Coronary Artery Disease MedDRA version: 8.1 Level: LLT Classification code 10011078 Term: Coronary artery disease
Conditions
Interventions
Product Name: 6R-BH4
Product Code: T1401
Pharmaceutical Form: Soluble tablet
INN or Proposed INN: sapropterin dihydrochloride
CAS Number: 69056-38-8
Current Sponsor code: T1401
Concentration unit: mg
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Male or Female, aged 18 years or above. -Multivessel coronary artery disease scheduled to undergo coronary bypass surgery. -Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study. -Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study. 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
Exclusion criteria
Exclusion criteria: -Pregnant or breastfeeding at screening or planning to become pregnant (subject of partner) at any time during study. -Prior clinical diagnosis of heart failure requiring diuretic treatment with evidence of severe left ventricular dysfunction. -Acute coronary event (unstable angina requiring hospitalisation, myocardial infarction) within the last 4 weeks. -Emergency CABG. -Newly diagnosed diabetes mellitus (130 kg. -Impaired renal function (plasma creatinine > 180 µmol/l). -Elevated liver function tests (defined as a serum alanine transaminase (ALT) >50µmol/l (or > 2x normal) and/or AST > 2x normal). -Pacemakers, implantable defibrillators or metal implants that are not compatible with MRI scanning. -Subjects receiving experimental medications or participating in another study using an experimental drug or experimental procedure within 30 days of enrollment into this study. -Subject is terminally ill or is inappropriate for placebo medication. -Any other significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or may influence the result of the study, or the subject’s ability to participate in the study. -Requirements for concomitant treatment with any drug known to inhibit folate metabolism (e.g., methotrexate). -Concomitant treatment with levodopa. -Concomitant treatment with any phosphodiesterase (PDE) 5 inhibitors (e.g., Viagra®, Cialis®, Levitra®, or RevatioTM) or any PDE 3 inhibitor (e.g., cilostazol, milrinone, or vesnarinone) -Subjects previously randomised into this study or any other clinical trial involving 6R-BH4 treatment. -Known allergy or hypersensitivity to any excipient of 6R-BH4.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare vascular function in subjects with coronary artery disease before and after treatment with different doses (400mg or 700mg daily) of 6R-BH4 as assessed by non-invasive MRI. The principal markers of vascular function will be aortic distensibility and pressure pulse wave velocity, carotid artery distensibility and brachial artery flow-mediated dilatation. ;Secondary Objective: -To assess the effect of 6R-BH4 treatment on the following markers of vascular function in isolated blood vessels: vascular and myocardial superoxide production, nitric oxide-mediated endothelial function by organ bath isometric tension studies. -To assess the effect of 6R-BH4 treatment on biopterin levels in isolated blood vessels. Tertiary Objectives of the trial: -To assess the effect of 6R-BH4 treatment on insulin resistance (fasting glucose & insulin levels) in type II diabetics. -To assess the effect of 6R-BH4 treatment on systemic blood pressure. -To assess the effect of 6R-BH4 treatment on microalbuminuria. -To assess the effect of 6R-BH4 treatment on urinary isoprostane levels. -To assess the effect of 6R-BH4 treatment on: incidence of post-operative AF, length of ITU stay, length of hospital stay, renal function. -To assess the effect of 6R-BH4 treatment on blood markers of oxidative stress and endothelial function.;Primary end point(s): The primary endpoint will be the effects of 6R-BH4 (400mg or 700mg daily) compared to placebo on the following MRI parameters of vascular function in subjects with CAD: brachial artery reactivity; aortic distensibility; aortic pressure pulse wave velocity; carotid artery distensibility. | — |
Countries
United Kingdom
Outcome results
None listed