Effect of statins on functional regulation of endothelial nitric oxide synthase (eNOS) in heart failure
| ISRCTN | ISRCTN41260134 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN41260134 |
| Protocol serial number | Sponsors ref: 07009GM-A |
| Sponsor | Belfast Health and Social Care Trust (UK) |
| Funder | Research and Development Office of the Central Services Agency, Northern Ireland (UK) (ref: EAT/3719/07) |
- Submission date
- 19/09/2008
- Registration date
- 27/10/2008
- Last edited
- 09/06/2016
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
Not provided at time of registration
Contact information
Scientific
Department of Therapeutics and Pharmacology
Whitla Medical Building
Lisburn Road
Belfast
BT9 7BL
United Kingdom
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Parallel group double-blind randomised placebo-controlled trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibition on endothelial dysfunction, bioavailability of tetrahydrobiopterin (BH4) and functional regulation of endothelial nitric oxide synthase (eNOS) in human heart failure |
| Study objectives | Treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co-A) reductase inhibitors in patients with heart failure will result in reduced uncoupling of endothelial nitric oxide synthase (eNOS), detected biochemically by increased production of nitric oxide and reduced production of free radicals and functionally by improved flow mediated dilatation of the brachial artery and changes in velocity time waveforms; and that these changes can be explained in part by detection of increased levels of tetrahydrobiopterin (BH4). |
| Ethics approval(s) | Health and Social Care Research Ethics Committee 1, 28/10/2008, ref: 08/NIR01/74 |
| Health condition(s) or problem(s) studied | Heart failure with systolic dysfunction |
| Intervention | Simvastatin 40 mg orally (or placebo) once a day (in the evening) will be administered for 6 weeks to each study participant. |
| Intervention type | Drug |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Simvastatin |
| Primary outcome measure(s) |
Changes in levels of superoxide, peroxynitrite, nitric oxide, tetrahydrobiopterin and brachial artery flow mediated dilatation and pulse contour analysis. Each outcome measure will be assessed at an initial visit, and then following randomisation and 6 weeks of treatment. |
| Key secondary outcome measure(s) |
Changes in levels of markers of left ventricular (LV) dysfunction, adrenomedullin, N-terminal prohormone brain natriuretic peptide (NT proBNP) and intermedin. Each outcome measure will be assessed at an initial visit, and then following randomisation and 6 weeks of treatment. |
| Completion date | 30/11/2011 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 60 |
| Key inclusion criteria | 1. Both males and females, over 18 years of age 2. Diagnosis of heart failure with an ejection fraction less than 35% determined by 2D echocardiography. Patients will be typically receiving maximal therapy for treatment of heart failure, including loop diuretics, angiotensin converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers and spironolactone. 3. Patients must also be able to give informed consent, and to attend for follow up appointments |
| Key exclusion criteria | 1. History of diabetes mellitus (fasting glucose greater than 7 mmol/L) or uncontrolled hypertension (blood pressure [BP] greater than 140/90 mmHg) or are receiving the thienopyridine derivative clopidogrel 2. Abnormal liver function (defined as aspartate aminotransferase [AST] or alanine aminotransferase [ALT] greater than three times upper limit of normal) or have had a previous documented adverse reaction to statin therapy or hypersensitivity to simvastatin or any of the excipients 3. Pregnant or lactating 4. Any patient who has an adverse reaction to statin therapy following initiation of treatment 5. Patients taking potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, human immunodeficiency virus [HIV] protease inhibitors, erythromycin, clarithromycin) 6. Patients taking cyclosporin, gemfibrozil or greater than 1 g/day niacin |
| Date of first enrolment | 01/11/2008 |
| Date of final enrolment | 30/11/2011 |
Locations
Countries of recruitment
- United Kingdom
- Northern Ireland
Study participating centre
BT9 7BL
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
09/06/2016: No publications found, verifying study status with principal investigator.
08/05/2013: The anticipated end date for this trial was updated from 03/08/2010 to 30/11/2011
09/02/2009: This record was updated to include an amended anticipated start date. The initial anticipated start date was 06/08/2008.
