An observational study in Ischemic Heart Disease, Microvascular Coronary Artery Disease and Depression, sponsored by Instituto de Salud Carlos III. Status unknown at 1 site in Spain. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-01-06.
Sponsored by Instituto de Salud Carlos III · Observational
This is a prospective cohort blinded study with the aim to investigate the prevalence and clinical impact of coronary microcirculatory dysfunction (CMD) in patients with ischemic heart disease, and its association with cerebral small vessel disease (CSVD) and depressive disorders. In addition, CMD and CSVD linkage to systemic inflammation and endothelial function will also be investigated.
The treatment of stable CAD is largely based on a paradigm that gives epicardial coronary stenoses a central role in the generation of myocardial ischaemia. However, coronary microcirculatory dysfunction (CMD) is a major and frequently ignored cause of ischaemia that, according to retrospective studies, influences the outcomes of patients with CAD. In addition, patients with CMD may not experience symptomatic relief with myocardial revascularization or pharmacological treatment. This constitutes one of the causes of persistent angina despite successful revascularization, causing not only an impairment of the quality of life and higher consumption of healthcare resources, but potentially affective disorders like depression, which has been found to be associated with CAD and with prognosis.
It also remains largely unknown whether CMD in stable CAD is organ-specific only or rather indicative of involvement of other vital organs. While this seems to be the case in the kidney and the retina, the relationship between CMD in the heart and the brain has not been studied. Beyond classical cardiovascular risk factors linked to the development of ischemic heart disease, systemic endothelial dysfunction could constitute a link between microcirculatory involvement in both organs: the heart and the brain. Additionally, the relation between chronic inflammatory status and microvascular disease in both the heart and the brain is not known.
The principal hypotheses and sub-hypotheses are as follows:
Principal hypotheses: 1. Patients with CMD have worse prognosis compared to those ones with normal coronary microcirculation. 2. Patients with CMD have a higher prevalence of CSVD. 3. Chronic systemic inflammation status is an independent predictor of CMD and CSVD.
Sub-hypotheses: 1. The presence of CMD is associated to recurrent/persistent angina. 2. The presence of CMD is associated to higher prevalence of depressive disorders. 3. CMD and CSVD are associated to systemic endothelial dysfunction.
Primary Objectives associated to Principal hypotheses: 1. To investigate the relationship between the presence of CMD and the development of patient-focused outcomes at 1 year of follow-up. 2. To determine the prevalence of CSVD in patients with CAD with and without CMD. 3. To investigate the relationship between systemic inflammation and CMD.
Primary Objectives associated to Sub-hypotheses: 1. To determine the prevalence of persistent or recurrent angina in patients with and without CMD in whom revascularization of CAD is guided by FFR. 2. To determine the prevalence of depressive disorders in patients with and without CMD. 3. To investigate the relationship between the status of systemic endothelial function and the presence of CMD and CSVD.
Methods: Patients with CAD undergoing FFR-guided revascularisation will be prospectively enrolled. FFR, coronary flow reserve (CFR) and the index of hyperemic microvascular resistance (HMR) will be measured with the Doppler guidewire (Combowire, Volcano - Philips corporation) under steady state hyperemia (intravenous adenosine infusion, 140 mcg/Kg/min). CMD will be defined according to CFR and HMR, and will be used to classify the overall population in two groups: the study group (presence of CMD) and the control group (absence of CMD). Coronary revascularization will be decided according to result of FFR (cutoff ≤0.80).
After the procedure the patient will undergo baseline clinical assessment: • Neurological clinical assessment and Transcranial Doppler Ultrasound. • Psychiatric clinical assessment. • Stress Cardiac MRI and Cerebral MRI. • Peripheral endothelial function test with plethysmography-based device EndoPat. • Laboratory blood tests for systemic inflammation markers, platelet function and endothelial progenitor cells. • Baseline assessment of angina status by the Seattle Questionnaire of angina (SAQ).
Clinical follow-up will be performed at 1-month, 6-months and 1-year, and will include: • clinical cardiology and psychiatric assessment, assessment of angina status by the SAQ. • stress test (1-year). • peripheral endothelial function test with plethysmography-based device EndoPat (1-year). • neurological clinical assessment and Transcranial Doppler Ultrasound (1- year). • laboratory blood tests for systemic inflammation markers, platelets function and endothelial progenitor cells(1-year).
Type of blinding: Data regarding coronary microcirculation invasive assessment, neurologic and psychiatric clinical assessment, cardiac and cerebral MRI, Trans-cranial Doppler Ultrasound, laboratory blood tests, systemic endothelial function and follow-up will be collected in a blinded fashion, so that patient and the other investigators, apart from the invasive cardiology team responsible for patient enrollment and study coordination, could not access to them. Primary events rate (major adverse cardiovascular events, incidence of CSVD, systemic inflammation status, depressive disorders, recurrent angina and systemic endothelial dysfunction) will be analyzed and correlated to CMD in a blinded fashion.
