Effect of 6R-BH4 Treatment in Coronary Artery Disease (OXBIO Study)
Primary Purpose
Coronary Artery Disease
Status
Unknown status
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
6R-BH4
Sponsored by
About this trial
This is an interventional treatment trial for Coronary Artery Disease focused on measuring Endothelium, Nitric Oxide, Magnetic Resonance Imaging, Tetrahydrobiopterin
Eligibility Criteria
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
Sites / Locations
- Department of Cardiovascular Medicine, University of OxfordRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
1
2
3
Arm Description
700mg/day 6R-BH4
400mg/day 6R-BH4
Placebo
Outcomes
Primary Outcome Measures
Vascular function using non-invasive magnetic resonance imaging (MRI).
Secondary Outcome Measures
Laboratory measures of vascular function.
Full Information
NCT ID
NCT00423280
First Posted
January 17, 2007
Last Updated
August 6, 2008
Sponsor
University of Oxford
Collaborators
BioMarin Pharmaceutical
1. Study Identification
Unique Protocol Identification Number
NCT00423280
Brief Title
Effect of 6R-BH4 Treatment in Coronary Artery Disease (OXBIO Study)
Official Title
A Randomised, Placebo-Controlled Study of Two Doses of Oral 6R-BH4 on Vascular Function in Subjects With Coronary Artery Disease
Study Type
Interventional
2. Study Status
Record Verification Date
June 2008
Overall Recruitment Status
Unknown status
Study Start Date
November 2006 (undefined)
Primary Completion Date
February 2009 (Anticipated)
Study Completion Date
February 2009 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
University of Oxford
Collaborators
BioMarin Pharmaceutical
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease
Keywords
Endothelium, Nitric Oxide, Magnetic Resonance Imaging, Tetrahydrobiopterin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
66 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
700mg/day 6R-BH4
Arm Title
2
Arm Type
Active Comparator
Arm Description
400mg/day 6R-BH4
Arm Title
3
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
6R-BH4
Other Intervention Name(s)
Sapropterin dihydrochloride
Intervention Description
6R-BH4 tablets 700mg/day, 6R-BH4 tablets 400mg/day or placebo
Primary Outcome Measure Information:
Title
Vascular function using non-invasive magnetic resonance imaging (MRI).
Time Frame
Pre- and post- treatment with 6R-BH4 or placebo
Secondary Outcome Measure Information:
Title
Laboratory measures of vascular function.
Time Frame
At time of CABG surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Colin Cunnington, MBChB MRCP
Phone
+44-1865-221866
Email
colin.cunnington@cardiov.ox.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Keith M Channon, MD FRCP
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Cardiovascular Medicine, University of Oxford
City
Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
Individual Site Status
Recruiting
12. IPD Sharing Statement
Citations:
PubMed Identifier
22315282
Citation
Cunnington C, Van Assche T, Shirodaria C, Kylintireas I, Lindsay AC, Lee JM, Antoniades C, Margaritis M, Lee R, Cerrato R, Crabtree MJ, Francis JM, Sayeed R, Ratnatunga C, Pillai R, Choudhury RP, Neubauer S, Channon KM. Systemic and vascular oxidation limits the efficacy of oral tetrahydrobiopterin treatment in patients with coronary artery disease. Circulation. 2012 Mar 20;125(11):1356-66. doi: 10.1161/CIRCULATIONAHA.111.038919. Epub 2012 Feb 7.
Results Reference
derived
PubMed Identifier
20837663
Citation
Cunnington C, Channon KM. Tetrahydrobiopterin: pleiotropic roles in cardiovascular pathophysiology. Heart. 2010 Dec;96(23):1872-7. doi: 10.1136/hrt.2009.180430. Epub 2010 Sep 13.
Results Reference
derived
Learn more about this trial
Effect of 6R-BH4 Treatment in Coronary Artery Disease (OXBIO Study)
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