Endothelial DysfunctionACOVANCT01162824
Blood Markers for Inflammation and Coronary Artery Vasoreactivity Testing in Patients With Chest Pain and Normal Coronary Arteries
A study testing Acetylcholine and Adenosine in people with Endothelial Dysfunction and Atherosclerosis, run by St George's Healthcare NHS Trust at 1 site in United Kingdom.
Trial summary
The investigators are hoping to discover the cause of chest pain in patients with a normal coronary arteriogram. For patients with chest pain coronary angiography is the standard method by which the blood vessels of the heart can be visualized and any narrowing can be assessed. Read more about this study
- Who is it for?
- Ages 35 years and older
- Conditions the study is for
- Endothelial Dysfunction, Atherosclerosis, Inflammation
- What is being tested?
- Acetylcholine and Adenosine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2011to Dec 2011
- Phase
- Interventional
- 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 35 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults of either gender > 35 years of age with a stable pattern of angina pectoris suggestive of coronary artery disease, with positive responses to exercise stress testing AND/OR patients with chest pain and ischaemic ST-segment changes during pain (previous obstructive coronary artery disease with or without stent-implantation will be allowed).
- Subjects will be invited to participate only if investigations have been undertaken to rule out non-cardiac causes for chest pain (i.e. oesophageal and musculoskeletal) previously.
- Serum creatinine < 123.7µmol/L.
- Left ventricular ejection fraction > 50%.
Who cannot join
- Chronic obstructive pulmonary disease.
- Cardiomyopathy.
- Severe valvular heart disease.
- Myocardial infarction within the last 3 months.
- Pregnant or lactating women.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Department of Cardiology, St George's Healthcare NHS Trust
London, England, SW17 0RE
Peter E Ong, MD, +44208725 ext. 2628, pong@sgul.ac.uk
Peter E Ong, MD
About this study
Official title: Correlation Between Abnormal Coronary Vasoreactivity Testing, Expansion of CD4+CD28null T Cells and Biomarkers for Inflammation and Endothelial Dysfunction in Patients With Angina Despite Angiographically Normal Coronary Arteries.
The investigators are hoping to discover the cause of chest pain in patients with a normal coronary arteriogram. For patients with chest pain coronary angiography is the standard method by which the blood vessels of the heart can be visualized and any narrowing can be assessed. In some cases the investigators find totally normal coronary blood vessels or only minor disease. Such a finding is associated with an excellent long term prognosis. However, as a large proportion of patients with normal coronary arteries or mild coronary narrowings often continue to experience recurrent chest pains the investigators are interested in understanding the mechanisms responsible for this. The investigators hypothesise that in many cases, coronary artery spasms are responsible for the recurrent chest pains. These spasms usually respond to treatment with drugs known as vasodilators. The acetylcholine test (ACH-test) has been recommended by the European Society of Cardiology and the American College of Cardiology as a diagnostic test. This test can reveal whether the coronary blood vessels have a tendency to go into spasm. The investigators plan in this study to carry out the test in patients who have chest pains suggestive of coronary narrowings but are found to have normal or only mildly narrowed coronary arteries on angiography. A positive test -indicating a tendency for spasm- may help guiding therapy with vasodilators, which are often very effective to prevent coronary spasms. The investigators would also like to take blood samples during the test (before and after) from every patient to measure blood markers and see if there is a relation between these markers and the result of the ACH-test.
Read the detailed description
This study comprises two parts:
- Blood sample
- ACH-test (including coronary flow measurements)
Blood will be taken, frozen and stored for up to 5 years. The following markers will be studied: C-reactive protein, E-selectin, neopterin, troponin and CD40 ligand. These are essential biochemical markers or so called pro-inflammatory substances that normally circulate in the blood but their levels can increase under certain conditions such as stress or inflammation. In addition, expansion of CD4+CD28null T-cells will be measured via flow cytometry.
