Back to resultsLinking Cardiac Autonomic Dysfunction and InfLammation in Patients With Acute Coronary Syndromes (CADILACS)
Primary Purpose
Acute Coronary Syndrome, Myocardial Ischemia
Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Anamnesis and clinical evaluation
Sponsored by
About this trial
This is an interventional diagnostic trial for Acute Coronary Syndrome focused on measuring Subclinical inflammation, Autonomic nervous system, Coronary Syndrome
Eligibility Criteria
Inclusion Criteria: Age ≥18 years; Evidence of previous complete percutaneous revascularization; ACS, with or without CAD, experienced in the previous 3 months ±15 days; Signed written informed consent. Exclusion Criteria: History of previous acute myocardial infarction (AMI); Prior surgical myocardial revascularization via coronary artery bypass graft (CABG); Previous incomplete percutaneous myocardial revascularization, as indicated by documentation of residual stenosis >50% or FFR ≤0.8 in any epicardial vessel; Killip class III-IV in admission; Established cardiovascular disease (assessed by clinical evaluation, physical exam, 12-lead ECG, or transthoracic echocardiogram), such as congenital heart disease, cardiomyopathy, and severe valvular heart disease; Serious medical conditions, including severe renal insufficiency (eGFR > 30 ml/min), hepatic insufficiency or cirrhosis, malignancies, COPD (GOLD stage III-IV), and acute or chronic inflammatory diseases; Refusal to sign the written informed consent to participate in the study.
Sites / Locations
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS di RomaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Partecipants with ACS and obstructive CAD
Partecipants with ACS without CAD, in a 1:1 ratio
Arm Description
The study is to identify a difference in the correlation between HRV and CRP parameters in ACS patients with or without obstructive CAD
Evaluate whether cardiac autonomic dysfunction is associated with low-grade systemic inflammation, inflammasome-dependent activation of IL-18 and IL-1β, and Th1/Treg frequency, in patients with ACS with or without obstructive CAD on angiography
Outcomes
Primary Outcome Measures
The correlation between HRV and CRP parameters in ACS patients with obstructive CAD
The primary endpoint of the study is to identify a difference in the correlation between HRV and CRP parameters in ACS patients with or without obstructive CAD.
This study will be performed through a detailed history and clinical evaluation based on transthoracic Doppler echocardiography (TTDE) and 24-hour Holter ECG recording.
The correlation between HRV and CRP parameters in ACS patients without obstructive CAD
The study is important to identify the differences between HRV and CRP parameters ACS patients without obtructive CAD.
It is important to group several exams: sample blood, transthoracic Doppler echocardiography (TTDE) and 24-hour Holter ECG recording.
Secondary Outcome Measures
Evaluate cardiac autonomic dysfunction associated to a systemic inflammation
To evaluate whether cardiac autonomic dysfunction is associated with low-grade systemic inflammation, inflammasome-dependent activation of IL-18 and IL-1β, and Th1/Treg frequency, in patients with ACS with or without obstructive CAD on angiography;To evaluate the precise mechanisms and molecular pathways through which cardiac autonomic dysfunction and inflammation influence each other, in order to identify possible targets for new therapeutic strategies;
Full Information
NCT ID
NCT05756452
First Posted
February 21, 2023
Last Updated
March 3, 2023
Sponsor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
1. Study Identification
Unique Protocol Identification Number
NCT05756452
Brief Title
Linking Cardiac Autonomic Dysfunction and InfLammation in Patients With Acute Coronary Syndromes
Acronym
CADILACS
Official Title
Linking Cardiac Autonomic Dysfunction and InfLammation in Patients With Acute Coronary Syndromes: a Complex Puzzle to be Solved With Potential Therapeutic Implications (CADILACS Study)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 17, 2023 (Actual)
Primary Completion Date
February 1, 2024 (Anticipated)
Study Completion Date
February 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Subclinical inflammation plays a critical role in all stages of the atherosclerotic process, from the initiation of the fatty streaks to the development of plaque instability and rupture, causing myocardial ischemia and acute coronary syndromes (ACS).
A few studies have suggested that the autonomic nervous system (ANS) and the inflammatory response are intimately linked. Accordingly, a relation between impaired cardiac autonomic tone and increased markers of inflammation has been reported in healthy subjects as well as in patients with type 1 diabetes mellitus, chronic coronary syndrome or decompensated heart failure.
To get insight in the controversial relationship between cardiac autonomic dysfunction and inflammation in patients with ACS both with and without obstructive CAD and assess the precise mechanisms and molecular pathways by which these two pathophysiological conditions mutually influence each other, to characterize their prognostic implications and identify possible targets for novel therapeutic strategies.
