Effect of HMG-Co A reductase inhibition on endothelial dysfunction, bioavailability of tetrahydrobiopterin (BH4) and functional regulation of endothelial nitric oxide synthase (eNOS) in human heart failure. - Effect of statins on functional regulation of eNOS in heart failure.
- Conditions
- Heart failure
- Registration Number
- EUCTR2008-002287-33-GB
- Lead Sponsor
- Belfast Health and Social Care Trust
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 60
To be eligible for the study, patients must be over 18 years of age and have a diagnosis of heart failure based on transthoracic echocardiogram showing left ventricular ejection fraction less than 35 % with New York Heart Association symptom class II - IV. Patients will typically be receiving maximal medical therapy for heart failure. Patients must also be able to give informed consent and be able to attend the department for investigations.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Patients will be excluded from the study if they have a history of diabetes mellitus (fasting glucose > 7mmol/l), uncontrolled hypertension (BP > 140/90 mmHg) or are receiving the thienopyridine derivative clopidogrel. Patients will also be excluded if they have abnormal liver function (ALT of AST > 3 times upper limit of normal) or have had a previously documented adverse reaction to statin therapy or hypersensitivity to simvastatin or any of the excipients. Females will be excluded if they are pregnant or lactating. Any patient who has an adverse reaction to statin therapy following initiation of treatment, will be excluded from further participation in the study. Patients taking potent CYP3A4 inhibitors (eg. itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin) will be excluded. Patients taking ciclosporin, gemfibrozil, or >1g/day niacin will also be excluded.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Investigate the effect of simvastatin on biochemical and functional measures of endothelial function in patients with heart failure.;Secondary Objective: Measures of surrogate markers of cardiac function including NT pro BNP, intermedin and adrenomedullin (all measured in blood samples);<br> Primary end point(s): The primary endpoints will be difference in biochemical and functional measures of endothelial function between placebo and treatment arms of the study. Biochemical markers compared will be:<br> nitric oxide<br> superoxide<br> peroxynitrite<br> tetrahydrobiopterin<br> NT pro BNP<br> adrenomedullin<br> intermedin<br><br><br> Functional measures will be:<br> fore arm mediated dilatation and<br> pulse contour analysis<br>
- Secondary Outcome Measures
Name Time Method