Effect of statins on functional regulation of endothelial nitric oxide synthase (eNOS) in heart failure

ISRCTN	ISRCTN41260134
DOI	https://doi.org/10.1186/ISRCTN41260134
Secondary identifying numbers	Sponsors ref: 07009GM-A

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

Not provided at time of registration

Contact information

Dr Mark Harbinson
Scientific

Department of Therapeutics and Pharmacology
Whitla Medical Building
Lisburn Road
Belfast
BT9 7BL
United Kingdom

Study information

Study design	Parallel group double-blind randomised placebo-controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient 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 hypothesis	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
Condition	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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Simvastatin
Primary outcome measure	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.
Secondary outcome measures	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.
Overall study start date	01/11/2008
Overall study end date	30/11/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	60
Participant 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
Participant 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
Recruitment start date	01/11/2008
Recruitment end date	30/11/2011

Locations

Countries of recruitment

Northern Ireland
United Kingdom

Study participating centre

Department of Therapeutics and Pharmacology

Belfast
BT9 7BL
United Kingdom

Sponsor information

Belfast Health and Social Care Trust (UK)
Hospital/treatment centre

Postgraduate Office
Belfast City Hosptial
Lisburn Road
Belfast
BT7 9AB
Northern Ireland
United Kingdom

Website	http://www.belfasttrust.hscni.net
"ROR"	https://ror.org/02tdmfk69

Funders

Funder type

Government

Research and Development Office of the Central Services Agency, Northern Ireland (UK) (ref: EAT/3719/07)

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?
HRA research summary			28/06/2023	No	No

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.