1,123 studies on the registry are indexed under Myocardial Ischemia; 177 are open to participants now.
This study's planned enrollment of 100 is below the median of 318 across 398 observational studies indexed under Myocardial Ischemia.
Browse Myocardial Ischemia studies →Instituto de Salud Carlos III is the lead sponsor of 10 studies on the registry; 3 are open to participants now.
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Patients with stable coronary lesions (stable coronary disease or lesions in non-culprit vessels >48 hours after acute coronary syndrome) with clinical indication to coronary angiography and intermediate coronary lesions (visual estimation) suitable for FFR-guided revascularization.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with CAD undergoing FFR-guided revascularisation. FFR, coronary flow reserve (CFR) and the index of hyperemic microvascular resistance (HMR) will be measured with the Doppler guidewire (Combowire, Volcano - Philips corporation) under steady state hyperemia.
Procedure: Coronary Angiography and Multimodal Coronary Physiology Study (FFR, CFR, HMR)
Coronary Angiography according to clinical indication and Multimodal Coronary Physiology Study (FFR, CFR, HMR) for functional assessment of intermediate coronary lesions
Incidence of Major Cardiovascular Events (MACE): all-cause of death, myocardial infarction and any type of coronary revascularization
Clinical assessment
Time frame: 1 month
Incidence of Major Cardiovascular Events (MACE): all-cause of death, myocardial infarction and any type of coronary revascularization
Clinical assessment.
Time frame: 6 months
Incidence of Major Cardiovascular Events (MACE): all-cause of death, myocardial infarction and any type of coronary revascularization
Clinical assessment.
Time frame: 1 year
Prevalence of Cerebral Small Vessel Disease (CSVD).
Determined by Cerebral MRI, transcranial Doppler Ultrasound and clinical assessment.
Time frame: Baseline
Prevalence of Cerebral Small Vessel Disease (CSVD).
Determined by Cerebral MRI, transcranial Doppler Ultrasound and clinical assessment.
Time frame: 1 year
Assessment of angina status by Seattle Angina Questionnaire (SAQ)
The SAQ (Seattle Angina Questionnaire) quantifies 5 domains measuring the impact of angina on patients' health status: Physical Limitation (9 items), Angina Stability (1 item), Angina Frequency (2 items), Treatment Satisfaction (4 items), and Quality of Life (3 items). Item responses are coded sequentially from worst to best status and range from 1 to 6 for Physical Limitation, Angina Stability, and Angina Frequency items; 1 to 5/6 for Treatment Satisfaction items; and 1 to 5 for Quality of Life items. Scores are generated for each domain and are scaled 0 to 100, with 0 denoting the worst and 100 the best possible status.
Time frame: 1 month
Assessment of angina status by Seattle Angina Questionnaire (SAQ)
The SAQ (Seattle Angina Questionnaire) quantifies 5 domains measuring the impact of angina on patients' health status: Physical Limitation (9 items), Angina Stability (1 item), Angina Frequency (2 items), Treatment Satisfaction (4 items), and Quality of Life (3 items). Item responses are coded sequentially from worst to best status and range from 1 to 6 for Physical Limitation, Angina Stability, and Angina Frequency items; 1 to 5/6 for Treatment Satisfaction items; and 1 to 5 for Quality of Life items. Scores are generated for each domain and are scaled 0 to 100, with 0 denoting the worst and 100 the best possible status.
Time frame: 6 months
Assessment of angina status by Seattle Angina Questionnaire (SAQ)
The SAQ (Seattle Angina Questionnaire) quantifies 5 domains measuring the impact of angina on patients' health status: Physical Limitation (9 items), Angina Stability (1 item), Angina Frequency (2 items), Treatment Satisfaction (4 items), and Quality of Life (3 items). Item responses are coded sequentially from worst to best status and range from 1 to 6 for Physical Limitation, Angina Stability, and Angina Frequency items; 1 to 5/6 for Treatment Satisfaction items; and 1 to 5 for Quality of Life items. Scores are generated for each domain and are scaled 0 to 100, with 0 denoting the worst and 100 the best possible status.
Time frame: 1 year
Prevalence of depressive and anxiety disorders, determined by clinical assessment and dedicated questionnaires.
An expert psychologist will perform the following assessment: i) basal depression screening (Patient Health Questionnaire \[PHQ-9\]); ii) Standardized Interview (International neuropsychiatric interview) iii) evaluation of the severity of depression (Montgomery-Asberg score \[MDRS\]); iv) anxiety symptoms detection (Hamilton anxiety rating scale \[HARS\]); v) assessment of baseline quality of life (The MOS 36-item Short Form Health Survey \[SF-36\]); vi) functional skills assessment (The Lawton Instrumental Activities of Daily Living (IADL) Scale).
