05/11/2009 |
Locations
Countries of recruitment
- Northern Ireland
- United Kingdom
Study participating centre
Intensive Care Unit
Belfast
BT12 6BA
United Kingdom
BT12 6BA
United Kingdom
Sponsor information
Belfast Health and Social Care Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
51 Lisburn Road
Belfast
BT9 7AB
Northern Ireland
United Kingdom
| Phone | +44 (0)28 90 329241 |
|---|---|
| rosemary.mcveigh@belfasttrust.hscni.net | |
| Website | http://www.belfasttrust.hscni.net |
"ROR" |
https://ror.org/02tdmfk69 |
Funders
Funder type
Government
Intensive Care Society, Young Investigator's Award (UK)
No information available
REVIVE (UK)
No information available
Northern Ireland Health and Social Services Central Services Agency (UK)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 15/06/2009 | Yes | No |
