Coronary Artery DiseasePhase 2NCT00423280
Effect of 6R-BH4 Treatment in Coronary Artery Disease (OXBIO Study)
A Phase 2 study testing 6R-BH4 in people with Coronary Artery Disease, run by University of Oxford at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- 6R-BH4
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2006to Feb 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Multi-vessel coronary artery disease scheduled for coronary artery bypass surgery (CABG)
Who cannot join
- 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)
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Department of Cardiovascular Medicine, University of Oxford
Oxford, OX3 9DU
About this study
Official title: A Randomised, Placebo-Controlled Study of Two Doses of Oral 6R-BH4 on Vascular Function in Subjects With Coronary Artery Disease
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.
Read the 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.
- Conditions
- Coronary Artery Disease
- Being tested
- 6R-BH4
- Keywords
- Endothelium, Nitric Oxide, Magnetic Resonance Imaging, Tetrahydrobiopterin
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
6R-BH4Drug
Also called Sapropterin dihydrochloride
6R-BH4 tablets 700mg/day, 6R-BH4 tablets 400mg/day or placebo
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | 700mg/day 6R-BH4 Receives: Drug: 6R-BH4 |
| 2 | Active comparator | 400mg/day 6R-BH4 Receives: Drug: 6R-BH4 |
| 3 | Placebo comparator | Placebo Receives: Drug: 6R-BH4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vascular function using non-invasive magnetic resonance imaging (MRI).
Measured: Pre- and post- treatment with 6R-BH4 or placebo
Secondary outcomes (1)
Laboratory measures of vascular function.
Measured: At time of CABG surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2007 (estimated)
- Study startNov 2006
- Primary completionFeb 2009 (estimated)
- Study completionFeb 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Investigators
- Keith M Channon, MD FRCP, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00423280
- Sponsor's protocol ID
- 06/Q1604/114
- Status last verified
- Jun 2008
- First submitted
- 17 Jan 2007
- Last updated
- 7 Aug 2008
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 22315282Cunnington 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.
PubMed 20837663
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Placebo-Controlled Study of Two Doses of Oral 6R-BH4 on Vascular Function in Subjects With Coronary Artery Disease
- ClinicalTrials.gov ID
- NCT00423280
- Acronym / sponsor ID
- 06/Q1604/114
- Conditions
- Coronary Artery Disease
- Keywords
- Endothelium, Nitric Oxide, Magnetic Resonance Imaging, Tetrahydrobiopterin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- BioMarin Pharmaceutical
- Study start
- Nov 2006
- Primary completion
- Feb 2009 (estimated)
- Study completion
- Feb 2009 (estimated)
- First posted
- 18 Jan 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: 6R-BH4700mg/day 6R-BH4 |
| 2 | Active comparator | Drug: 6R-BH4400mg/day 6R-BH4 |
| 3 | Placebo comparator | Drug: 6R-BH4Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Multi-vessel coronary artery disease scheduled for coronary artery bypass surgery (CABG)
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 6R-BH4Also: Sapropterin dihydrochloride6R-BH4 tablets 700mg/day, 6R-BH4 tablets 400mg/day or placebo | Drug | 1, 2, 3 |
Primary outcome
Vascular function using non-invasive magnetic resonance imaging (MRI).
Time frame: Pre- and post- treatment with 6R-BH4 or placebo
1 secondary outcome
Laboratory measures of vascular function.
Time frame: At time of CABG surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2008.
- Derived from this study: PubMed 22315282Cunnington 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.
- Derived from this study: PubMed 20837663Cunnington 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keith M Channon, MD FRCP principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 6R-BH4 in people with Coronary Artery Disease, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Aug 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Colin Cunnington, MBChB MRCP (+44-1865-221866, colin.cunnington@cardiov.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Vascular function using non-invasive magnetic resonance imaging (MRI). (time frame: Pre- and post- treatment with 6R-BH4 or placebo). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00423280, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2008.