Detailed Description
A comprehensive assessment of cardiac autonomic function and inflammatory profile will be performed in ACS patients with obstructive CAD (n=45) or with NO-CAD (n=45) at coronary angiography. In the sub-acute phase (1 to 6 months after the ACS) all patients will undergo a global echocardiographic evaluation, a 24-hour ECG Holter recording to assess HRV and blood samples collection for neurotransmitter measurements, platelet activation and reactivity evaluation and inflammatory profile assessment by proteomics analysis, inflammasome activity evaluation, NLRP3, pro-IL-18 and pro-IL-1β expression level by qPCR and epigenetic analysis. A follow-up to establish clinical conditions of patients will be done after 12 months by direct clinical visit, trans-thoracic echocardiogram to evaluate cardiac remodeling, HRV assessment by 24-hour ECG Holter recording and blood sample collection to evaluate the inflammatory profile as it was assessed at baseline.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Coronary Syndrome, Myocardial Ischemia
Keywords
Subclinical inflammation, Autonomic nervous system, Coronary Syndrome
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Investigators will enroll partecipants who have had an acute coronary syndrome (3 months ± 15 days before enrollment) followed up at the Cardiology Unit of the participating centers.
Based on the coronary angiography results, partecipants will be divided into two groups:
patients with ACS and obstructive CAD;
patients with ACS without CAD, in a 1:1 ratio.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Partecipants with ACS and obstructive CAD
Arm Type
Experimental
Arm Description
The study is to identify a difference in the correlation between HRV and CRP parameters in ACS patients with or without obstructive CAD
Arm Title
Partecipants with ACS without CAD, in a 1:1 ratio
Arm Type
Experimental
Arm Description
Evaluate whether cardiac autonomic dysfunction is associated with low-grade systemic inflammation, inflammasome-dependent activation of IL-18 and IL-1β, and Th1/Treg frequency, in patients with ACS with or without obstructive CAD on angiography
Intervention Type
Diagnostic Test
Intervention Name(s)
Anamnesis and clinical evaluation
Other Intervention Name(s)
Transthoracic Doppler Echocardiography (TTDE);, 24-hour Holter ECG recording;, Peripheral venous blood sampling
Intervention Description
All partecipants will undergo a global echocardiographic evaluation, a 24-hour ECG Holter recording to assess HRV and blood samples collection for neurotransmitter measurements, platelet activation and reactivity evaluation and inflammatory profile assessment by proteomics analysis, inflammasome activity evaluation, NLRP3, pro-IL-18 and pro-IL-1β expression level by qPCR and epigenetic analysis.
Primary Outcome Measure Information:
Title
The correlation between HRV and CRP parameters in ACS patients with obstructive CAD
Description
The primary endpoint of the study is to identify a difference in the correlation between HRV and CRP parameters in ACS patients with or without obstructive CAD.
This study will be performed through a detailed history and clinical evaluation based on transthoracic Doppler echocardiography (TTDE) and 24-hour Holter ECG recording.
Time Frame
12 months
Title
The correlation between HRV and CRP parameters in ACS patients without obstructive CAD
Description
The study is important to identify the differences between HRV and CRP parameters ACS patients without obtructive CAD.
It is important to group several exams: sample blood, transthoracic Doppler echocardiography (TTDE) and 24-hour Holter ECG recording.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Evaluate cardiac autonomic dysfunction associated to a systemic inflammation
Description
To evaluate whether cardiac autonomic dysfunction is associated with low-grade systemic inflammation, inflammasome-dependent activation of IL-18 and IL-1β, and Th1/Treg frequency, in patients with ACS with or without obstructive CAD on angiography;To evaluate the precise mechanisms and molecular pathways through which cardiac autonomic dysfunction and inflammation influence each other, in order to identify possible targets for new therapeutic strategies;
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥18 years;
Evidence of previous complete percutaneous revascularization;
ACS, with or without CAD, experienced in the previous 3 months ±15 days;
Signed written informed consent.
Exclusion Criteria:
History of previous acute myocardial infarction (AMI);
Prior surgical myocardial revascularization via coronary artery bypass graft (CABG);
Previous incomplete percutaneous myocardial revascularization, as indicated by documentation of residual stenosis >50% or FFR ≤0.8 in any epicardial vessel;
Killip class III-IV in admission;
Established cardiovascular disease (assessed by clinical evaluation, physical exam, 12-lead ECG, or transthoracic echocardiogram), such as congenital heart disease, cardiomyopathy, and severe valvular heart disease;
Serious medical conditions, including severe renal insufficiency (eGFR > 30 ml/min), hepatic insufficiency or cirrhosis, malignancies, COPD (GOLD stage III-IV), and acute or chronic inflammatory diseases;
Refusal to sign the written informed consent to participate in the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gaetano Antonio GL Lanza
Phone
06 3015 4432
Email
gaetanoantonio.lanza@policlinicogemelli.it
Facility Information:
Facility Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS di Roma
City
Roma
State/Province
Lazio
ZIP/Postal Code
00168
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gaetano Antonio GL Lanza
Phone
06 3015 4432
Email
gaetanoantonio.lanza@policlinicogemelli.it
12. IPD Sharing Statement
Learn more about this trial
Linking Cardiac Autonomic Dysfunction and InfLammation in Patients With Acute Coronary Syndromes
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