Effect of 6R-BH4 Treatment in Coronary Artery Disease (OXBIO Study)

Study Overview
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Brief Summary
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The purpose of this study is to determine the effect of 6R-BH4 on vascular function in patients with coronary artery disease. We hypothesize that 6R-BH4 will improve vascular function in these patients.

Detailed Description
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Decreased production of nitric oxide (NO) from the endothelium (the layer of cells that forms the lining of all blood vessels) has been shown to contribute to atherosclerosis. NO has multiple beneficial effects on vascular function. Endothelial function can be measured in humans via a number of methods, and endothelial dysfunction has been shown to be a strong adverse predictor of cardiovascular events and mortality. Tetrahydrobiopterin (BH4) is essential for the production of NO in endothelial cells. 6R-BH4 is a synthetic version of naturally occurring BH4. We aim to investigate the effects of oral 6R-BH4 supplementation on endothelial function in patients with coronary artery disease.

Official Title
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A Randomised, Placebo-Controlled Study of Two Doses of Oral 6R-BH4 on Vascular Function in Subjects With Coronary Artery Disease

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: 6R-BH4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Multi-vessel coronary artery disease scheduled for coronary artery bypass surgery (CABG) Exclusion Criteria: Inability to provide informed consent Female subject who is pregnant, lactating or planning pregnancy during course of study Prior clinical diagnosis of heart failure requiring diuretic therapy with evidence of severe left ventricular dysfunction Recent acute coronary event (<4 weeks) Emergency CABG Newly diagnosed diabetes mellitus (<1 month) Body weight >130kg Impaired renal function (creatinine >180umol/l) Elevated liver function tests (ALT >50umol/l or AST >2x normal) Pacemakers, ICDs or metallic implants not compatible with MRI scanning Subjects receiving experimental medications or participating in another study Terminally ill subjects Known hypersensitivity to 6R-BH4 Concomitant treatment with methotrexate, levodopa, PDE-3 or PDE-5 inhibitors

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>700mg/day 6R-BH4 | Drug: 6R-BH4<br>* 6R-BH4 tablets 700mg/day, 6R-BH4 tablets 400mg/day or placebo<br>* Other names: Sapropterin dihydrochloride;|
| Active Comparator: 2<br>400mg/day 6R-BH4 | Drug: 6R-BH4<br>* 6R-BH4 tablets 700mg/day, 6R-BH4 tablets 400mg/day or placebo<br>* Other names: Sapropterin dihydrochloride;|
| Placebo Comparator: 3<br>Placebo | Drug: 6R-BH4<br>* 6R-BH4 tablets 700mg/day, 6R-BH4 tablets 400mg/day or placebo<br>* Other names: Sapropterin dihydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular function using non-invasive magnetic resonance imaging (MRI). |  | Pre- and post- treatment with 6R-BH4 or placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laboratory measures of vascular function. |  | At time of CABG surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endothelium, Nitric Oxide, Magnetic Resonance Imaging, Tetrahydrobiopterin