Time frame: 1 month
Prevalence of depressive and anxiety disorders, determined by clinical assessment and dedicated questionnaires.
An expert psychologist will perform the following assessment: i) basal depression screening (Patient Health Questionnaire \[PHQ-9\]); ii) Standardized Interview (International neuropsychiatric interview) iii) evaluation of the severity of depression (Montgomery-Asberg score \[MDRS\]); iv) anxiety symptoms detection (Hamilton anxiety rating scale \[HARS\]); v) assessment of baseline quality of life (The MOS 36-item Short Form Health Survey \[SF-36\]); vi) functional skills assessment (The Lawton Instrumental Activities of Daily Living (IADL) Scale).
Time frame: 6 months
Prevalence of depressive and anxiety disorders, determined by clinical assessment and dedicated questionnaires.
An expert psychologist will perform the following assessment: i) basal depression screening (Patient Health Questionnaire \[PHQ-9\]); ii) Standardized Interview (International neuropsychiatric interview) iii) evaluation of the severity of depression (Montgomery-Asberg score \[MDRS\]); iv) anxiety symptoms detection (Hamilton anxiety rating scale \[HARS\]); v) assessment of baseline quality of life (The MOS 36-item Short Form Health Survey \[SF-36\]); vi) functional skills assessment (The Lawton Instrumental Activities of Daily Living (IADL) Scale).
Time frame: 1 year
Prevalence of systemic inflammation status, determined by laboratory blood tests.
Determination of blood levels of pro-inflammatory proteins (hsCRP, IL-1, IL-6, IL-18, VCAM-1 and ICAM-1) by ELISA method. Given the fact that the chronic inflammation can induce changes in the mononuclear cells phenotype, we will analyze the immune activation status (by analyzing CD4+/CD38+-T lymphocytes, CD8+/CD38+-T lymphocytes and CD8+/CD38+/HLADR+-T lymphocytes). The analysis will be performed by flow cytometry (Galios, Beckman Coulter). In addition, we will study the NRLP3 protein complex (which is involved in atherogenesis).
Time frame: Baseline
Prevalence of systemic inflammation status, determined by laboratory blood tests.
Determination of blood levels of pro-inflammatory proteins (hsCRP, IL-1, IL-6, IL-18, VCAM-1 and ICAM-1) by ELISA method. Given the fact that the chronic inflammation can induce changes in the mononuclear cells phenotype, we will analyze the immune activation status (by analyzing CD4+/CD38+-T lymphocytes, CD8+/CD38+-T lymphocytes and CD8+/CD38+/HLADR+-T lymphocytes). The analysis will be performed by flow cytometry (Galios, Beckman Coulter). In addition, we will study the NRLP3 protein complex (which is involved in atherogenesis).
Time frame: 1 year
Peripheral endothelial dysfunction, assessed by EndoPat.
Systemic endothelial dysfunction is defined as the inability of the arterial system to dilate appropriately in response to hyperaemia stimulus in order to increase blood flow according to metabolic demands. In this study, we will use the EndoPat technology that allows non-invasive evaluation of vasoreactivity by the assessment of the pulsatile arterial flow in the fingertip. We will assess changes in the flow from baseline and after inducing ischaemia by inflating a blood pressure cuff to occlude the brachial artery. Changes in endothelial measurements and in vascular tone after each occlusion of the brachial artery are a reflection of the hyperaemic vasoreactivity and endothelial function. By comparing the results during rest and ischaemia to the results obtained in the contralateral arm (which has not been subjected to ischaemia) we will obtain the index of reactive hyperaemia or EndoScore´. This Endoscore can then be used to evaluate endothelial function.
Time frame: Baseline
Peripheral endothelial dysfunction, assessed by EndoPat.
Systemic endothelial dysfunction is defined as the inability of the arterial system to dilate appropriately in response to hyperaemia stimulus in order to increase blood flow according to metabolic demands. In this study, we will use the EndoPat technology that allows non-invasive evaluation of vasoreactivity by the assessment of the pulsatile arterial flow in the fingertip. We will assess changes in the flow from baseline and after inducing ischaemia by inflating a blood pressure cuff to occlude the brachial artery. Changes in endothelial measurements and in vascular tone after each occlusion of the brachial artery are a reflection of the hyperaemic vasoreactivity and endothelial function. By comparing the results during rest and ischaemia to the results obtained in the contralateral arm (which has not been subjected to ischaemia) we will obtain the index of reactive hyperaemia or EndoScore´. This Endoscore can then be used to evaluate endothelial function.
Time frame: 1 year
Plan to share: No
This study is status unknown, as verified in Jan 2020. You cannot join it, but the record below documents what was studied.
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Instituto de Salud Carlos III