Coronary angiography will be performed according to routine clinical guidelines. If the investigators find severe disease standard treatment procedures will take place and the investigators will only ask for a blood sample. If the investigators find normal coronary arteries on coronary angiography the investigators will conduct the ACH-test as part of the study. After injecting ACH into the coronary arteries narrowing can occur and provoke the same or similar symptoms as at home (i.e. chest pain). If you experience severe pain the investigators will inject a drug called nitroglycerine to relieve the pain. Then the investigators will measure the capacity of the blood vessels to dilate with a special catheter. The whole procedure including coronary angiography and ACH-test will last for about one hour. There is only very little radiation needed for the ACH-test which is unlikely to cause any health problems (~2.4mSv). In some very rare cases chest pain can be prolonged and heart rhythm disorders can occur. In worst case prolonged narrowing can lead to a heart attack (myocardial infarction, < 1%).
The result of the ACH-test can lead to 3 different results.
- Epicardial coronary spasm. This means that the narrowing of the blood vessel occurs in a place where it can be seen on the screen during angiography.
- Microvascular dysfunction This means that the narrowing of the blood vessel cannot be seen on the screen but on the ECG. It only affects the very small blood vessels of the heart.
- Normal ACH-test This means that the test is normal and the patient has no chest pain during the test and also no narrowing.
Depending on the result the investigators will suggest to start with a medication according to current guidelines and inform the patient's GP about the results and further suggestions for treatment. To maintain confidentiality all participants are entered onto our secure database using only their initials and a study number.
- Being tested
- Acetylcholine, Adenosine
- Keywords
- Endothelial Dysfunction, Microvascular dysfunction, Coronary artery spasm, Inflammation, CD4+CD28null T cells, Myocardial ischemia, Early atherosclerosis
- Medical subject headings
- Atherosclerosis, Inflammation, Myocardial Ischemia, Coronary Vasospasm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetylcholineDrug
Also called Acetylcholine will be used from Miochol-E (Novartis)
Incremental doses of 2, 20 and 100 µg of ACH will be injected into the left coronary artery (LCA) via the diagnostic catheter for 3 minutes each. After that 80 µg of ACH will be injected into the right coronary artery. Coronary angiography will be performed after each 3 minute dose period. After the test or when intolerable chest pain due to coronary spasm occurs, 0.2 mg of glyceryltrinitrate will be injected into each vessel. During the test, heart rate, blood pressure and ECG will be monitored continuously.
AdenosineDrug
Coronary blood flow velocity measurements will be performed in the mid segment of the left anterior descending artery with a 0.014-in intracoronary Doppler guidewire connected to the corresponding interface. Measurements will be obtained after the administration of nitroglycerin, at baseline and during maximal hyperaemia. Sustained intravenous administration of adenosine - an arteriolar vasodilator- will be used to induce maximal hyperaemia (140-180µg/kg/min).
| Study group | Role | What they receive |
|---|---|---|
| No endothelial dysfunction | Other | Not described Receives: Drug: Acetylcholine; Drug: Adenosine |
| Endothelial Dysfunction | Other | Definition of abnormal epicardial and microvascular vasoreactivity Abnormal epicardial vasoreactivity is defined as a reduction of the baseline coronary diameter ≥75% after glyceryltrinitrate i.c. together with a reproduction of the angina symptoms reported by the patient and/or ischemic ECG-changes. Abnormal microvascular vasoreactivity is defined as the reproduction of the angina symptoms together with ischaemic ECG-changes, but without changes in epicardial vasomotion. Receives: Drug: Acetylcholine; Drug: Adenosine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endothelial Dysfunction
As this is not a follow-up study, the intracoronary vasoreactivity tests will be conducted at the day of study entry to assess which patient suffers from endothelial dysfunction. According to this result the patients will be divided into two groups (endothelial dysfunction and NO endothelial dysfunction).
