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The Cerebral-Coronary Connection (C3) Study (C3)

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ClinicalTrials.gov Identifier: NCT04131075
Recruitment Status : Recruiting
First Posted : October 18, 2019
Last Update Posted : October 18, 2019
Sponsor:
Collaborator:
Hospital San Carlos, Madrid
Information provided by (Responsible Party):
Javier Escaned, Hospital San Carlos, Madrid

Brief Summary:
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.

Condition or disease Intervention/treatment
Ischemic Heart Disease Microvascular Coronary Artery Disease Depression Endothelial Dysfunction Inflammation Procedure: Coronary Angiography and Multimodal Coronary Physiology Study (FFR, CFR, HMR)

  Show Detailed Description

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Microcirculatory Dysfunction in Stable Coronary Artery Disease: Relationship With Patient-focused Outcomes, Cereblar Small Vessel Disease and Depression.
Actual Study Start Date : March 1, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : March 31, 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Study group
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




Primary Outcome Measures :
  1. Incidence of Major Cardiovascular Events (MACE): all-cause of death, myocardial infarction and any type of coronary revascularization [ Time Frame: 1 month ]
    Clinical assessment

  2. Incidence of Major Cardiovascular Events (MACE): all-cause of death, myocardial infarction and any type of coronary revascularization [ Time Frame: 6 months ]
    Clinical assessment.

  3. Incidence of Major Cardiovascular Events (MACE): all-cause of death, myocardial infarction and any type of coronary revascularization [ Time Frame: 1 year ]
    Clinical assessment.

  4. Prevalence of Cerebral Small Vessel Disease (CSVD). [ Time Frame: Baseline ]
    Determined by Cerebral MRI, transcranial Doppler Ultrasound and clinical assessment.

  5. Prevalence of Cerebral Small Vessel Disease (CSVD). [ Time Frame: 1 year ]
    Determined by Cerebral MRI, transcranial Doppler Ultrasound and clinical assessment.


Secondary Outcome Measures :
  1. Assessment of angina status by Seattle Angina Questionnaire (SAQ) [ Time Frame: 1 month ]
    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.

  2. Assessment of angina status by Seattle Angina Questionnaire (SAQ) [ Time Frame: 6 months ]
    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.

  3. Assessment of angina status by Seattle Angina Questionnaire (SAQ) [ Time Frame: 1 year ]
    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.

  4. Prevalence of depressive and anxiety disorders, determined by clinical assessment and dedicated questionnaires. [ Time Frame: 1 month ]
    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).

  5. Prevalence of depressive and anxiety disorders, determined by clinical assessment and dedicated questionnaires. [ Time Frame: 6 months ]
    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).

  6. Prevalence of depressive and anxiety disorders, determined by clinical assessment and dedicated questionnaires. [ Time Frame: 1 year ]
    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).

  7. Prevalence of systemic inflammation status, determined by laboratory blood tests. [ Time Frame: Baseline ]
    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).

  8. Prevalence of systemic inflammation status, determined by laboratory blood tests. [ Time Frame: 1 year ]
    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).

  9. Peripheral endothelial dysfunction, assessed by EndoPat. [ Time Frame: Baseline ]
    Systemic endotelial 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 endotelial 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.

  10. Peripheral endothelial dysfunction, assessed by EndoPat. [ Time Frame: 1 year ]
    Systemic endotelial 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 endotelial 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
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.
Criteria

Inclusion Criteria:

  • Informed Consent available.
  • Age ≥ 18 years.
  • Stable coronary lesions.
  • Indication to FFR: ≥ 1 intermediate coronary lesion (40-80% diameter stenosis) in a principal/secondary vessel with ≥ 2 mm reference diameter.

Exclusion Criteria:

  • Previous myocardial infarction in the territory of distribution of the target vessel.
  • Coronary Left Main severe stenosis.
  • Aortic valve stenosis (moderate or severe) .
  • Severe left ventricle hypertrophy.
  • Left ventricle moderate systolic dysfunction (EF < 35%).
  • Contraindications to adenosine.
  • Previous CABG with permeable grafts.
  • Contraindication to stent implantation.
  • Severe anemia.
  • Coagulopathies or chronic anticoagulation.
  • Platelets < 75000 o > 700.000.
  • Previous stroke or intracranial hemorrhage.
  • Contraindication to MRI.
  • Chronic Renal Failure contraindicating gadolinium infusion during MRI: eGFR < 60 ml/min), hemodialysis, previous renal transplantation.
  • Pacemaker/ Implantable Cardioverter Device with contraindication to MRI.
  • Planned cardiac surgery.
  • Life expectancy < 2 years.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04131075


Contacts
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Contact: Hernan Mejia-Renteria, MD +34/913303438 hmejiarenteria@gmail.com
Contact: Carolina Espejo Paeres, MD +34/913303438 carolina.espejo.paeres@gmail.com

Locations
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Spain
Hospital Clínico San Carlos Recruiting
Madrid, Spain, 28040
Contact: Javier Escaned, MD, PhD    +34913303438    javier.escaned@salud.madrid.org   
Contact: Carolina Espejo, MD    +34913303438    carolina.espejo.paeres@gmail.com   
Principal Investigator: Javier Escaned, MD, PhD         
Principal Investigator: Hernán Mejía Rentería, MD         
Sub-Investigator: Carolina Espejo, MD         
Principal Investigator: Jorge Matías-Guiu Guía, MD, PhD         
Sub-Investigator: Jordi A Matías-Guiu Guía, MD, PhD         
Principal Investigator: Blanca Reneses Prieto, MD, PhD         
Principal Investigator: Petros Papadopoulos, PhD         
Principal Investigator: Juan Arrazola García, MD         
Principal Investigator: Leopoldo Perez de Isla, MD, PhD         
Principal Investigator: Dulcenombre Gomez-Garre, MD, PhD         
Sub-Investigator: Ana Gomez-Ituiño, MSc         
Sub-Investigator: Ana Bustos, MD         
Sub-Investigator: Miguel Yus, MD         
Sub-Investigator: Josde Juan Gómez de Diego, MD         
Sponsors and Collaborators
Instituto de Salud Carlos III
Hospital San Carlos, Madrid
Investigators
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Principal Investigator: Javier Escaned, MD, PhD Instituto Carlos III. Hospital Clínico San Carlos.

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Responsible Party: Javier Escaned, MD, PhD, Hospital San Carlos, Madrid
ClinicalTrials.gov Identifier: NCT04131075     History of Changes
Other Study ID Numbers: C3
First Posted: October 18, 2019    Key Record Dates
Last Update Posted: October 18, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Javier Escaned, Hospital San Carlos, Madrid:
Coronary microvascular dysfunction
Cerebral Small Vessel Diseases
Additional relevant MeSH terms:
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Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Inflammation
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Pathologic Processes
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases