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

Coronary Artery Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00423280
• Other study ID #: 06/Q1604/114
• Status: Recruiting
• Phase: Phase 2
• First received: January 17, 2007
• Last updated: August 6, 2008
• Start date: November 2006
• Est. completion date: February 2009

Study information

• Verified date: June 2008
• Source: University of Oxford
• Contact: Colin Cunnington, MBChB MRCP
• Phone: +44-1865-221866
• Email: colin.cunnington[@]cardiov.ox.ac.uk
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• 6R-BH4
6R-BH4 tablets 700mg/day, 6R-BH4 tablets 400mg/day or placebo

Locations

Country	Name	City	State
United Kingdom	Department of Cardiovascular Medicine, University of Oxford	Oxford

Sponsors (2)

Lead Sponsor	Collaborator
University of Oxford	BioMarin Pharmaceutical

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vascular function using non-invasive magnetic resonance imaging (MRI).		Pre- and post- treatment with 6R-BH4 or placebo	No
Secondary	Laboratory measures of vascular function.		At time of CABG surgery	No