Definition of endothelial dysfunction:
Vasoconstriction of >75% together with ischemic ECG changes and/or reproduction of angina OR ischemic ECG changes with reproduction of angina without vasoconstriction
Measured: Day 1 (day of study entry)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2010 (estimated)
- Study startJan 2011
- Primary completionApr 2011 (estimated)
- Study completionDec 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endothelial DysfunctionStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St George's Healthcare NHS Trust
- Sponsor type
- University, hospital or other
- Investigators
- Juan C Kaski, MD, Principal investigator, Department of Cardiology, St George's Healthcare NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01162824
- Sponsor's protocol ID
- ACOVA-8
- Acronym
- ACOVA
- Status last verified
- Feb 2011
- First submitted
- 13 Jul 2010
- Last updated
- 23 Feb 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Correlation Between Abnormal Coronary Vasoreactivity Testing, Expansion of CD4+CD28null T Cells and Biomarkers for Inflammation and Endothelial Dysfunction in Patients With Angina Despite Angiographically Normal Coronary Arteries.
- ClinicalTrials.gov ID
- NCT01162824
- Acronym / sponsor ID
- ACOVA / ACOVA-8
- Keywords
- Endothelial Dysfunction, Microvascular dysfunction, Coronary artery spasm, Inflammation, CD4+CD28null T cells, Myocardial ischemia, Early atherosclerosis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- St George's Healthcare NHS TrustUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Apr 2011 (estimated)
- Study completion
- Dec 2011 (estimated)
- First posted
- 15 Jul 2010 (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 investigators are hoping to discover the cause of chest pain in patients with a normal coronary arteriogram. For patients with chest pain coronary angiography is the standard method by which the blood vessels of the heart can be visualized and any narrowing can be assessed. In some cases the investigators find totally normal coronary blood vessels or only minor disease. Such a finding is associated with an excellent long term prognosis. However, as a large proportion of patients with normal coronary arteries or mild coronary narrowings often continue to experience recurrent chest pains the investigators are interested in understanding the mechanisms responsible for this. The investigators hypothesise that in many cases, coronary artery spasms are responsible for the recurrent chest pains. These spasms usually respond to treatment with drugs known as vasodilators. The acetylcholine test (ACH-test) has been recommended by the European Society of Cardiology and the American College of Cardiology as a diagnostic test. This test can reveal whether the coronary blood vessels have a tendency to go into spasm. The investigators plan in this study to carry out the test in patients who have chest pains suggestive of coronary narrowings but are found to have normal or only mildly narrowed coronary arteries on angiography. A positive test -indicating a tendency for spasm- may help guiding therapy with vasodilators, which are often very effective to prevent coronary spasms. The investigators would also like to take blood samples during the test (before and after) from every patient to measure blood markers and see if there is a relation between these markers and the result of the ACH-test.
Detailed description
This study comprises two parts:
- Blood sample
- ACH-test (including coronary flow measurements)
Blood will be taken, frozen and stored for up to 5 years. The following markers will be studied: C-reactive protein, E-selectin, neopterin, troponin and CD40 ligand. These are essential biochemical markers or so called pro-inflammatory substances that normally circulate in the blood but their levels can increase under certain conditions such as stress or inflammation. In addition, expansion of CD4+CD28null T-cells will be measured via flow cytometry.
Coronary angiography will be performed according to routine clinical guidelines. If the investigators find severe disease standard treatment procedures will take place and the investigators will only ask for a blood sample. If the investigators find normal coronary arteries on coronary angiography the investigators will conduct the ACH-test as part of the study. After injecting ACH into the coronary arteries narrowing can occur and provoke the same or similar symptoms as at home (i.e. chest pain). If you experience severe pain the investigators will inject a drug called nitroglycerine to relieve the pain. Then the investigators will measure the capacity of the blood vessels to dilate with a special catheter. The whole procedure including coronary angiography and ACH-test will last for about one hour. There is only very little radiation needed for the ACH-test which is unlikely to cause any health problems (~2.4mSv). In some very rare cases chest pain can be prolonged and heart rhythm disorders can occur. In worst case prolonged narrowing can lead to a heart attack (myocardial infarction, < 1%).
The result of the ACH-test can lead to 3 different results.
- Epicardial coronary spasm. This means that the narrowing of the blood vessel occurs in a place where it can be seen on the screen during angiography.
- Microvascular dysfunction This means that the narrowing of the blood vessel cannot be seen on the screen but on the ECG. It only affects the very small blood vessels of the heart.
- Normal ACH-test This means that the test is normal and the patient has no chest pain during the test and also no narrowing.
Depending on the result the investigators will suggest to start with a medication according to current guidelines and inform the patient's GP about the results and further suggestions for treatment. To maintain confidentiality all participants are entered onto our secure database using only their initials and a study number.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| No endothelial dysfunction | Other | Drug: Acetylcholine, Drug: Adenosine |
| Endothelial Dysfunction | Other | Drug: Acetylcholine, Drug: AdenosineDefinition of abnormal epicardial and microvascular vasoreactivity Abnormal epicardial vasoreactivity is defined as a reduction of the baseline coronary diameter ≥75% after glyceryltrinitrate i.c. together with a reproduction of the angina symptoms reported by the patient and/or ischemic ECG-changes. Abnormal microvascular vasoreactivity is defined as the reproduction of the angina symptoms together with ischaemic ECG-changes, but without changes in epicardial vasomotion. |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adults of either gender > 35 years of age with a stable pattern of angina pectoris suggestive of coronary artery disease, with positive responses to exercise stress testing AND/OR patients with chest pain and ischaemic ST-segment changes during pain (previous obstructive coronary artery disease with or without stent-implantation will be allowed).
- Subjects will be invited to participate only if investigations have been undertaken to rule out non-cardiac causes for chest pain (i.e. oesophageal and musculoskeletal) previously.
- Serum creatinine < 123.7µmol/L.
- Left ventricular ejection fraction > 50%.
Key exclusion criteria (5 listed)
- Chronic obstructive pulmonary disease.
- Cardiomyopathy.
- Severe valvular heart disease.
- Myocardial infarction within the last 3 months.
- Pregnant or lactating women.
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 |
|---|---|---|
| AcetylcholineAlso: Acetylcholine will be used from Miochol-E (Novartis)Incremental doses of 2, 20 and 100 µg of ACH will be injected into the left coronary artery (LCA) via the diagnostic catheter for 3 minutes each. After that 80 µg of ACH will be injected into the right coronary artery. Coronary angiography will be performed after each 3 minute dose period. After the test or when intolerable chest pain due to coronary spasm occurs, 0.2 mg of glyceryltrinitrate will be injected into each vessel. During the test, heart rate, blood pressure and ECG will be monitored continuously. | Drug | Endothelial Dysfunction, No endothelial dysfunction |
| AdenosineCoronary blood flow velocity measurements will be performed in the mid segment of the left anterior descending artery with a 0.014-in intracoronary Doppler guidewire connected to the corresponding interface. Measurements will be obtained after the administration of nitroglycerin, at baseline and during maximal hyperaemia. Sustained intravenous administration of adenosine - an arteriolar vasodilator- will be used to induce maximal hyperaemia (140-180µg/kg/min). | Drug | Endothelial Dysfunction, No endothelial dysfunction |
Primary outcome
Endothelial Dysfunction
Time frame: Day 1 (day of study entry)
As this is not a follow-up study, the intracoronary vasoreactivity tests will be conducted at the day of study entry to assess which patient suffers from endothelial dysfunction. According to this result the patients will be divided into two groups (endothelial dysfunction and NO endothelial dysfunction). Definition of endothelial dysfunction: Vasoconstriction of >75% together with ischemic ECG changes and/or reproduction of angina OR ischemic ECG changes with reproduction of angina without vasoconstriction
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2011.
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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.
Juan C Kaski, MD principal investigator
Department of Cardiology, St George's Healthcare NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acetylcholine and Adenosine in people with Endothelial Dysfunction and Atherosclerosis, run by St George's Healthcare NHS Trust 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 4 inclusion and 5 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 23 Feb 2011. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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 Peter E Ong, MD (+44208725 ext. 2628, pong@sgul.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endothelial Dysfunction (time frame: Day 1 (day of study entry)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Feb 2011.